Interaction of a magnetic island chain in a tokamak plasma with a resonant magnetic perturbation of rapidly oscillating phase

NASA Astrophysics Data System (ADS)

Fitzpatrick, Richard

2017-12-01

An investigation is made into the interaction of a magnetic island chain, embedded in a tokamak plasma, with an externally generated magnetic perturbation of the same helicity whose helical phase is rapidly oscillating. The analysis is similar in form to the classic analysis used by Kapitza [Sov. Phys. JETP 21, 588 (1951)] to examine the angular motion of a rigid pendulum whose pivot point undergoes rapid vertical oscillations. The phase oscillations are found to modify the existing terms, and also to give rise to new terms, in the equations governing the secular evolution of the island chain's radial width and helical phase. An examination of the properties of the new secular evolution equation reveals that it is possible to phase-lock an island chain to an external magnetic perturbation with an oscillating helical phase in a stabilizing phase relation provided that the amplitude, ɛ, of the phase oscillations (in radians) is such that |J0(ɛ )|≪1 , and the mean angular frequency of the perturbation closely matches the natural angular frequency of the island chain.

USSR and Eastern Europe Scientific Abstracts, Physics and Mathematics, Number 39

DTIC Science & Technology

1978-01-17

examination of a monoclinic single crystal has revealed a U022+ iön, and helical polyphosphate chains with six PO4 tetrahedra per link. Corrugated uranyl...mean mass temperature and local Nusselt number. Figures 5; references 13: 3 Russian, 10 Western. USSR UDC 535.334 DETERMINATION OF THE PARAMETERS...Nuclear Research [Abstract] The theory of pion condensation predicts the existence of super- dense nuclei, on the basis of the structure of the

The spatial configuration of ordered polynucleotide chains. II. The poly(rA) helix.

PubMed Central

Olson, W K

1975-01-01

Approximate details of the spatial configuration of the ordered single-stranded poly(rA) molecule in dilute solution have been obtained in a combined theoretical analysis of base stacking and chain flexibility. Only those regularly repeating structures which fulfill the criterion of conformational flexibility (based upon all available experimental and theoretical evidence of preferred bond rotations) and which also exhibit the right-handed base stacking pattern observed in nmr investigations of poly(rA) are deemed suitable single-stranded helices. In addition, the helical geometry of the stacked structures is required to be consistent with the experimentally observed dimensions of both completely ordered and partially ordered poly(rA) chains. Only a single category of poly(rA) helices (very similar in all conformational details to the individual chains of the poly(rA) double-stranded X-ray structure) is thus obtained. Other conformationally feasible polynucleotide helices characterized simply by a parallel and overlapping base stacking arrangement are also discussed. PMID:1052529

The Nature of Bonding in Bulk Tellurium Composed of One-Dimensional Helical Chains.

PubMed

Yi, Seho; Zhu, Zhili; Cai, Xiaolin; Jia, Yu; Cho, Jun-Hyung

2018-05-07

Bulk tellurium (Te) is composed of one-dimensional (1D) helical chains which have been considered to be coupled by van der Waals (vdW) interactions. However, on the basis of first-principles density functional theory calculations, we here propose a different bonding nature between neighboring chains: i.e., helical chains made of normal covalent bonds are connected together by coordinate covalent bonds. It is revealed that the lone pairs of electrons of Te atoms participate in forming coordinate covalent bonds between neighboring chains, where each Te atom behaves as both an electron donor to neighboring chains and an electron acceptor from neighboring chains. This ligand-metal-like bonding nature in bulk Te results in the same order of bulk moduli along the directions parallel and perpendicular to the chains, contrasting with the large anisotropy of bulk moduli in vdW crystals. We further find that the electron effective masses parallel and perpendicular to the chains are almost the same as each other, consistent with the observed nearly isotropic electrical resistivity. It is thus demonstrated that the normal/coordinate covalent bonds parallel/perpendicular to the chains in bulk Te lead to a minor anisotropy in structural and transport properties.

Automated main-chain model building by template matching and iterative fragment extension.

PubMed

Terwilliger, Thomas C

2003-01-01

An algorithm for the automated macromolecular model building of polypeptide backbones is described. The procedure is hierarchical. In the initial stages, many overlapping polypeptide fragments are built. In subsequent stages, the fragments are extended and then connected. Identification of the locations of helical and beta-strand regions is carried out by FFT-based template matching. Fragment libraries of helices and beta-strands from refined protein structures are then positioned at the potential locations of helices and strands and the longest segments that fit the electron-density map are chosen. The helices and strands are then extended using fragment libraries consisting of sequences three amino acids long derived from refined protein structures. The resulting segments of polypeptide chain are then connected by choosing those which overlap at two or more C(alpha) positions. The fully automated procedure has been implemented in RESOLVE and is capable of model building at resolutions as low as 3.5 A. The algorithm is useful for building a preliminary main-chain model that can serve as a basis for refinement and side-chain addition.

Drill drive mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dressel, M.O.

1979-10-30

A drill drive mechanism is especially adapted to provide both rotational drive and axial feed for a drill of substantial diameter such as may be used for drilling holes for roof bolts in mine shafts. The drill shaft is made with a helical pattern of scroll-like projections on its surface for removal of cuttings. The drill drive mechanism includes a plurality of sprockets carrying two chains of drive links which are arranged to interlock around the drill shaft with each drive link having depressions which mate with the scroll-like projections. As the chain links move upwardly or downwardly the surfacesmore » of the depressions in the links mate with the scroll projections to move the shaft axially. Tangs on the drive links mate with notch surfaces between scroll projections to provide a means for rotating the shaft. Projections on the drive links mate together at the center to hold the drive links tightly around the drill shaft. The entire chain drive mechanism is rotated around the drill shaft axis by means of a hydraulic motor and gear drive to cause rotation of the drill shaft. This gear drive also connects with a differential gearset which is interconnected with a second gear. A second motor is connected to the spider shaft of the different gearset to produce differential movement (speeds) at the output gears of the differential gearset. This differential in speed is utilized to drive said second gear at a speed different from the speed of said gear drive, this speed differential being utilized to drive said sprockets for axial movement of said drill shaft. 11 claims.« less

Drill drive mechanism

DOEpatents

Dressel, Michael O.

1979-01-01

A drill drive mechanism is especially adapted to provide both rotational drive and axial feed for a drill of substantial diameter such as may be used for drilling holes for roof bolts in mine shafts. The drill shaft is made with a helical pattern of scroll-like projections on its surface for removal of cuttings. The drill drive mechanism includes a plurality of sprockets carrying two chains of drive links which are arranged to interlock around the drill shaft with each drive link having depressions which mate with the scroll-like projections. As the chain links move upwardly or downwardly the surfaces of the depressions in the links mate with the scroll projections to move the shaft axially. Tangs on the drive links mate with notch surfaces between scroll projections to provide a means for rotating the shaft. Projections on the drive links mate together at the center to hold the drive links tightly around the drill shaft. The entire chain drive mechanism is rotated around the drill shaft axis by means of a hydraulic motor and gear drive to cause rotation of the drill shaft. This gear drive also connects with a differential gearset which is interconnected with a second gear. A second motor is connected to the spider shaft of the differential gearset to produce differential movement (speeds) at the output gears of the differential gearset. This differential in speed is utilized to drive said second gear at a speed different from the speed of said gear drive, this speed differential being utilized to drive said sprockets for axial movement of said drill shaft.

Control of Helical Chirality of Ferrocene-Dipeptide Conjugates by the Secondary Structure of Dipeptide Chains.

PubMed

Moriuchi, Toshiyuki; Nishiyama, Taiki; Nobu, Masaki; Hirao, Toshikazu

2017-09-18

Controlling helical chirality and creating protein secondary structures in cyclic/acyclic ferrocene-dipeptide bioorganometallic conjugates were achieved by adjusting the conformational flexibility of the dipeptide chains. In systems reported to date, the helical chirality of a conjugate was determined by the absolute configuration of the adjacent amino acid reside. In contrast, it was possible to induce both M- and P-helical chirality, even when the configuration of the adjacent amino acid was the same. It is particularly interesting to note that M-helical chirality was produced in a cyclic ferrocene-dipeptide conjugate composed of the l-Ala-d-Pro-cystamine-d-Pro-l-Ala dipeptide sequence (1), in which a type II β-turn-like secondary structure was established. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

C-peptide inhibitors of Ebola virus glycoprotein-mediated cell entry: effects of conjugation to cholesterol and side chain-side chain crosslinking.

PubMed

Higgins, Chelsea D; Koellhoffer, Jayne F; Chandran, Kartik; Lai, Jonathan R

2013-10-01

We previously described potent inhibition of Ebola virus entry by a 'C-peptide' based on the GP2 C-heptad repeat region (CHR) targeted to endosomes ('Tat-Ebo'). Here, we report the synthesis and evaluation of C-peptides conjugated to cholesterol, and Tat-Ebo analogs containing covalent side chain-side chain crosslinks to promote α-helical conformation. We found that the cholesterol-conjugated C-peptides were potent inhibitors of Ebola virus glycoprotein (GP)-mediated cell entry (~10(3)-fold reduction in infection at 40 μM). However, this mechanism of inhibition is somewhat non-specific because the cholesterol-conjugated peptides also inhibited cell entry mediated by vesicular stomatitis virus glycoprotein G. One side chain-side chain crosslinked peptide had moderately higher activity than the parent compound Tat-Ebo. Circular dichroism revealed that the cholesterol-conjugated peptides unexpectedly formed a strong α-helical conformation that was independent of concentration. Side chain-side chain crosslinking enhanced α-helical stability of the Tat-Ebo variants, but only at neutral pH. These result provide insight into mechanisms of C-peptide inhibiton of Ebola virus GP-mediated cell entry. Copyright © 2013 Elsevier Ltd. All rights reserved.

Helicity of short E-R/K peptides.

PubMed

Sommese, Ruth F; Sivaramakrishnan, Sivaraj; Baldwin, Robert L; Spudich, James A

2010-10-01

Understanding the secondary structure of peptides is important in protein folding, enzyme function, and peptide-based drug design. Previous studies of synthetic Ala-based peptides (>12 a.a.) have demonstrated the role for charged side chain interactions involving Glu/Lys or Glu/Arg spaced three (i, i + 3) or four (i, i + 4) residues apart. The secondary structure of short peptides (<9 a.a.), however, has not been investigated. In this study, the effect of repetitive Glu/Lys or Glu/Arg side chain interactions, giving rise to E-R/K helices, on the helicity of short peptides was examined using circular dichroism. Short E-R/K-based peptides show significant helix content. Peptides containing one or more E-R interactions display greater helicity than those with similar E-K interactions. Significant helicity is achieved in Arg-based E-R/K peptides eight, six, and five amino acids long. In these short peptides, each additional i + 3 and i + 4 salt bridge has substantial contribution to fractional helix content. The E-R/K peptides exhibit a strongly linear melt curve indicative of noncooperative folding. The significant helicity of these short peptides with predictable dependence on number, position, and type of side chain interactions makes them an important consideration in peptide design.

Synthesis, crystallographic and spectral studies of homochiral cobalt(II) and nickel(II) complexes of a new terpyridylaminoacid ligand

NASA Astrophysics Data System (ADS)

Wang, Xing; Gao, Chang-Qing; Gao, Zhi-Yang; Wu, Ben-Lai; Niu, Yun-Yin

2018-04-01

Based on a chiral terpyridylaminoacid ligand, a series of homochiral Co(II) and Ni(II) complexes, namely, [Co(H2L)(HL)]·Cl·(PF6)2·2H2O (1), [Ni(H2L)(HL)]·Cl·(PF6)2 (2), [Co2(L)2(CH3OH)(H2O)]·(PF6)2·CH3OH (3), [Ni2(L)2(CH3OH)2]·(PF6)2·2CH3OH (4), [Co2(L)2(N3)2]·3H2O (5), and [Ni2(L)2(SCN)2]·4H2O (6) have been successfully synthesized and characterized by elemental analysis, TGA, spectroscopic methods (IR, CD and electronic absorption spectra) and single-crystal X-ray diffraction structural analysis (HL = (S)-2-((4-([2,2':6‧,2″-terpyridin]-4‧-yl)benzyl)amino)-4-methylpentanoic acid). In the acidic reaction conditions, one protonated (H2L)+ and one zwitterionic HL only used their terpyridyl groups to chelate one metal ion Co(II) or Ni(II), forming chiral mononuclear cationic complexes 1 or 2. But in the basic and hydro(solvo)thermal reaction conditions, deprotonated ligands (L)‒ acting as bridges used their terpyridyl and amino acid groups to link with two Co(II) or Ni(II) ions, fabricating chiral dinuclear metallocyclic complexes 3-6. Those chiral mononuclear and dinuclear complexes whose chirality originates in the homochiral ligand HL further self-assemble into higher-dimensional homochiral supramolecular frameworks through intermolecular hydrogen-bonding and π···π interactions. Notably, the coordination mode, hydrogen-bonding site, and existence form of HL ligand can be controlled by the protonation of its amino group, and the architectural diversity of those supramolecular frameworks is adjusted by pH and counter anions. Very interestingly, the 3D porous supramolecular frameworks built up from the huge chiral mononuclear cationic complexes 1 and 2 have novel helical layers only formed through every right-handed helical chain intertwining with two adjacent same helical chains, and the 2D supramolecular helicate 5 consists of two types of left-handed helical chains.

The solubilization of bone and dentin collagens by pepsin. Effect of cross-linkages and non-collagen components.

PubMed

Carmichael, D J; Dodd, C M; Veis, A

1977-03-28

Bone and dentin collagen are less susceptible to solubilization by pepsin digestion then is skin collagen. Digestion at 4 degrees C for 72 h solubilized only 35.3% of bovine cortical bone and 5.6% of bovine dentin compared with nearly 100% dissolution of bovine skin. Sodium dodecyl sulfate-acrylamide gel electrophoresis and molecular sieve chromatography showed that, for bone and dentin, intact alpha chains and cross-linked aggregates of beta, gamma and higher weight remained intact after pepsin solubilization but lower molecular weight fragments also were prevalent indicating chain scission in helical regions. Electron microscopic examination of segment long spacing precipitates of the soluble collagens confirmed the presence of solubilized polymerized collagen. The principal reducible cross-link in both bone and dentin was the precursor of dihydroxylsinonorleucine and this cross-link was also present in the solubilized collagens. Small amounts of non-collagenous proteins and glycosaminoglycans of different compositions in dentin and bone resisted extraction before pepsin digestion. However, the differences in solubilization of the collagens have been related to differences in cross-linkage placement.

Helical Inversion of Gel Fibrils by Elongation of Perfluoroalkyl Chains as Studied by Vibrational Circular Dichroism.

PubMed

Sato, Hisako; Yajima, Tomoko; Yamagishi, Akihiko

2016-05-01

Vibrational circular dichroism (VCD) spectroscopy was applied to gelation by a chiral low-molecular mass weight gelator, N,N'-diperfluoroalkanoyl-1,2-trans-diaminocyclohexane. Attention was focused on the winding effects of (-CF2 )n chains on the gelating ability. For this purpose, a series of gelators were synthesized with perfluoroalkyl chains of different length (n = 6-8). When gelation was studied using acetonitrile as a solvent, the fibrils took different morphologies, depending on the chain length: twisted saddle-like ribbon or helical ribbon from fibril (n = 6) and a helical ribbon from platelet (n = 8). The signs of VCD peaks assigned to the couplet of C=O stretching and to the C-F stretching were also dependent on n, indicating that a gelator molecule changed conformation on elongating perfluoroalkyl chains. A model is proposed for the aggregation modes in fibrils. Chirality 28:361-364, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Alpha-helix to beta-sheet transition in long-chain poly-l-lysine: Formation of alpha-helical fibrils by poly-l-lysine.

PubMed

Cieślik-Boczula, Katarzyna

2017-06-01

The temperature-induced α-helix to β-sheet transition in long-chain poly-l-lysine (PLL), accompanied by the gauche-to-trans isomerization of CH 2 groups in the hydrocarbon side chains of Lys amino acid residues, and formation of β-sheet as well as α-helix fibrillar aggregates of PLL have been studied using Fourier-transform infrared (FT-IR) and vibrational circular dichroism (VCD) spectroscopy, and transmission electron microscopy (TEM). In a low-temperature alkaline water solution or in a methanol-rich water mixture, the secondary structure of PLL is represented by α-helical conformations with unordered and gauche-rich hydrocarbon side chains. Under these conditions, PLL molecules aggregate into α-helical fibrils. PLLs dominated by extended antiparallel β-sheet structures with highly ordered trans-rich hydrocarbon side chains are formed in a high-temperature range at alkaline pD and aggregate into fibrillar, protofibrillar, and spherical forms. Presented data support the idea that fibrillar aggregation is a varied phenomenon possible in repetitive structural elements with not only a β-sheet-rich conformation, but also an α-helical-rich conformation. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Magnetic helices as metastable states of finite XY ferromagnetic chains: An analytical study

NASA Astrophysics Data System (ADS)

Popov, Alexander P.; Pini, Maria Gloria

2018-04-01

We investigated a simple but non trivial model, consisting of a chain of N classical XY spins with nearest neighbor ferromagnetic interaction, where each of the two end-point spins is assumed to be exchange-coupled to a fully-pinned fictitious spin. In the mean field approximation, the system might be representative of a soft ferromagnetic film sandwiched between two magnetically hard layers. We show that, while the ground state is ferromagnetic and collinear, the system can attain non-collinear metastable states in the form of magnetic helices. The helical solutions and their stability were studied analytically in the absence of an external magnetic field. There are four possible classes of solutions. Only one class is metastable, and its helical states contain an integer number of turns. Among the remaining unstable classes, there is a class of helices which contain an integer number of turns. Therefore, an integer number of turns in a helical configuration is a necessary, but not a sufficient, condition for metastability. These results may be useful to devise future applications of metastable magnetic helices as energy-storing elements.

Electrostatic bending response of a charged helix

NASA Astrophysics Data System (ADS)

Zampetaki, A. V.; Stockhofe, J.; Schmelcher, P.

2018-04-01

We explore the electrostatic bending response of a chain of charged particles confined on a finite helical filament. We analyze how the energy difference Δ E between the bent and the unbent helical chain scales with the length of the helical segment and the radius of curvature and identify features that are not captured by the standard notion of the bending rigidity, normally used as a measure of bending tendency in the linear response regime. Using Δ E to characterize the bending response of the helical chain we identify two regimes with qualitatively different bending behaviors for the ground state configuration: the regime of small and the regime of large radius-to-pitch ratio, respectively. Within the former regime, Δ E changes smoothly with the variation of the system parameters. Of particular interest are its oscillations with the number of charged particles encountered for commensurate fillings which yield length-dependent oscillations in the preferred bending direction of the helical chain. We show that the origin of these oscillations is the nonuniformity of the charge distribution caused by the long-range character of the Coulomb interactions and the finite length of the helix. In the second regime of large values of the radius-to-pitch ratio, sudden changes in the ground state structure of the charges occur as the system parameters vary, leading to complex and discontinuous variations in the ground state bending response Δ E .

Crystal structure of N-(1-allyl-3-chloro-4-eth-oxy-1H-indazol-5-yl)-4-meth-oxybenzene-sulfonamide.

PubMed

Chicha, Hakima; Rakib, El Mostapha; Bouissane, Latifa; Saadi, Mohamed; El Ammari, Lahcen

2014-09-01

In the title compound, C19H20ClN3O4S, the benzene ring is inclined to the indazole ring system (r.m.s. deviation = 0.014 Å) by 65.07 (8)°. The allyl and eth-oxy groups are almost normal to the indazole ring, as indicated by the respective torsion angles [N-N-C-C = 111.6 (2) and C-C-O-C = -88.1 (2)°]. In the crystal, mol-ecules are connected by N-H⋯N hydrogen bonds, forming helical chains propagating along [010]. The chains are linked by C-H⋯O hydrogen bonds, forming a three-dimensional network.

A rare polyglycine type II-like helix motif in naturally occurring proteins.

PubMed

Warkentin, Eberhard; Weidenweber, Sina; Schühle, Karola; Demmer, Ulrike; Heider, Johann; Ermler, Ulrich

2017-11-01

Common structural elements in proteins such as α-helices or β-sheets are characterized by uniformly repeating, energetically favorable main chain conformations which additionally exhibit a completely saturated hydrogen-bonding network of the main chain NH and CO groups. Although polyproline or polyglycine type II helices (PP II or PG II ) are frequently found in proteins, they are not considered as equivalent secondary structure elements because they do not form a similar self-contained hydrogen-bonding network of the main chain atoms. In this context our finding of an unusual motif of glycine-rich PG II -like helices in the structure of the acetophenone carboxylase core complex is of relevance. These PG II -like helices form hexagonal bundles which appear to fulfill the criterion of a (largely) saturated hydrogen-bonding network of the main-chain groups and therefore may be regarded in this sense as a new secondary structure element. It consists of a central PG II -like helix surrounded by six nearly parallel PG II -like helices in a hexagonal array, plus an additional PG II -like helix extending the array outwards. Very related structural elements have previously been found in synthetic polyglycine fibers. In both cases, all main chain NH and CO groups of the central PG II -helix are saturated by either intra- or intermolecular hydrogen-bonds, resulting in a self-contained hydrogen-bonding network. Similar, but incomplete PG II -helix patterns were also previously identified in a GTP-binding protein and an antifreeze protein. © 2017 Wiley Periodicals, Inc.

Helicity conservation by flow across scales in reconnecting vortex links and knots

PubMed Central

Scheeler, Martin W.; Kleckner, Dustin; Kindlmann, Gordon L.; Irvine, William T. M.

2014-01-01

The conjecture that helicity (or knottedness) is a fundamental conserved quantity has a rich history in fluid mechanics, but the nature of this conservation in the presence of dissipation has proven difficult to resolve. Making use of recent advances, we create vortex knots and links in viscous fluids and simulated superfluids and track their geometry through topology-changing reconnections. We find that the reassociation of vortex lines through a reconnection enables the transfer of helicity from links and knots to helical coils. This process is remarkably efficient, owing to the antiparallel orientation spontaneously adopted by the reconnecting vortices. Using a new method for quantifying the spatial helicity spectrum, we find that the reconnection process can be viewed as transferring helicity between scales, rather than dissipating it. We also infer the presence of geometric deformations that convert helical coils into even smaller scale twist, where it may ultimately be dissipated. Our results suggest that helicity conservation plays an important role in fluids and related fields, even in the presence of dissipation. PMID:25326419

Cross-Linking Studies of Lysozyme Nucleation

NASA Technical Reports Server (NTRS)

Forsythe, Elizabeth; Pusey, Marc

2000-01-01

Tetragonal chicken egg white crystals consist of 4(sub 3) helices running in alternating directions, the helix rows having a two fold symmetry with each other. The unit cell consists of one complete tetrameric turn from each of two adjacent helices (an octamer). PBC analysis indicates that the helix intermolecular bonds are the strongest in the crystal, therefore likely formed first. AFM analysis of the (110) surface shows only complete helices, no half steps or bisected helices being found, while AFM line scans to measure the growth step increments show that they are multiples of the 4(sub 3) helix tetramer dimensions. This supports our thesis that the growth units are in fact multiples of the four molecule 4(sub 3) helix unit, the "average" growth unit size for the (110) face being an octamer (two turns about the helix) and the (101) growth unit averaging about the size of a hexamer. In an effort to better understand the species involved in the crystal nucleation and growth process, we have initiated an experimental program to study the species formed in solution compared to what is found in the crystal through covalent cross-linking studies. These experiments use the heterobifunctional cross-linking agent aminoethyl-4-azidonitroanaline (AEANA). An aliphatic amine at one end is covalently attached to the protein by a carbodiimide-mediated reaction, and a photo reactive group at the other can be used to initiate crosslinking. Modifications to the parent structure can be used to alter the distance between the two reactive groups and thus the cross-linking agents "reach". In practice, the cross-linking agent is first coupled to the asp101 side chain through the amine group. Asp101 lies within the active site cleft, and previous work with fluorescent probes had shown that derivatives at this site still crystallize in the tetragonal space group. This was also found to be the case with the AEANA derivative, which gave red tetragonal crystals. The protein now has a reactive group that can be photoactivated at a specific point in the nucleation or crystal growth process to "capture" protein molecules bound within reach of the crosslinking agent. If those bound protein molecules have a defined geometric relationship with the capturing molecule, such as would be found in a crystal, then the photoreacted cross-linking site should be consistent. Random protein interactions, typical of an amorphous precipitate or interaction, would show a random cross-linking reaction. The results of these and other experiments will be presented.

Transferability of different classical force fields for right and left handed α-helices constructed from enantiomeric amino acids.

PubMed

Biswas, Santu; Sarkar, Sujit; Pandey, Prithvi Raj; Roy, Sudip

2016-02-21

Amino acids can form d and l enantiomers, of which the l enantiomer is abundant in nature. The naturally occurring l enantiomer has a greater preference for a right handed helical conformation, and the d enantiomer for a left handed helical conformation. The other conformations, that is, left handed helical conformations of the l enantiomers and right handed helical conformations of the d enantiomers, are not common. The energetic differences between left and right handed alpha helical peptide chains constructed from enantiomeric amino acids are investigated using quantum chemical calculations (using the M06/6-311g(d,p) level of theory). Further, the performances of commonly used biomolecular force fields (OPLS/AA, CHARMM27/CMAP and AMBER) to represent the different helical conformations (left and right handed) constructed from enantiomeric (D and L) amino acids are evaluated. 5- and 10-mer chains from d and l enantiomers of alanine, leucine, lysine, and glutamic acid, in right and left handed helical conformations, are considered in the study. Thus, in total, 32 α-helical polypeptides (4 amino acids × 4 conformations of 5-mer and 10-mer) are studied. Conclusions, with regards to the performance of the force fields, are derived keeping the quantum optimized geometry as the benchmark, and on the basis of phi and psi angle calculations, hydrogen bond analysis, and different long range helical order parameters.

Flow-through polymerase chain reaction inside a seamless 3D helical microreactor fabricated utilizing a silicone tube and a paraffin mold.

PubMed

Wu, Wenming; Trinh, Kieu The Loan; Lee, Nae Yoon

2015-03-07

We introduce a new strategy for fabricating a seamless three-dimensional (3D) helical microreactor utilizing a silicone tube and a paraffin mold. With this method, various shapes and sizes of 3D helical microreactors were fabricated, and a complicated and laborious photolithographic process, or 3D printing, was eliminated. With dramatically enhanced portability at a significantly reduced fabrication cost, such a device can be considered to be the simplest microreactor, developed to date, for performing the flow-through polymerase chain reaction (PCR).

Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I.

PubMed

Peisley, Alys; Wu, Bin; Xu, Hui; Chen, Zhijian J; Hur, Sun

2014-05-01

Ubiquitin (Ub) has important roles in a wide range of intracellular signalling pathways. In the conventional view, ubiquitin alters the signalling activity of the target protein through covalent modification, but accumulating evidence points to the emerging role of non-covalent interaction between ubiquitin and the target. In the innate immune signalling pathway of a viral RNA sensor, RIG-I, both covalent and non-covalent interactions with K63-linked ubiquitin chains (K63-Ubn) were shown to occur in its signalling domain, a tandem caspase activation and recruitment domain (hereafter referred to as 2CARD). Non-covalent binding of K63-Ubn to 2CARD induces its tetramer formation, a requirement for downstream signal activation. Here we report the crystal structure of the tetramer of human RIG-I 2CARD bound by three chains of K63-Ub2. 2CARD assembles into a helical tetramer resembling a 'lock-washer', in which the tetrameric surface serves as a signalling platform for recruitment and activation of the downstream signalling molecule, MAVS. Ubiquitin chains are bound along the outer rim of the helical trajectory, bridging adjacent subunits of 2CARD and stabilizing the 2CARD tetramer. The combination of structural and functional analyses reveals that binding avidity dictates the K63-linkage and chain-length specificity of 2CARD, and that covalent ubiquitin conjugation of 2CARD further stabilizes the Ub-2CARD interaction and thus the 2CARD tetramer. Our work provides unique insights into the novel types of ubiquitin-mediated signal-activation mechanism, and previously unexpected synergism between the covalent and non-covalent ubiquitin interaction modes.

Properties of polyproline II, a secondary structure element implicated in protein-protein interactions.

PubMed

Cubellis, M V; Caillez, F; Blundell, T L; Lovell, S C

2005-03-01

The polyproline II (PPII) conformation of protein backbone is an important secondary structure type. It is unusual in that, due to steric constraints, its main-chain hydrogen-bond donors and acceptors cannot easily be satisfied. It is unable to make local hydrogen bonds, in a manner similar to that of alpha-helices, and it cannot easily satisfy the hydrogen-bonding potential of neighboring residues in polyproline conformation in a manner analogous to beta-strands. Here we describe an analysis of polyproline conformations using the HOMSTRAD database of structurally aligned proteins. This allows us not only to determine amino acid propensities from a much larger database than previously but also to investigate conservation of amino acids in polyproline conformations, and the conservation of the conformation itself. Although proline is common in polyproline helices, helices without proline represent 46% of the total. No other amino acid appears to be greatly preferred; glycine and aromatic amino acids have low propensities for PPII. Accordingly, the hydrogen-bonding potential of PPII main-chain is mainly satisfied by water molecules and by other parts of the main-chain. Side-chain to main-chain interactions are mostly nonlocal. Interestingly, the increased number of nonsatisfied H-bond donors and acceptors (as compared with alpha-helices and beta-strands) makes PPII conformers well suited to take part in protein-protein interactions. Copyright 2005 Wiley-Liss, Inc.

Structure-activity relationship study of Aib-containing amphipathic helical peptide-cyclic RGD conjugates as carriers for siRNA delivery.

PubMed

Wada, Shun-Ichi; Takesada, Anna; Nagamura, Yurie; Sogabe, Eri; Ohki, Rieko; Hayashi, Junsuke; Urata, Hidehito

2017-12-15

The conjugation of Aib-containing amphipathic helical peptide with cyclo(-Arg-Gly-Asp-d-Phe-Cys-) (cRGDfC) at the C-terminus of the helix peptide (PI) has been reported to be useful for constructing a carrier for targeted siRNA delivery into cells. In order to explore structure-activity relationships for the development of potential carriers for siRNA delivery, we synthesized conjugates of Aib-containing amphipathic helical peptide with cRGDfC at the N-terminus (PII) and both the N- and C-termini (PIII) of the helical peptide. Furthermore, to examine the influence of PI helical chain length on siRNA delivery, truncated peptides containing 16 (PIV), 12 (PV), and 8 (PVI) amino acid residues at the N-terminus of the helical chain were synthesized. PII and PIII, as well as PI, could deliver anti-luciferase siRNA into cells to induce the knockdown of luciferase stably expressed in cells. In contrast, all of the truncated peptides were unlikely to transport siRNA into cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Small differences in amylopectin fine structure may explain large functional differences of starch.

PubMed

Bertoft, Eric; Annor, George A; Shen, Xinyu; Rumpagaporn, Pinthip; Seetharaman, Koushik; Hamaker, Bruce R

2016-04-20

Four amylose-free waxy rice starches were found to give rise to gels with clearly different morphology after storage for seven days at 4°C. The thermal and rheological properties of these gels were also different. This was remarkable in light of the subtle differences in the molecular structure of the amylopectin in the samples. Addition of iodine to the amylopectin samples suggested that not only external chains, but also the internal chains of amylopectin, could form helical inclusion complexes. It is suggested that these internal helical segments participate in the retrogradation of amylopectin, thereby stabilising the gels through double helical structures with external chains of adjacent molecules. Albeit few in number, such interactions appear to have important influences on starch functional properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

An auto-inhibitory helix in CTP:phosphocholine cytidylyltransferase hijacks the catalytic residue and constrains a pliable, domain-bridging helix pair

PubMed Central

Ramezanpour, Mohsen; Lee, Jaeyong; Taneva, Svetla G.; Tieleman, D. Peter; Cornell, Rosemary B.

2018-01-01

The activity of CTP:phosphocholine cytidylyltransferase (CCT), a key enzyme in phosphatidylcholine synthesis, is regulated by reversible interactions of a lipid-inducible amphipathic helix (domain M) with membrane phospholipids. When dissociated from membranes, a portion of the M domain functions as an auto-inhibitory (AI) element to suppress catalysis. The AI helix from each subunit binds to a pair of α helices (αE) that extend from the base of the catalytic dimer to create a four-helix bundle. The bound AI helices make intimate contact with loop L2, housing a key catalytic residue, Lys122. The impacts of the AI helix on active-site dynamics and positioning of Lys122 are unknown. Extensive MD simulations with and without the AI helix revealed that backbone carbonyl oxygens at the point of contact between the AI helix and loop L2 can entrap the Lys122 side chain, effectively competing with the substrate, CTP. In silico, removal of the AI helices dramatically increased αE dynamics at a predicted break in the middle of these helices, enabling them to splay apart and forge new contacts with loop L2. In vitro cross-linking confirmed the reorganization of the αE element upon membrane binding of the AI helix. Moreover, when αE bending was prevented by disulfide engineering, CCT activation by membrane binding was thwarted. These findings suggest a novel two-part auto-inhibitory mechanism for CCT involving capture of Lys122 and restraint of the pliable αE helices. We propose that membrane binding enables bending of the αE helices, bringing the active site closer to the membrane surface. PMID:29519816

Crystal structure of N-(1-allyl-3-chloro-4-eth­oxy-1H-indazol-5-yl)-4-meth­oxybenzene­sulfonamide

PubMed Central

Chicha, Hakima; Rakib, El Mostapha; Bouissane, Latifa; Saadi, Mohamed; El Ammari, Lahcen

2014-01-01

In the title compound, C19H20ClN3O4S, the benzene ring is inclined to the indazole ring system (r.m.s. deviation = 0.014 Å) by 65.07 (8)°. The allyl and eth­oxy groups are almost normal to the indazole ring, as indicated by the respective torsion angles [N—N—C—C = 111.6 (2) and C—C—O—C = −88.1 (2)°]. In the crystal, mol­ecules are connected by N—H⋯N hydrogen bonds, forming helical chains propagating along [010]. The chains are linked by C—H⋯O hydrogen bonds, forming a three-dimensional network. PMID:25309208

The Packing of Helical and Zigzag Chains and Distribution of Interstitial Voids in Expanded Liquid Se near the Semiconductor to Metal Transition

NASA Astrophysics Data System (ADS)

Maruyama, Kenji; Hiroi (Sato), Satoshi; Endo, Hirohisa; Hoshino, Hideoki; Odagaki, Takashi; Hensel, Friedrich

2017-08-01

The reverse Monte Carlo (RMC) and Voronoi-Delaunay (VD) void analyses were applied to study the modification of chain geometries near the semiconductor (SC) to metal (M) transition in expanded liquid Se along the isochore of d = 3.4 g/cm3. Fluctuations of dihedral angles with increasing temperature and pressure cause modification of the helical (H) chain to the planar zigzag (Z) chain conformations. The distribution of voids size (rV ) supported by chain segments and distances to the 4th 6th neighbor atoms on the chain segments provide information on the stacking of planar zigzag chains compensated by empty space (L-voids, rV 3.6 Å) which leads to the formation of metallic domains. Near SC-M transition region the number fraction NZ/NH for Z and H chain segments increases.

Stabilizing interactions between aromatic and basic side chains in alpha-helical peptides and proteins. Tyrosine effects on helix circular dichroism.

PubMed

Andrew, Charles D; Bhattacharjee, Samita; Kokkoni, Nicoleta; Hirst, Jonathan D; Jones, Gareth R; Doig, Andrew J

2002-10-30

Here we investigate the structures and energetics of interactions between aromatic (Phe or Tyr) and basic (Lys or Arg) amino acids in alpha-helices. Side chain interaction energies are measured using helical peptides, by quantifying their helicities with circular dichroism at 222 nm and interpreting the results with Lifson-Roig-based helix/coil theory. A difficulty in working with Tyr is that the aromatic ring perturbs the CD spectrum, giving an incorrect helicity. We calculated the effect of Tyr on the CD at 222 nm by deriving the intensities of the bands directly from the electronic and magnetic transition dipole moments through the rotational strengths corresponding to each excited state of the polypeptide. This gives an improved value of the helix preference of Tyr (from 0.48 to 0.35) and a correction to the helicity for the peptides containing Tyr. We find that Phe-Lys, Lys-Phe, Phe-Arg, Arg-Phe, and Tyr-Lys are all stabilizing by -0.10 to -0.18 kcal.mol-1 when placed i, i + 4 on the surface of a helix in aqueous solution, despite the great difference in polarity between these residues. Interactions between these side chains have previously been attributed to cation-pi bonds. A survey of protein structures shows that they are in fact predominantly hydrophobic interactions between the CH2 groups of Lys or Arg and the aromatic rings.

Supramolecular Organization of the α121-α565 Collagen IV Network*

PubMed Central

Robertson, Wesley E.; Rose, Kristie L.; Hudson, Billy G.; Vanacore, Roberto M.

2014-01-01

Collagen IV is a family of 6 chains (α1-α6), that form triple-helical protomers that assemble into supramolecular networks. Two distinct networks with chain compositions of α121 and α345 have been established. These oligomerize into separate α121 and α345 networks by a homotypic interaction through their trimeric noncollagenous (NC1) domains, forming α121 and α345 NC1 hexamers, respectively. These are stabilized by novel sulfilimine (SN) cross-links, a covalent cross-link that forms between Met93 and Hyl211 at the trimer-trimer interface. A third network with a composition of α1256 has been proposed, but its supramolecular organization has not been established. In this study we investigated the supramolecular organization of this network by determining the chain identity of sulfilimine-cross-linked NC1 domains derived from the α1256 NC1 hexamer. High resolution mass spectrometry analyses of peptides revealed that sulfilimine bonds specifically cross-link α1 to α5 and α2 to α6 NC1 domains, thus providing the spatial orientation between interacting α121 and α565 trimers. Using this information, we constructed a three-dimensional homology model in which the α565 trimer shows a good chemical and structural complementarity to the α121 trimer. Our studies provide the first chemical evidence for an α565 protomer and its heterotypic interaction with the α121 protomer. Moreover, our findings, in conjunction with our previous studies, establish that the six collagen IV chains are organized into three canonical protomers α121, α345, and α565 forming three distinct networks: α121, α345, and α121-α565, each of which is stabilized by sulfilimine bonds between their C-terminal NC1 domains. PMID:25006246

Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS)☟

PubMed Central

Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M.; Ioerger, Thomas R.; Burgess, Kevin

2013-01-01

Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, “minimalist helical mimics”. It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i+4, i+7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i+3, i+7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds;(iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain “triads” in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the “side-chain correspondences” (eg i, i+4, i+7 or i, i+3, i+4) of those overlays, and the energy of this state relative to the minimum located. This protocol was tested on some of the most widely cited minimalist α-helical mimics (1 – 8 in the text). The data obtained indicates several of these compounds preferentially exist in conformations that resemble other secondary structures as well as α-helices, and many of the α-helical conformations have unexpected side-chain correspondences. These observations imply the featured minimalist mimics have more scope for disrupting PPI interfaces than previously anticipated. Finally, the same simulation method was used to match preferred conformations of minimalist mimics with actual protein/peptide structures at interfaces providing quantitative comparisons of predicted fits of the test mimics at protein-protein interaction sites. PMID:24121516

Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS).

PubMed

Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M; Ioerger, Thomas R; Burgess, Kevin

2013-11-28

Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, "minimalist helical mimics". It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i + 4, i + 7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i + 3, i + 7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; (iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain "triads" in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the "side-chain correspondences" (e.g. i, i + 4, i + 7 or i, i + 3, i + 4) of those overlays, and the energy of this state relative to the minimum located. This protocol was tested on some of the most widely cited minimalist α-helical mimics (1-8 in the text). The data obtained indicates several of these compounds preferentially exist in conformations that resemble other secondary structures as well as α-helices, and many of the α-helical conformations have unexpected side-chain correspondences. These observations imply the featured minimalist mimics have more scope for disrupting PPI interfaces than previously anticipated. Finally, the same simulation method was used to match preferred conformations of minimalist mimics with actual protein/peptide structures at interfaces providing quantitative comparisons of predicted fits of the test mimics at protein-protein interaction sites.

Synthesis, structure, and magnetic properties of two 1-D helical coordination polymeric Cu(II) complexes

NASA Astrophysics Data System (ADS)

Bian, He-Dong; Yang, Xiao-E.; Yu, Qing; Chen, Zi-Lu; Liang, Hong; Yan, Shi-Ping; Liao, Dai-Zheng

2008-01-01

Two helical coordination polymeric copper(II) complexes bearing amino acid Schiff bases HL or HL', which are condensed from 2-hydroxy-1-naphthaldehyde with 2-aminobenzoic acid or L-valine, respectively, have been prepared and characterised by X-ray crystallography. In [CuL] n ( 1) the copper(II) atoms are bridged by syn- anti carboxylate groups giving infinite 1-D right-handed helical chains which are further connected by weak C-H⋯Cu interactions to build a 2-D network. While in [CuL'] n ( 2) the carboxylate group acts as a rare monatomic bridge to connect the adjacent copper(II) atoms leading to the formation of a left-handed helical chain. Magnetic susceptibility measurements indicate that 1 exhibits weak ferromagnetic interactions whereas an antiferromagnetic coupling is established for 2. The magnetic behavior can be satisfactorily explained on the basis of the structural data.

The dominant role of side chains in supramolecular double helical organisation in synthetic tripeptides

NASA Astrophysics Data System (ADS)

Sharma, Ankita; Tiwari, Priyanka; Dutt Konar, Anita

2018-06-01

Peptide self-assembled nanostructures have attracted attention recently owing to their promising applications in diversified avenues. To validate the importance of sidechains in supramolecular architectural stabilization, herein this report describes the self-assembly propensities involving weak interactions in a series of model tripeptides Boc-Xaa-Aib-Yaa-OMe I-IV, (where Xaa = 4-F-Phe/NMeSer/Ile & Yaa = Tyr in peptide I-III respectively and Xaa = 4-F-Phe & Yaa = Ile in peptide IV) differing in terminal side chains. The solid state structural analysis reveals that tripeptide (I) displays supramolecular preference for double helical architecture. However, when slight modification has been introduced in the N-terminal side chains disfavour the double helical organisation (Peptide II and III). Indeed the peptides display sheet like ensemble within the framework. Besides replacement of C-terminal Tyr by Ile in peptide I even do not promote the architecture, emphasizing the dominant role of balance of side chains in stabilizing double helical organisation. The CD measurements, concentration dependant studies, NMR titrations and ROESY spectra are well in agreement with the solid state conformational investigation. Moreover the morphological experiments utilizing FE-SEM, support the heterogeneity present in the peptides. Thus this work may not only hold future promise in understanding the structure and function of neurodegenerative diseases but also assist in rational design of protein modification in biologically active peptides.

Folding of polyglutamine chains

NASA Astrophysics Data System (ADS)

Chopra, Manan; Reddy, Allam S.; Abbott, N. L.; de Pablo, J. J.

2008-10-01

Long polyglutamine chains have been associated with a number of neurodegenerative diseases. These include Huntington's disease, where expanded polyglutamine (PolyQ) sequences longer than 36 residues are correlated with the onset of symptoms. In this paper we study the folding pathway of a 54-residue PolyQ chain into a β-helical structure. Transition path sampling Monte Carlo simulations are used to generate unbiased reactive pathways between unfolded configurations and the folded β-helical structure of the polyglutamine chain. The folding process is examined in both explicit water and an implicit solvent. Both models reveal that the formation of a few critical contacts is necessary and sufficient for the molecule to fold. Once the primary contacts are formed, the fate of the protein is sealed and it is largely committed to fold. We find that, consistent with emerging hypotheses about PolyQ aggregation, a stable β-helical structure could serve as the nucleus for subsequent polymerization of amyloid fibrils. Our results indicate that PolyQ sequences shorter than 36 residues cannot form that nucleus, and it is also shown that specific mutations inferred from an analysis of the simulated folding pathway exacerbate its stability.

Structural propensities and entropy effects in peptide helix-coil transitions

NASA Astrophysics Data System (ADS)

Chemmama, Ilan E.; Pelea, Adam Colt; Bhandari, Yuba R.; Chapagain, Prem P.; Gerstman, Bernard S.

2012-09-01

The helix-coil transition in peptides is a critical structural transition leading to functioning proteins. Peptide chains have a large number of possible configurations that must be accounted for in statistical mechanical investigations. Using hydrogen bond and local helix propensity interaction terms, we develop a method for obtaining and incorporating the degeneracy factor that allows the exact calculation of the partition function for a peptide as a function of chain length. The partition function is used in calculations for engineered peptide chains of various lengths that allow comparison with a variety of different types of experimentally measured quantities, such as fraction of helicity as a function of both temperature and chain length, heat capacity, and denaturation studies. When experimental sensitivity in helicity measurements is properly accounted for in the calculations, the calculated curves fit well with the experimental curves. We determine values of interaction energies for comparison with known biochemical interactions, as well as quantify the difference in the number of configurations available to an amino acid in a random coil configuration compared to a helical configuration.

P3h3-null and Sc65-null Mice Phenocopy the Collagen Lysine Under-hydroxylation and Cross-linking Abnormality of Ehlers-Danlos Syndrome Type VIA.

PubMed

Hudson, David M; Weis, MaryAnn; Rai, Jyoti; Joeng, Kyu Sang; Dimori, Milena; Lee, Brendan H; Morello, Roy; Eyre, David R

2017-03-03

Tandem mass spectrometry was applied to tissues from targeted mutant mouse models to explore the collagen substrate specificities of individual members of the prolyl 3-hydroxylase (P3H) gene family. Previous studies revealed that P3h1 preferentially 3-hydroxylates proline at a single site in collagen type I chains, whereas P3h2 is responsible for 3-hydroxylating multiple proline sites in collagen types I, II, IV, and V. In screening for collagen substrate sites for the remaining members of the vertebrate P3H family, P3h3 and Sc65 knock-out mice revealed a common lysine under-hydroxylation effect at helical domain cross-linking sites in skin, bone, tendon, aorta, and cornea. No effect on prolyl 3-hydroxylation was evident on screening the spectrum of known 3-hydroxyproline sites from all major tissue collagen types. However, collagen type I extracted from both Sc65 -/- and P3h3 -/- skin revealed the same abnormal chain pattern on SDS-PAGE with an overabundance of a γ 112 cross-linked trimer. The latter proved to be from native molecules that had intramolecular aldol cross-links at each end. The lysine under-hydroxylation was shown to alter the divalent aldimine cross-link chemistry of mutant skin collagen. Furthermore, the ratio of mature HP/LP cross-links in bone of both P3h3 -/- and Sc65 -/- mice was reversed compared with wild type, consistent with the level of lysine under-hydroxylation seen in individual chains at cross-linking sites. The effect on cross-linking lysines was quantitatively very similar to that previously observed in EDS VIA human and Plod1 -/- mouse tissues, suggesting that P3H3 and/or SC65 mutations may cause as yet undefined EDS variants. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Precise structural analysis of α-helical polypeptide by quantum-chemical calculation related to reciprocal side-chain combination of two L-phenylalanine residues

NASA Astrophysics Data System (ADS)

Niimura, Subaru; Kurosu, Hiromichi; Shoji, Akira

2010-04-01

To clarify the positive role of side-chain conformation in the stability of protein secondary structure (main-chain conformation), we successfully calculated the optimization structure of a series of well-defined α-helical octadecapeptides composed of two L-phenylalanine (Phe) and 16 L-alanine (Ala) residues, based on the molecular orbital calculation with density functional theory (DFT/B3LYP/6-31G(d)). From the total energy calculation and the precise secondary structural analysis, we found that the conformational stability of the α-helix is closely related to the reciprocal side-chain combinations (such as positional relation and side-chain conformation) of two Phe residues in this system. Furthermore, we demonstrated that the 1H, 13C, 15N and 17O isotropic chemical shifts of each Phe residue depend on the respective side-chain conformations of the Phe residue.

Collagen cross-linking: insights on the evolution of metazoan extracellular matrix.

PubMed

Rodriguez-Pascual, Fernando; Slatter, David Anthony

2016-11-23

Collagens constitute a large family of extracellular matrix (ECM) proteins that play a fundamental role in supporting the structure of various tissues in multicellular animals. The mechanical strength of fibrillar collagens is highly dependent on the formation of covalent cross-links between individual fibrils, a process initiated by the enzymatic action of members of the lysyl oxidase (LOX) family. Fibrillar collagens are present in a wide variety of animals, therefore often being associated with metazoan evolution, where the emergence of an ancestral collagen chain has been proposed to lead to the formation of different clades. While LOX-generated collagen cross-linking metabolites have been detected in different metazoan families, there is limited information about when and how collagen acquired this particular modification. By analyzing telopeptide and helical sequences, we identified highly conserved, potential cross-linking sites throughout the metazoan tree of life. Based on this analysis, we propose that they have importantly contributed to the formation and further expansion of fibrillar collagens.

Zn(II) coordination polymers with flexible V-shaped dicarboxylate ligand: Syntheses, helical structures and properties

NASA Astrophysics Data System (ADS)

Li, Lin; Liu, Chong-Bo; Yang, Gao-Shan; Xiong, Zhi-Qiang; Liu, Hong; Wen, Hui-Liang

2015-11-01

Hydrothermal reactions of 2,2‧-[hexafluoroisopropylidenebis(p-phenyleneoxy)]diacetic acid (H2L) and zinc ions in the presence of N-donor ancillary ligands afford four novel coordination polymers, namely, [Zn2(μ2-OH)(μ4-O)0.5(L)]·0.5H2O (1), [Zn(L)(2,2‧-bipy)(H2O)] (2), [Zn3(L)3(phen)2]·H2O (3) and [Zn2(L)2(4,4‧-bipy)] (4) (2,2‧-bipy=2,2‧-bipyridine; 4,4‧-bipy=4,4‧-bipyridine; phen=1,10-phenanthroline). Their structures have been determined by single-crystal X-ray diffraction analyses, elemental analyses, IR spectra, powder X-ray diffraction (PXRD), and thermogravimetric (TG) analyses. Complex 1 shows a 3-D clover framework consisting of [Zn4(μ4-O)(μ2-OH)2]4+ clusters, and exhibits a novel (3,8)-connected topological net with the Schläfli symbol of {3·4·5}2{34·44·52·66·710·82}, and contains double-stranded and two kinds of meso-helices. 2 displays a helical chain structure, which is further extended via hydrogen bonds into a 3-D supramolecular structure with meso-helix chains. 3 displays a 2-D {44·62} parallelogram structure, which is further extended via hydrogen bonds into a 3-D supramolecular structure with single-stranded helical chains. 4 shows a 2-D {44·62} square structure with left- and right-handed helical chains. Moreover, the luminescent properties of 1-4 have been investigated.

High-resolution protein design with backbone freedom.

PubMed

Harbury, P B; Plecs, J J; Tidor, B; Alber, T; Kim, P S

1998-11-20

Recent advances in computational techniques have allowed the design of precise side-chain packing in proteins with predetermined, naturally occurring backbone structures. Because these methods do not model protein main-chain flexibility, they lack the breadth to explore novel backbone conformations. Here the de novo design of a family of alpha-helical bundle proteins with a right-handed superhelical twist is described. In the design, the overall protein fold was specified by hydrophobic-polar residue patterning, whereas the bundle oligomerization state, detailed main-chain conformation, and interior side-chain rotamers were engineered by computational enumerations of packing in alternate backbone structures. Main-chain flexibility was incorporated through an algebraic parameterization of the backbone. The designed peptides form alpha-helical dimers, trimers, and tetramers in accord with the design goals. The crystal structure of the tetramer matches the designed structure in atomic detail.

Seven 3d-4f coordination polymers of macrocyclic oxamide with polycarboxylates: Syntheses, crystal structures and magnetic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xin, Na; Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, Ministry of Education; Tianjin Key Laboratory of Structure and Performance for Functional Molecules

2016-11-15

Seven new 3d–4f heterometallic coordination polymers, [Ln(CuL){sub 2}(Hbtca)(btca)(H{sub 2}O)]·2H{sub 2}O (Ln = Tb{sup III}1, Pr{sup III}2, Sm{sup III}3, Eu{sup III}4, Yb{sup III}5), [Nd(NiL)(nip)(Rnip)]·0·25H{sub 2}O·0.25CH{sub 3}OH (R= 0.6CH{sub 3}, 0.4H) 6 and [Nd{sub 2}(NiL)(nip){sub 3}(H{sub 2}O)]·2H{sub 2}O 7(CuL or NiL, H{sub 2}L = 2, 3-dioxo-5, 6, 14, 15-dibenzo-1, 4, 8, 12-tetraazacyclo-pentadeca-7, 13-dien; H{sub 2}btca = benzotriazole-5-carboxylic acid; H{sub 2}nip = 5-nitroisophthalic acid) have been synthesized by a solvothermal method and characterized by single-crystal X-ray diffraction. Complexes 1–5 exhibit a double-strand meso-helical chain structures formed by [Ln{sup III}Cu{sup II}{sub 2}] units via the oxamide and benzotriazole-5-carboxylate bridges, while complex 6 exhibits amore » four-strand meso-helical chain formed by NdNi unit via the oxamide and 5-nitroisophthalate bridges. Complex 7 consists of a 2D layer framework formed by four-strand meso-helical chain via the nip{sup 2−} bridges. Moreover, the magnetic properties of them were investigated, and the best-fit analysis of χ{sub M}T versus T show that the anisotropic contribution of Ln(III) ions (arising from the spin-orbit coupling or the crystal field perturbation) dominates (weak exchange limit) in these complexes(for 3, λ = 214.6 cm{sup −1}, zj’ = −0.33 cm{sup −1}, g{sub av} = 1.94; for 5, Δ = 6.98 cm{sup −1}, zj’ = 1.53 cm{sup −1}, g{sub av} = 1.85). - Graphical-abstract: Seven novel oxamido-bridged 3d-4f heterometallic coordination polymers with benzotriazole-5-carboxylate or 5-nitroisophthalate co-ligands under solvothermal reaction conditions. Polymers 1–7 hold 1D or 2D framework structure, viz., double-strand meso-helical chain of 1–5, four-strand meso-helical chain of 6, and 2D net of 7 consisting of four-strand meso-helical chain. Moreover, the temperature dependences of magnetic susceptibilities of compounds 1–7 were also studied.« less

GammaM23K, gammaM232K, and gammaL77K single substitutions in the TF1-ATPase lower ATPase activity by disrupting a cluster of hydrophobic side chains.

PubMed

Bandyopadhyay, Sanjay; Allison, William S

2004-07-27

In crystal structures of the bovine F(1)-ATPase (MF(1)), the side chains of gammaMet(23), gammaMet(232), and gammaLeu(77) interact in a cluster. Substitution of the corresponding residues in the alpha(3)beta(3)gamma subcomplex of TF(1) with lysine lowers the ATPase activity to 2.3, 11, and 15%, respectively, of that displayed by wild-type. In contrast, TF(1) subcomplexes containing the gammaM(23)C, gammaM(232)C, and gammaL(77)C substitutions display 36, 36, and 130%, respectively, of the wild-type ATPase activity. The ATPase activity of the gammaM(23)C/gammaM(232)C double mutant subcomplex is 36% that of the wild-type subcomplex before and after cross-linking the introduced cysteines, whereas the ATPase activity of the gammaM(23)C/L(77)C double mutant increased from 50 to 85% that of wild-type after cross-linking the introduced cysteines. Only beta-beta cross-links formed when the alpha(3)(betaE(395)C)(3)gammaM(23)C double mutant was inactivated with CuCl(2). The overall results suggest that the attenuated ATPase of the mutant subcomplexes containing the gammaM(23)K, gammaL(77)K, and gammaM(232)K substitutions is caused by disruption of the cluster of hydrophobic amino acid side chains and that the midregion of the coiled-coil comprised of the amino- and carboxyl-terminal alpha helices of the gamma subunit does not undergo unwinding or major displacement from the side chain of gammaLeu(77) during ATP-driven rotation of the gamma subunit.

Zn(II) coordination polymers with flexible V-shaped dicarboxylate ligand: Syntheses, helical structures and properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Lin; Liu, Chong-Bo, E-mail: cbliu@nchu.edu.cn; Yang, Gao-Shan

2015-11-15

Hydrothermal reactions of 2,2′-[hexafluoroisopropylidenebis(p-phenyleneoxy)]diacetic acid (H{sub 2}L) and zinc ions in the presence of N-donor ancillary ligands afford four novel coordination polymers, namely, [Zn{sub 2}(μ{sub 2}-OH)(μ{sub 4}-O){sub 0.5}(L)]·0.5H{sub 2}O (1), [Zn(L)(2,2′-bipy)(H{sub 2}O)] (2), [Zn{sub 3}(L){sub 3}(phen){sub 2}]·H{sub 2}O (3) and [Zn{sub 2}(L){sub 2}(4,4′-bipy)] (4) (2,2′-bipy=2,2′-bipyridine; 4,4′-bipy=4,4′-bipyridine; phen=1,10-phenanthroline). Their structures have been determined by single-crystal X-ray diffraction analyses, elemental analyses, IR spectra, powder X-ray diffraction (PXRD), and thermogravimetric (TG) analyses. Complex 1 shows a 3-D clover framework consisting of [Zn{sub 4}(µ{sub 4}-O)(µ{sub 2}-OH){sub 2}]{sup 4+} clusters, and exhibits a novel (3,8)-connected topological net with the Schläfli symbol of {3·4·5}{sub 2}{3"4·4"4·5"2·6"6·7"1"0·8"2}, andmore » contains double-stranded and two kinds of meso-helices. 2 displays a helical chain structure, which is further extended via hydrogen bonds into a 3-D supramolecular structure with meso-helix chains. 3 displays a 2-D {4"4·6"2} parallelogram structure, which is further extended via hydrogen bonds into a 3-D supramolecular structure with single-stranded helical chains. 4 shows a 2-D {4"4·6"2} square structure with left- and right-handed helical chains. Moreover, the luminescent properties of 1–4 have been investigated. - Graphical abstract: Four new Zn(II) coordination polymers with helical structures based on flexible V-shaped dicarboxylate ligand have been synthesized and structurally characterized. Photoluminescent properties have been investigated. - Highlights: • Four novel Zn(II) coordination polymers with V-shaped ligand were characterized. • Complexes 1–4 show diverse intriguing helical characters. • Fluorescence properties of complexes 1–4 were investigated.« less

Structure of a short-chain dehydrogenase/reductase from Bacillus anthracis

PubMed Central

Hou, Jing; Wojciechowska, Kamila; Zheng, Heping; Chruszcz, Maksymilian; Cooper, David R.; Cymborowski, Marcin; Skarina, Tatiana; Gordon, Elena; Luo, Haibin; Savchenko, Alexei; Minor, Wladek

2012-01-01

The crystal structure of a short-chain dehydrogenase/reductase from Bacillus anthracis strain ‘Ames Ancestor’ complexed with NADP has been determined and refined to 1.87 Å resolution. The structure of the enzyme consists of a Rossmann fold composed of seven parallel β-strands sandwiched by three α-­helices on each side. An NADP molecule from an endogenous source is bound in the conserved binding pocket in the syn conformation. The loop region responsible for binding another substrate forms two perpendicular short helices connected by a sharp turn. PMID:22684058

Passive micromixers with dual helical channels

NASA Astrophysics Data System (ADS)

Liu, Keyin; Yang, Qing; Chen, Feng; Zhao, Yulong; Meng, Xiangwei; Shan, Chao; Li, Yanyang

2015-02-01

In this study, a three-dimensional (3D) micromixer with cross-linked double helical microchannels is studied to achieve rapid mixing of fluids at low Reynolds numbers (Re). The 3D micromixer takes full advantages of the chaotic advection model with helical microchannels; meanwhile, the proposed crossing structure of double helical microchannels enables two flow patterns of repelling flow and straight flow in the fluids to promote the agitation effect. The complex 3D micromixer is realized by an improved femtosecond laser wet etching (FLWE) technology embedded in fused silica. The mixing results show that cross-linked double helical microchannels can achieve excellent mixing within 3 cycles (300 μm) over a wide range of low Re (1.5×10-3~600), which compare well with the conventional passive micromixers. This highly-effective micromixer is hoped to contribute to the integration of microfluidic systems.

Empirical parameterization of a model for predicting peptide helix/coil equilibrium populations.

PubMed Central

Andersen, N. H.; Tong, H.

1997-01-01

A modification of the Lifson-Roig formulation of helix/coil transitions is presented; it (1) incorporates end-capping and coulombic (salt bridges, hydrogen bonding, and side-chain interactions with charged termini and the helix dipole) effects, (2) helix-stabilizing hydrophobic clustering, (3) allows for different inherent termination probabilities of individual residues, and (4) differentiates helix elongation in the first versus subsequent turns of a helix. Each residue is characterized by six parameters governing helix formation. The formulation of the conditional probability of helix initiation and termination that we developed is essentially the same as one presented previously (Shalongo W, Stellwagen, E. 1995. Protein Sci 4:1161-1166) and nearly the mathematical equivalent of the new capping formulation incorporated in the model presented by Rohl et al. (1996. Protein Sci 5:2623-2637). Side-chain/side-chain interactions are, in most cases, incorporated as context dependent modifications of propagation rather than nucleation parameters. An alternative procedure for converting [theta]221 values to experimental fractional helicities () is presented. Tests of the program predictions suggest this method may have some advantages both for designed peptides and for the analysis of secondary structure preferences that could drive the formation of molten-globule intermediates on protein folding pathways. The model predicts the fractional helicity of 385 peptides with a root-mean-square deviation (RMSD) of 0.050 and locates (with precise definition of the termini in many cases) helices in proteins as well as competing methods. The propagation and nucleation parameters were derived from NMR data and from the CD data for a 79 peptide "learning set" for which an excellent fit resulted (RMSD = 0.0295). The current set of parameter corrections for capping boxes, helix dipole interactions, and side-chain/side-chain interactions (coulombic, hydrogen bonding and hydrophobic clustering), although still under development provide a significant improvement in both helix/coil equilibrium prediction for peptides and helix location in protein sequences. This is clearly evident in the rms deviations between CD measures and calculated values of fractional helicity for different classes of peptides before and after applying the corrections: for peptides lacking capping boxes and i/i + 3 and i/i + 4 side-chain/side-chain interactions RMSD = 0.044 (n = 164) versus RMSD = 0.054 (0.172 without the corrections, n = 221) for peptides that required context-dependent corrections of the parameters. If we restrict the analysis to N-acylated peptides with helix stabilizing side-chain/side-chain interactions (including N-capping boxes), the degree to which our corrections account for the stabilizing interaction can be judged from the change in helicity underestimation, (calc-CD): -0.15 +/- 0.10, which is reduced to -0.018 +/- 0.048 (n = 191) upon applying the corrections. PMID:9300492

The Contribution of Interchain Salt Bridges to Triple-Helical Stability in Collagen

PubMed Central

Gurry, Thomas; Nerenberg, Paul S.; Stultz, Collin M.

2010-01-01

Abstract Studies on collagen and collagen-like peptides suggest that triple-helical stability can vary along the amino acid chain. In this regard, it has been shown that lysine residues in the Y position and acidic residues in the X′ position of (GPO)3GXYGX′Y′(GPO)3 peptides lead to triple-helical structures with melting temperatures similar to (GPO)8 (where O is hydroxyproline), which is generally regarded as the most stable collagen-like sequence of this length. This enhanced stability has been attributed to the formation of salt bridges between adjacent collagen chains. In this study, we explore the relationship between interchain salt bridge formation and triple-helical stability using detailed molecular simulations. Although our results confirm that salt bridges promote triple-helical stability, we find that not all salt bridges are created equal. In particular, lysine-glutamate salt bridges are most stabilizing when formed between residues in the middle strand (B) and the trailing strand (C), whereas lysine-aspartate salt bridges are most stabilizing when formed between residues in the leading (A) and middle (B) strand—the latter observation being consistent with recent NMR data on a heterotrimeric model peptide. Overall, we believe these data clarify the role of salt bridges in modulating triple-helical stability and can be used to guide the design of collagen-like peptides that have specific interchain interactions. PMID:20513408

Computational study of the fibril organization of polyglutamine repeats reveals a common motif identified in beta-helices.

PubMed

Zanuy, David; Gunasekaran, Kannan; Lesk, Arthur M; Nussinov, Ruth

2006-04-21

The formation of fibril aggregates by long polyglutamine sequences is assumed to play a major role in neurodegenerative diseases such as Huntington. Here, we model peptides rich in glutamine, through a series of molecular dynamics simulations. Starting from a rigid nanotube-like conformation, we have obtained a new conformational template that shares structural features of a tubular helix and of a beta-helix conformational organization. Our new model can be described as a super-helical arrangement of flat beta-sheet segments linked by planar turns or bends. Interestingly, our comprehensive analysis of the Protein Data Bank reveals that this is a common motif in beta-helices (termed beta-bend), although it has not been identified so far. The motif is based on the alternation of beta-sheet and helical conformation as the protein sequence is followed from the N to the C termini (beta-alpha(R)-beta-polyPro-beta). We further identify this motif in the ssNMR structure of the protofibril of the amyloidogenic peptide Abeta(1-40). The recurrence of the beta-bend suggests a general mode of connecting long parallel beta-sheet segments that would allow the growth of partially ordered fibril structures. The design allows the peptide backbone to change direction with a minimal loss of main chain hydrogen bonds. The identification of a coherent organization beyond that of the beta-sheet segments in different folds rich in parallel beta-sheets suggests a higher degree of ordered structure in protein fibrils, in agreement with their low solubility and dense molecular packing.

Increasing molecular weight parameters of a helical polymer through polymerization in a chiral solvent.

PubMed

Holder, Simon J; Achilleos, Mariliz; Jones, Richard G

2006-09-27

In this communication, we will demonstrate that polymerization in a chiral solvent can affect the molecular weight distribution of the product by perturbing the balance of the P and M helical screw senses of the growing chains. Specifically, for the Wurtz-type synthesis of polymethylphenylsilane (PMPS) in either (R) or (S)-limonene, the weight-average molecular weight of the products (average Mw = 80 000) was twice that of PMPS synthesized in (R/S)-limonene (average Mw = 39 200). Peturbation of the helical segmentation along the polymer chains leads to a reduction in the rate of occurrence of a key termination step. This the first time that a chiral solvent has been demonstrated to have such an effect on a polymerization process in affecting molecular weight parameters in contrast to affecting tacticity.

A novel representation of the conformational structure of transfer RNAs. Correlation of the folding patterns of the polynucleotide chain with the base sequence and the nucleotide backbone torsions.

PubMed Central

Srinivasan, A R; Yathindra, N

1977-01-01

A novel description of the conformational characteristics of all the individual nucleotides and the phosphodiesters in tRNAs is presented in the form of a circular plot. This representation furnishes information of the base sequence with the folding patterns of the polynucleotide chain as one traverses along the circumference and with the individual nucleotide and phosphodiester linkage torsions along the radii. The circular plot obtained for yeast tRNAPhe strikingly distinguishes the helical and the loop regions. The variation of the different nucleotide torsions along the entire chain length and their effect on the secondary helical and tertiary loop regions become readily apparent. PMID:339206

The phosphorylation site in double helical amylopectin as investigated by a combined approach using chemical synthesis, crystallography and molecular modeling.

PubMed

Engelsen, Søren Balling; Madsen, Anders Østergaard; Blennow, Andreas; Motawia, Mohammed Saddik; Møller, Birger Lindberg; Larsen, Sine

2003-04-24

The only known in planta substitution of starch is phosphorylation. Whereas the function of starch phosphorylation is poorly understood, phosphorylated starch possesses improved functionality in vitro. Molecular models of native crystalline starch are currently being developed and the starch phosphorylating enzyme has recently been discovered. Accordingly, it is desirable to obtain a more exact description of the molecular structures of phosphorylated starch. We have determined the crystal structure of methyl alpha-D-glucopyranoside 6-O-phosphate as its potassium salt which is thought to be the starch phosphate counterion in vivo. From this structure and previously known glucophosphate structures we describe the possible 6-O-phosphate geometries and through modeling extrapolate the results to the double helical structure of the crystalline part of amylopectin. The geometries of the existing crystal structures of 6-O-phosphate groups were found to belong to two main adiabatic valleys. One of these conformations could be fitted into the double helical amylopectin part without perturbing the double helical amylopectin structure and without creating steric problems for the hexagonal chain-chain packing.

Competition between B-Z and B-L transitions in a single DNA molecule: Computational studies

NASA Astrophysics Data System (ADS)

Kwon, Ah-Young; Nam, Gi-Moon; Johner, Albert; Kim, Seyong; Hong, Seok-Cheol; Lee, Nam-Kyung

2016-02-01

Under negative torsion, DNA adopts left-handed helical forms, such as Z-DNA and L-DNA. Using the random copolymer model developed for a wormlike chain, we represent a single DNA molecule with structural heterogeneity as a helical chain consisting of monomers which can be characterized by different helical senses and pitches. By Monte Carlo simulation, where we take into account bending and twist fluctuations explicitly, we study sequence dependence of B-Z transitions under torsional stress and tension focusing on the interaction with B-L transitions. We consider core sequences, (GC) n repeats or (TG) n repeats, which can interconvert between the right-handed B form and the left-handed Z form, imbedded in a random sequence, which can convert to left-handed L form with different (tension dependent) helical pitch. We show that Z-DNA formation from the (GC) n sequence is always supported by unwinding torsional stress but Z-DNA formation from the (TG) n sequence, which are more costly to convert but numerous, can be strongly influenced by the quenched disorder in the surrounding random sequence.

Alternating phenylene and furan/pyrrole/thiophene units-based oligomers: A computational study of the structures and optoelectronic properties

NASA Astrophysics Data System (ADS)

Sahu, Harikrishna; Shukla, Rishabh; Goswami, Juri; Gaur, Priyank; Panda, Aditya N.

2018-01-01

Structural and optoelectronic properties of phenylene-furan, phenylene-pyrrole and phenylene-thiophene oligomers are reported using density functional theory methods. Studies reveal that stabilities of conformers change with increasing chain length, and helical conformers are energetically feasible for large oligomers of the studied systems, due to stacking interactions between adjacent helical turns. Absorption spectra of helices are dominated by multiple number of electronic transitions other than the S0 →S1 , involving orbitals other than the HOMO/LUMO. All studied helices are optically active having similar pattern of negative and positive peaks in the CD spectra.

Free-fall dynamics of a pair of rigidly linked disks

NASA Astrophysics Data System (ADS)

Kim, Taehyun; Chang, Jaehyeock; Kim, Daegyoum

2018-03-01

We investigate experimentally the free-fall motion of a pair of identical disks rigidly connected to each other. The three-dimensional coordinates of the pair of falling disks were constructed to quantitatively describe its trajectory, and the flow structure formed by the disk pair was identified by using dye visualization. The rigidly linked disk pair exhibits a novel falling pattern that creates a helical path with a conical configuration in which the lower disk rotates in a wider radius than the upper disk with respect to a vertical axis. The helical motion occurs consistently for the range of disk separation examined in this study. The dye visualization reveals that a strong, noticeable helical vortex core is generated from the outer tip of the lower disk during the helical motion. With an increasing length ratio, which is the ratio of the disk separation to the diameter of the disks, the nutation angle and the rate of change in the precession angle that characterize the combined helical and conical kinematics decrease linearly, whereas the pitch of the helical path increases linearly. Although all disk pairs undergo this helical motion, the horizontal-drift patterns of the disk pair depend on the length ratio.

Crystal structure of 3-amino-1-(4-meth-oxy-phen-yl)-1H-benzo[f]chromene-2-carbo-nitrile.

PubMed

Mohamed, Shaaban K; Horton, Peter N; Akkurt, Mehmet; Younes, Sabry H H; Albayati, Mustafa R

2015-07-01

In the title compound, C21H16N2O2, the meth-oxy-benzene ring is almost perpendicular to the mean plane of the naphthalene ring system, making a dihedral angle of 83.62 (5)°. The 4H-pyran ring fused with the naphthalene ring system is almost planar [maximum deviation = 0.033 (1) Å]. In the crystal, mol-ecules are linked into inversion dimers by pairs of N-H⋯N hydrogen bonds. N-H⋯O hydrogen bonds connect the dimers, forming a helical supra-molecular chain along the a-axis direction. The crystal packing also features C-H⋯π inter-actions.

Micro-Hall magnetometry on a Co-organic chain compound

NASA Astrophysics Data System (ADS)

Rolland, L.; Simonet, V.; Wernsdorfer, W.; Bogani, L.; Sessoli, R.

2004-05-01

The static and dynamical properties of Co-organic chains, with strong magnetic anisotropy, are studied by micro-Hall magnetometry. The low-temperature hysteresis cycles are discussed with respect to the helical structure of the chains. Thermally activated relaxation of the magnetization is observed, compatible with the Glauber model for a 1D Ising system.

Adsorption and Conformation Change of Helical Peptides on Colloidal Silica

NASA Astrophysics Data System (ADS)

Read, Michael; Zhang, Shuguang; Mayes, Anne; Burkett, Sandra

2001-03-01

Helical conformations of short peptides in solution are partly stabilized by the pattern of electrostatic charge formed by the amino acid sequence. We have studied the role of electrostatics in the adsorption and helix-coil transition of peptides on oxide surfaces. Adsorption isotherms, along with a combination of spectroscopic techniques, show that this is a reversible equilibrium process. Strong electrostatic forces between ionic side chains and charged surface sites increase the adsorbed amount, and promote a loss of helicity in the adsorbed state qualitatively different from that observed upon thermal or chemical perturbation. The electrical dipole of the peptide, arising from the amino acid side chains, serves to orient the molecules on the surface. Effects of adsorption, orientation, and conformation change on the activity of peptides in model biological reactions, as well as the relevance of this simplified system to protein adsorption, are considered.

Exploring the kinetics of gelation and final architecture of enzymatically cross-linked chitosan/gelatin gels.

PubMed

da Silva, Marcelo A; Bode, Franziska; Grillo, Isabelle; Dreiss, Cécile A

2015-04-13

Small-angle neutron scattering (SANS) was used to characterize the nanoscale structure of enzymatically cross-linked chitosan/gelatin hydrogels obtained from two protocols: a pure chemical cross-linking process (C), which uses the natural enzyme microbial transglutaminase, and a physical-co-chemical (PC) hybrid process, where covalent cross-linking is combined with the temperature-triggered gelation of gelatin, occurring through the formation of triple-helices. SANS measurements on the final and evolving networks provide a correlation length (ξ), which reflects the average size of expanding clusters. Their growth in PC gels is restricted by the triple-helices (ξ ∼ 10s of Å), while ξ in pure chemical gels increases with cross-linker concentration (∼100s of Å). In addition, the shear elastic modulus in PC gels is higher than in pure C gels. Our results thus demonstrate that gelatin triple helices provide a template to guide the cross-linking process; overall, this work provides important structural insight to improve the design of biopolymer-based gels.

Breathers and rogue waves in a Heisenberg ferromagnetic spin chain or an alpha helical protein

NASA Astrophysics Data System (ADS)

Yang, Jin-Wei; Gao, Yi-Tian; Su, Chuan-Qi; Wang, Qi-Min; Lan, Zhong-Zhou

2017-07-01

In this paper, a fourth-order variable-coefficient nonlinear Schrödinger equation for a one-dimensional continuum anisotropic Heisenberg ferromagnetic spin chain or an alpha helical protein has been investigated. Breathers and rogue waves are constructed via the Darboux transformation and generalized Darboux transformation, respectively. Results of the breathers and rogue waves are presented: (1) The first- and second-order Akhmediev breathers and Kuznetsov-Ma solitons are presented with different values of variable coefficients which are related to the energy transfer or higher-order excitations and interactions in the helical protein, or related to the spin excitations resulting from the lowest order continuum approximation and octupole-dipole interaction in a Heisenberg ferromagnetic spin chain, and the nonlinear periodic breathers resulting from the Akhmediev breathers are studied as well; (2) For the first- and second-order rogue waves, we find that they can be split into many similar components when the variable coefficients are polynomial functions of time; (3) Rogue waves can also be split when the variable coefficients are hyperbolic secant functions of time, but the profile of each component in such a case is different.

Chiral monolithic absorbent constructed by optically active helical-substituted polyacetylene and graphene oxide: preparation and chiral absorption capacity.

PubMed

Li, Weifei; Wang, Bo; Yang, Wantai; Deng, Jianping

2015-02-01

Chiral monolithic absorbent is successfully constructed for the first time by using optically active helical-substituted polyacetylene and graphene oxide (GO). The preparative strategy is facile and straightforward, in which chiral-substituted acetylene monomer (Ma), cross-linker (Mb), and alkynylated GO (Mc) undergo copolymerization to form the desired monolithic absorbent in quantitative yield. The resulting monoliths are characterized by circular dichroism, UV-vis absorption, scanning electron microscopy (SEM), FT-IR, Raman, energy-dispersive spectrometer (EDS), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), XPS, and thermogravimetric analysis (TGA) techniques. The polymer chains derived from Ma form chiral helical structures and thus provide optical activity to the monoliths, while GO sheets contribute to the formation of porous structures. The porous structure enables the monolithic absorbents to demonstrate a large swelling ratio in organic solvents, and more remarkably, the helical polymer chains provide optical activity and further enantio-differentiating absorption ability. The present study establishes an efficient and versatile methodology for preparing novel functional materials, in particular monolithic chiral materials based on substituted polyacetylene and GO. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Crystallization and Microphase Separation in Chiral Block Copolymers

NASA Astrophysics Data System (ADS)

Ho, Rong-Ming

2012-02-01

Block copolymers composed of chiral entities, denoted as chiral block copolymers (BCP*s), were designed to fabricate helical architectures from self-assembly. A helical phase (denoted H*) was discovered in the self-assembly of poly(styrene)-b-poly(L-lactide) (PS-PLLA) BCPs*. To examine the phase behavior of the PS-PLLA, self-assembled superstructures resulting from the competition between crystallization and microphase separation of the PS-PLLA in solution were examined. A kinetically controlled process by changing non-solvent addition rate was utilized to control the BCP* self-assembly. Single-crystal lozenge lamellae were obtained by the slow self-assembly (i.e., slow non-solvent addition rate) of PS-PLLA whereas amorphous helical ribbon superstructures were obtained from the fast self-assembly (i.e., fast non-solvent addition rate). As a result, the formation of helical architectures from the self-assembly of the PS-PLLA reflects the impact of chirality on microphase separation, but the chiral effect might be overwhelmed by crystallization. Consequently, various crystalline PS-PLLA nanostructures in bulk were obtained by controlling the crystallization temperature of PLLA (Tc,PLLA) at which crystalline helices and crystalline cylinders occur while Tc,PLLA=x Tg,PS, respectively. Anisotropic arrangement of the PLLA crystallites grown within the microdomains was identified. The formation of this exclusive crystalline growth is attributed to the spatial confinement effect for crystallization. While Tc,PLLA=x Tg,PS, the preferential growth may modulate the curvature of microdomains by shifting the molecular chains to access the fast path for crystalline growth due to the increase in chain mobility. As a result, a spring-like behavior of the helical nanostructure can be driven by crystallization so as to dictate the transformation of helices and to result in crystalline cylinders.

X-linked Alport syndrome: An SSCP-based mutation survey over all 51 exons of the COL4A5 gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renieri, A.; Bruttini, M.; Galli, L.

1996-06-01

The COL4A5 gene encodes the {alpha}5 (type IV) collagen chain and is defective in X-linked Alport syndrome (AS). Here, we report the first systematic analysis of all 51 exons of COL4A5 gene in a series of 201 Italian AS patients. We have previously reported nine major rearrangements, as well as 18 small mutations identified in the same patient series by SSCP analysis of several exons. After systematic analysis of all 51 exons of COL4A5, we have now identified 30 different mutations: 10 glycine substitutions in the triple helical domain of the protein, 9 frameshift mutations, 4 in-frame deletions, 1 startmore » codon, 1 nonsense, and 5 splice-site mutations. These mutations were either unique or found in two unrelated families, thus excluding the presence of a common mutation in the coding part of the gene. Overall, mutations were detected in only 45% of individuals with a certain or likely diagnosis of X-linked AS. This finding suggests that mutations in noncoding segments of COL4A5 account for a high number of X-linked AS cases. An alternative hypothesis is the presence of locus heterogeneity, even within the X-linked form of the disease. A genotype/phenotype comparison enabled us to better substantiate a significant correlation between the degree of predicted disruption of the {alpha}5 chain and the severity of phenotype in affected male individuals. Our study has significant implications in the diagnosis and follow-up of AS patients. 44 refs., 3 figs., 4 tabs.« less

An Experimentally Robust Model of Monomeric Apolipoprotein A-I Created from a Chimera of Two X-ray Structures and Molecular Dynamics Simulations

PubMed Central

2015-01-01

High-density lipoprotein (HDL) retards atherosclerosis by accepting cholesterol from the artery wall. However, the structure of the proposed acceptor, monomeric apolipoprotein A-I (apoA-I), the major protein of HDL, is poorly understood. Two published models for monomeric apoA-I used cross-linking distance constraints to derive best fit conformations. This approach has limitations. (i) Cross-linked peptides provide no information about secondary structure. (ii) A protein chain can be folded in multiple ways to create a best fit. (iii) Ad hoc folding of a secondary structure is unlikely to produce a stable orientation of hydrophobic and hydrophilic residues. To address these limitations, we used a different approach. We first noted that the dimeric apoA-I crystal structure, (Δ185–243)apoA-I, is topologically identical to a monomer in which helix 5 forms a helical hairpin, a monomer with a hydrophobic cleft running the length of the molecule. We then realized that a second crystal structure, (Δ1–43)apoA-I, contains a C-terminal structure that fits snuggly via aromatic and hydrophobic interactions into the hydrophobic cleft. Consequently, we combined these crystal structures into an initial model that was subjected to molecular dynamics simulations. We tested the initial and simulated models and the two previously published models in three ways: against two published data sets (domains predicted to be helical by H/D exchange and six spin-coupled residues) and against our own experimentally determined cross-linking distance constraints. We note that the best fit simulation model, superior by all tests to previously published models, has dynamic features of a molten globule with interesting implications for the functions of apoA-I. PMID:25423138

Mitochondrial CHCHD-Containing Proteins: Physiologic Functions and Link with Neurodegenerative Diseases.

PubMed

Zhou, Zhi-Dong; Saw, Wuan-Ting; Tan, Eng-King

2017-09-01

The coiled-coil-helix-coiled-coil-helix domain (CHCHD)-containing proteins are evolutionarily conserved nucleus-encoded small mitochondrial proteins with important functions. So far, nine members have been identified in this protein family. All CHCHD proteins have at least one functional coiled-coil-helix-coiled-coil-helix (CHCH) domain, which is stabilized by two pairs of disulfide bonds between two helices. CHCHD proteins have various important pathophysiological roles in mitochondria and other key cellular processes. Mutations of CHCHD proteins have been associated with various human neurodegenerative diseases. Mutations of CHCHD10 are associated with amyotrophic lateral sclerosis (ALS) and/or frontotemporal lobe dementia (FTD), motor neuron disease, and late-onset spinal muscular atrophy and autosomal dominant mitochondrial myopathy. CHCHD10 stabilizes mitochondrial crista ultrastructure and maintains its integrity. In patients with CHCHD10 mutations, there are abnormal mitochondrial crista structure, deficiencies of respiratory chain complexes, impaired mitochondrial respiration, and multiple mitochondrial DNA (mtDNA) deletions. Recently, CHCHD2 mutations are linked with autosomal dominant and sporadic Parkinson's disease (PD). The CHCHD2 is a multifunctional protein and plays roles in regulation of mitochondrial metabolism, synthesis of respiratory chain components, and modulation of cell apoptosis. With a better understanding of the pathophysiologic roles of CHCHD proteins, they may be potential novel therapeutic targets for human neurodegenerative diseases.

Identification of the NC1 domain of {alpha}3 chain as critical for {alpha}3{alpha}4{alpha}5 type IV collagen network assembly.

PubMed

LeBleu, Valerie; Sund, Malin; Sugimoto, Hikaru; Birrane, Gabriel; Kanasaki, Keizo; Finan, Elizabeth; Miller, Caroline A; Gattone, Vincent H; McLaughlin, Heather; Shield, Charles F; Kalluri, Raghu

2010-12-31

The network organization of type IV collagen consisting of α3, α4, and α5 chains in the glomerular basement membrane (GBM) is speculated to involve interactions of the triple helical and NC1 domain of individual α-chains, but in vivo evidence is lacking. To specifically address the contribution of the NC1 domain in the GBM collagen network organization, we generated a mouse with specific loss of α3NC1 domain while keeping the triple helical α3 chain intact by connecting it to the human α5NC1 domain. The absence of α3NC1 domain leads to the complete loss of the α4 chain. The α3 collagenous domain is incapable of incorporating the α5 chain, resulting in the impaired organization of the α3α4α5 chain-containing network. Although the α5 chain can assemble with the α1, α2, and α6 chains, such assembly is incapable of functionally replacing the α3α4α5 protomer. This novel approach to explore the assembly type IV collagen in vivo offers novel insights in the specific role of the NC1 domain in the assembly and function of GBM during health and disease.

Induced liquid-crystalline ordering in solutions of stiff and flexible amphiphilic macromolecules: Effect of mixture composition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glagolev, Mikhail K.; Vasilevskaya, Valentina V., E-mail: vvvas@polly.phys.msu.ru; Khokhlov, Alexei R.

Impact of mixture composition on self-organization in concentrated solutions of stiff helical and flexible macromolecules was studied by means of molecular dynamics simulation. The macromolecules were composed of identical amphiphilic monomer units but a fraction f of macromolecules had stiff helical backbones and the remaining chains were flexible. In poor solvents the compacted flexible macromolecules coexist with bundles or filament clusters from few intertwined stiff helical macromolecules. The increase of relative content f of helical macromolecules leads to increase of the length of helical clusters, to alignment of clusters with each other, and then to liquid-crystalline-like ordering along a singlemore » direction. The formation of filament clusters causes segregation of helical and flexible macromolecules and the alignment of the filaments induces effective liquid-like ordering of flexible macromolecules. A visual analysis and calculation of order parameter relaying the anisotropy of diffraction allow concluding that transition from disordered to liquid-crystalline state proceeds sharply at relatively low content of stiff components.« less

Toda-Lattice Solitons in α-Helical Proteins

NASA Astrophysics Data System (ADS)

Yomosa, Shigeo

1984-10-01

We propose a theory of Toda-lattice soliton in α-helical proteins which enables us to elucidate the molecular dynamics of muscle contraction. One-dimensional chain of peptide groups jointed together by H-bonds, which stabilizes α-helical structure of proteins, can be regarded as a Toda-lattice where the potential of H-bonding interaction between peptide groups has a remarkable nonlinearity. By using the results of theoretical studies for Toda-lattice soliton and for the initial value problem, we can describe the molecular mechanism of the transformation of the chemical energy to the mechanical work in the process of the muscle contraction.

Effect of proline kinks on the mechanical unfolding of α-helices

NASA Astrophysics Data System (ADS)

Arteca, Gustavo A.; Li, Zhiying

2004-12-01

Proteins unfold by applying an external force, although the microscopic mechanism is still not well understood. In this work, we use steered molecular dynamics to probe fundamental aspects of the stretching transition of α-helices, in particular how proline kinks and side chain dynamics would influence their ability to resist the applied force. We find that proline residues effectively 'cut' a helix in half when introduced on stable homopolymers, whereas their effect is smaller when present in helices that are more easily deformed. Our findings provide insight into the factors that may regulate the mechanical stretching of realistic protein domains.

General split helicity gluon tree amplitudes in open twistor string theory

NASA Astrophysics Data System (ADS)

Dolan, Louise; Goddard, Peter

2010-05-01

We evaluate all split helicity gluon tree amplitudes in open twistor string theory. We show that these amplitudes satisfy the BCFW recurrence relations restricted to the split helicity case and, hence, that these amplitudes agree with those of gauge theory. To do this we make a particular choice of the sextic constraints in the link variables that determine the poles contributing to the contour integral expression for the amplitudes. Using the residue theorem to re-express this integral in terms of contributions from poles at rational values of the link variables, which we determine, we evaluate the amplitudes explicitly, regaining the gauge theory results of Britto et al. [25].

Intrinsic two-dimensional states on the pristine surface of tellurium

NASA Astrophysics Data System (ADS)

Li, Pengke; Appelbaum, Ian

2018-05-01

Atomic chains configured in a helical geometry have fascinating properties, including phases hosting localized bound states in their electronic structure. We show how the zero-dimensional state—bound to the edge of a single one-dimensional helical chain of tellurium atoms—evolves into two-dimensional bands on the c -axis surface of the three-dimensional trigonal bulk. We give an effective Hamiltonian description of its dispersion in k space by exploiting confinement to a virtual bilayer, and elaborate on the diminished role of spin-orbit coupling. These intrinsic gap-penetrating surface bands were neglected in the interpretation of seminal experiments, where two-dimensional transport was otherwise attributed to extrinsic accumulation layers.

Single amino acid mutation in alpha-helical peptide affect second harmonic generation hyperpolarizability

NASA Astrophysics Data System (ADS)

Wei, Jing; Wang, Jin-Yun; Zhang, Min-Yi; Chai, Guo-Liang; Lin, Chen-Sheng; Cheng, Wen-Dan

2013-01-01

We investigate the effect of side chain on the first-order hyperpolarizability in α-helical polyalanine peptide with the 10th alanine mutation (Acetyl(ala)9X(ala)7NH2). Structures of various substituted peptides are optimized by ONIOM (DFT: AM1) scheme, and then linear and nonlinear optical properties are calculated by SOS//CIS/6-31G∗ method. The polarizability and first-order hyperpolarizability increase obviously only when 'X' represents phenylalanine, tyrosine and tryptophan. We also discuss the origin of nonlinear optical response and determine what caused the increase of first-order hyperpolarizability. Our results strongly suggest that side chains containing benzene, phenol and indole have important contributions to first-order hyperpolarizability.

Modeling the Structure of Helical Assemblies with Experimental Constraints in Rosetta.

PubMed

André, Ingemar

2018-01-01

Determining high-resolution structures of proteins with helical symmetry can be challenging due to limitations in experimental data. In such instances, structure-based protein simulations driven by experimental data can provide a valuable approach for building models of helical assemblies. This chapter describes how the Rosetta macromolecular package can be used to model homomeric protein assemblies with helical symmetry in a range of modeling scenarios including energy refinement, symmetrical docking, comparative modeling, and de novo structure prediction. Data-guided structure modeling of helical assemblies with experimental information from electron density, X-ray fiber diffraction, solid-state NMR, and chemical cross-linking mass spectrometry is also described.

Crystal structures of 5-amino-N-phenyl-3H-1,2,4-di-thia-zol-3-iminium chloride and 5-amino-N-(4-chloro-phen-yl)-3H-1,2,4-di-thia-zol-3-iminium chloride monohydrate.

PubMed

Yeo, Chien Ing; Tan, Yee Seng; Tiekink, Edward R T

2015-10-01

The crystal and mol-ecular structures of the title salt, C8H8N3S2 (+)·Cl(-), (I), and salt hydrate, C8H7ClN3S2 (+)·Cl(-)·H2O, (II), are described. The heterocyclic ring in (I) is statistically planar and forms a dihedral angle of 9.05 (12)° with the pendant phenyl ring. The comparable angle in (II) is 15.60 (12)°, indicating a greater twist in this cation. An evaluation of the bond lengths in the H2N-C-N-C-N sequence of each cation indicates significant delocalization of π-electron density over these atoms. The common feature of the crystal packing in (I) and (II) is the formation of charge-assisted amino-N-H⋯Cl(-) hydrogen bonds, leading to helical chains in (I) and zigzag chains in (II). In (I), these are linked by chains mediated by charge-assisted iminium-N(+)-H⋯Cl(-) hydrogen bonds into a three-dimensional architecture. In (II), the chains are linked into a layer by charge-assisted water-O-H⋯Cl(-) and water-O-H⋯O(water) hydrogen bonds with charge-assisted iminium-N(+)-H⋯O(water) hydrogen bonds providing the connections between the layers to generate the three-dimensional packing. In (II), the chloride anion and water mol-ecules are resolved into two proximate sites with the major component being present with a site occupancy factor of 0.9327 (18).

Signatures of unfolding in the early stages of protein denaturation

NASA Astrophysics Data System (ADS)

Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

2012-04-01

A comparative study of the early stages of unfolding of five proteins: cyt c, c-b 562, cyt c‧, azurin, and lysozyme is reported. From crystallographic data, helical regions and intervening non-helical (or 'turning') regions are identified in each. Exploiting a previously introduced geometrical model, the paper describes quantitatively the stepwise extension of a polypeptide chain subject to the geometrical constraint that the spatial relationship among the residues of each triplet is fixed by native-state crystallographic data. Despite differences among the above-cited proteins, remarkable universality of behavior is found in the early stages of unfolding. At the very earliest stages, internal residues in each helical region have a common unfolding history; the terminal residues, however, are extraordinarily sensitive to structural perturbations. Residues in non-helical sections of the polypeptide unfold after residues in the internal helical regions, but with increasing steric perturbation playing a dominant role in advancing denaturation.

Homoallylglycine residues are superior precursors to orthogonally modified thioether containing polypeptides.

PubMed

Perlin, Pesach; Gharakhanian, Eric G; Deming, Timothy J

2018-06-12

Homoallylglycine N-carboxyanhydride, Hag NCA, monomers were synthesized and used to prepare polypeptides containing Hag segments with controllable lengths of up to 245 repeats. Poly(l-homoallylglycine), GHA, was found to adopt an α-helical conformation, which provided good solubility in organic solvents and allowed high yield functionalization of its alkene side-chains via radical promoted addition of thiols. The conformations of these derivatives were shown to be switchable between α-helical and disordered states in aqueous media using thioether alkylation or oxidation reactions. Incorporation of GHA segments into block copolymers with poly(l-methionine), M, segments provided a means to orthogonally modify thioether side-chains different ways in separate copolypeptide domains. This approach allows preparation of functional polypeptides containing discrete domains of oxidized and alkylated thioether containing residues, where chain conformation and functionality of each domain can be independently modified.

Three-dimensional crystal structure of recombinant murine interferon-beta.

PubMed Central

Senda, T; Shimazu, T; Matsuda, S; Kawano, G; Shimizu, H; Nakamura, K T; Mitsui, Y

1992-01-01

The crystal structure of recombinant murine interferon-beta (IFN-beta) has been solved by the multiple isomorphous replacement method and refined to an R-factor of 20.5% against 2.6 A X-ray diffraction data. The structure shows a variant of the alpha-helix bundle with a new chain-folding topology, which seems to represent a basic structural framework of all the IFN-alpha and IFN-beta molecules belonging to the type I family. Functionally important segments of the polypeptide chain, as implied through numerous gene manipulation studies carried out so far, are spatially clustered indicating the binding site(s) to the receptor(s). Comparison of the present structure with those of other alpha-helical cytokine proteins, including porcine growth hormone, interleukin 2 and interferon gamma, indicated either a topological similarity in chain folding or a similar spatial arrangement of the alpha-helices. Images PMID:1505514

Interacting helical surfaces of the transmembrane segments of subunits a and c' of the yeast V-ATPase defined by disulfide-mediated cross-linking.

PubMed

Kawasaki-Nishi, Shoko; Nishi, Tsuyoshi; Forgac, Michael

2003-10-24

Proton translocation by the vacuolar (H+)-ATPase (or V-ATPase) has been shown by mutagenesis to be dependent upon charged residues present within transmembrane segments of subunit a as well as the three proteolipid subunits (c, c', and c"). Interaction between R735 in TM7 of subunit a and the glutamic acid residue in the middle of TM4 of subunits c and c' or TM2 of subunit c" has been proposed to be essential for proton release to the luminal compartment. In order to determine whether the helical face of TM7 of subunit a containing R735 is capable of interacting with the helical face of TM4 of subunit c' containing the essential glutamic acid residue (Glu-145), cysteine-mediated cross-linking between these subunits in yeast has been performed. Cys-less forms of subunits a and c' as well as forms containing unique cysteine residues were constructed, introduced together into a strain disrupted in both endogenous subunits, and tested for growth at neutral pH, for assembly competence and for cross-linking in the presence of cupric-phenanthroline by SDS-PAGE and Western blot analysis. Four different cysteine mutants of subunit a were each tested pairwise with ten different unique cysteine mutants of subunit c'. Strong cross-linking was observed for the pairs aS728C/c'I142C, aA731C/c'E145C, aA738C/c'F143C, aA738C/c'L147C, and aL739C/c'L147C. Partial cross-linking was observed for an additional 13 of 40 pairs analyzed. When arrayed on a helical wheel diagram, the results suggest that the helical face of TM7 of subunit a containing Arg-735 interacts with the helical face of TM4 of subunit c' centered on Val-146 and bounded by Glu-145 and Leu-147. The results are consistent with a possible rotational flexibility of one or both of these transmembrane segments as well as some flexibility of movement perpendicular to the membrane.

Synthesis, crystal structures, and luminescent properties of Cd(II) coordination polymers assembled from semi-rigid multi-dentate N-containing ligand

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Gang; Shao, Kui-Zhan; Chen, Lei

2012-12-15

Three new polymers, [Cd(L){sub 2}(H{sub 2}O){sub 2}]{sub n} (1), [Cd{sub 3}(L){sub 2}({mu}{sub 3}-OH){sub 2}({mu}{sub 2}-Cl){sub 2}(H{sub 2}O){sub 2}]{sub n} (2), {l_brace}[Cd{sub 2}(L){sub 2}(nic){sub 2}(H{sub 2}O){sub 2}]{center_dot}H{sub 2}O{r_brace}{sub n} (3) (HL=5-(4-((1H-1,2,4-triazol-1-yl)methyl)phenyl)-1H-tetrazole, Hnic=nicotinic acid) have been prepared and structurally characterized. Compounds 1 and 2 display 2D monomolecular layers built by the inter-linking single helical chains and L{sup -} ligands connecting chain-like [Cd({mu}{sub 3}-OH)({mu}{sub 2}-Cl)]{sub n} secondary building units, respectively. Compound 3 is constructed from the mixed ligands and possesses a (3,4)-connected framework with (4{center_dot}8{sup 2})(4{center_dot}8{sup 2}{center_dot}10{sup 3}) topology. Moreover, the fluorescent properties of HL ligand and compounds 1-3 are also been investigated.more » - Graphical abstract: Three new coordination polymers based on the semi-rigid multidentate N-donor ligand have been successfully synthesized by hydrothermal reaction. Complexes 1 and 2 exhibit the 2D layers formed by inter-linking single helices and L{sup -} anions bridging 1D chain-like SBUs, respectively. Complex 3 is buit by L{sup -} and assistant nic{sup -} ligands connecting metal centers and possesses a (3,4)-connected framework with (4 Multiplication-Sign 8{sup 2})(4 Multiplication-Sign 8{sup 2} Multiplication-Sign 10{sup 3}) topology. Moreover, these complexes display fluorescent properties indicating that they may have potential applications as optical materials. Highlights: Black-Right-Pointing-Pointer Three Cd-compounds were prepared from semi-rigid HL ligand with different N-containing groups. Black-Right-Pointing-Pointer They exhibit diverse structures from 2D monomolecular layer to 3D covalent framework. Black-Right-Pointing-Pointer The HL ligands displayed various coordination modes under different reaction conditions. Black-Right-Pointing-Pointer These compounds exhibit good luminescent properties.« less

Homochiral coordination polymers with helixes and metal clusters based on lactate derivatives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Zhong-Xuan, E-mail: xuzhongxuan4201@163.com; Ma, Yu-Lu; Lv, Guo-ling

2017-05-15

Utilizing the lactic acid derivatives (R)-4-(1-carboxyethoxy)benzoic acid (denoted: (R)-H{sub 2}CBA) and (S)-4-(1-carboxyethoxy)benzoic acid (denoted: (S)-H{sub 2}CBA)as chiral linkers to self-assemble with 4, 4′-bipyridine (denoted: BIP) and Cd(II) ions, a couple of three-dimensional homochiral coordination polymers, namely [Cd{sub 3}((R)-CBA){sub 3} (BIP){sub 2}(H{sub 2}O)]·xGuest (1-D) and [Cd{sub 3}((S)-CBA){sub 3}(BIP){sub 2}(H{sub 2}O)]·xGuest (1-L), have been synthesized under solvothermal reaction condition. Single crystal X-ray diffraction analysis reveals the two complexes contain single helical chains based on enantiopure ligands and cadmium clusters. Moreover, some physical characteristics such as PXRD, thermal stability, solid-state circular dichroism (CD) and luminescent were also investigated. - Graphical abstract: Utilizing enantiomericmore » lactic acid derivatives (R)-H{sub 2}CBA and (S)-H{sub 2}CBA to assemble with Cd{sup 2+} ions and ancillary BIP ligands, a couple of 3D homochiral coordination polymers with metal clusters and helical chains have been prepared by hydrothermal reaction. - Highlights: • Chiral lactic acid derivative. • Enantiomeric coordination polymer. • Helical chain. • Trinuclear cadmium cluster.« less

Two new frameworks of potassium saccharate obtained from acidic and alkaline solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lv, Yao-Kang; Feng, Yun-Long, E-mail: sky37@zjnu.edu.c; Liu, Ji-Wei

2011-05-15

Two chiral K(I) complexes based on D-saccharic acid (H{sub 2}sac), [K(Hsac)]{sub n} (1) and [K{sub 2}(sac)]{sub n} (2) were obtained from acidic and alkaline solution. The 3D framework of 1 includes K(I) polyhedral rods and typical pairwise coaxial right- and left-handed helical chains, and displays binodal 6-connected pcu topology. 2 contains 2D polyhedral sheets consisting of left-handed helical chains, and generates 3D network with an unprecedented (7,11)-connected net. Cyclic voltammetry tests and charge-discharge tests indicate that the addition of complex 2 to the electrolyte could improve the electrochemical properties of the nickel hydroxide electrode. -- Graphical abstract: Two K(I) complexesmore » based on D-saccharic acid (H{sub 2}sac), [K(Hsac)]{sub n} (1) and [K{sub 2}(sac)]{sub n} (2) were obtained and characterized. Electrochemical studies indicate the potential use of 2 in Ni-MH battery. Display Omitted highlights: > Two novel chiral K(I) frameworks based on D-saccharic acid were obtained. > The structure of 1 includes K(I) polyhedral rods and typical helical chains. > 2 contains 2D polyhedral sheets and generates an unprecedented (7,11)-connected net. > Addition of 2 to electrolyte could improve the nickel hydroxide electrode's property.« less

Water-stable helical structure of tertiary amides of bicyclic β-amino acid bearing 7-azabicyclo[2.2.1]heptane. Full control of amide cis-trans equilibrium by bridgehead substitution.

PubMed

Hosoya, Masahiro; Otani, Yuko; Kawahata, Masatoshi; Yamaguchi, Kentaro; Ohwada, Tomohiko

2010-10-27

Helical structures of oligomers of non-natural β-amino acids are significantly stabilized by intramolecular hydrogen bonding between main-chain amide moieties in many cases, but the structures are generally susceptible to the environment; that is, helices may unfold in protic solvents such as water. For the generation of non-hydrogen-bonded ordered structures of amides (tertiary amides in most cases), control of cis-trans isomerization is crucial, even though there is only a small sterical difference with respect to cis and trans orientations. We have established methods for synthesis of conformationally constrained β-proline mimics, that is, bridgehead-substituted 7-azabicyclo[2.2.1]heptane-2-endo-carboxylic acids. Our crystallographic, 1D- and 2D-NMR, and CD spectroscopic studies in solution revealed that a bridgehead methoxymethyl substituent completely biased the cis-trans equilibrium to the cis-amide structure along the main chain, and helical structures based on the cis-amide linkage were generated independently of the number of residues, from the minimalist dimer through the tetramer, hexamer, and up to the octamer, and irrespective of the solvent (e.g., water, alcohol, halogenated solvents, and cyclohexane). Generality of the control of the amide equilibrium by bridgehead substitution was also examined.

Crystal structures and thermodynamics/kinetics of Zn(II) coordination polymers with helical chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Tian; Yue, Ke-Fen, E-mail: ykflyy@nwu.edu.cn; Zhao, Yi-xing

Solvothermal reactions of Zn(II) acetates and four V-shaped carboxylates ligands in the presence of 1,4-Bis(2-methyl-imidazol-1-yl)butane afforded four interesting Zn(II) coordination polymers with helical chains, namely, {[Zn(bib)(atibdc)]·2H_2O}{sub n} (1), {[Zn(bib)(atbip)]·H_2O}{sub n} (2), {[Zn(bib)(2,2′-tda)]}{sub n} (3) and {[Zn(bib)(5-tbipa)]·EtOH}{sub n} (4), (H{sub 2}atibdc=5-amino-2,4,6-triiodoisophthalic acid, H{sub 2}atbip=5-amino-2,4,6-tribromoisophthalic acid, 2,2′-H{sub 2}tad=2,2′-thiodiacetic acid, 5-H{sub 2}tbipa=5-tert-butyl-isophthalic acid). 1 reveals a 3D chiral framework with three kinds of helical chains along a, b and c axis. 2 shows a 2D step-type chiral framework with right-handed helical chains. 3 displays a wavelike 2D layer network possessing alternate left- and right-handed helical chains. 4 presents a four-connected 3D framework withmore » zigzag and meso-helical chains. The different spacers and substituent group of carboxylic acid ligands may lead to the diverse network structures of 1–4. The fluorescent properties of complexes 1−4 were studied. In addition, the thermal decompositions properties of 1–4 were investigated by simultaneous TG/DTG–DSC technique. The apparent activation energy E and the pre-exponential factor (A) of skeleton collapse for the complexes 1–4 are calculated by the integral Kissinger's method and Ozawa–Doyle's method. The activation energy E (E{sub 1}=209.658 kJ·mol{sup −1}, E{sub 2}=250.037 kJ mol{sup −1}, E{sub 3}=225.300 kJ mol{sup −1}, E{sub 4}=186.529 kJ·mol{sup −1}) demonstrates that the reaction rate of the melting decomposition is slow. The thermodynamic parameters (ΔH{sup ‡}, ΔG{sup ‡} and ΔS{sup ‡}) at the peak temperatures of the DTG curves were also calculated. ΔG{sup ‡}>0 indicates that the skeleton collapse is not spontaneous. ΔH{sub d}>0 suggests that the skeleton collapse is endothermic, corresponding to the intense endothermic peak of the DSC curve. The structural stability could be illustrated from the point of thermodynamics and kinetics. - Graphical abstract: Four new zinc coordination architectures constructed from the primary ligand bib, transition metal ions Zn(II) and four V-shaped carboxylate coligands. The different structural evolutions of complexes 1–4 have systematically illustrated that the carboxylate coligands play a critical role in the assemblies of the CPs. Their thermal decompositions properties of 1–4 were investigated by simultaneous TG/DTG–DSC technique. The apparent activation energy E and the pre-exponential factor (A) of skeleton collapse for the complexes 1−4 are calculated by the integral Kissinger’s method and Ozawa–Doyle’s method. The structural stability could be illustrated from the point of thermodynamics and kinetics. Display Omitted.« less

Magnetic anisotropy in the frustrated spin-chain compound β - TeVO 4

DOE PAGES

Weickert, F.; Harrison, Neil; Scott, Brian Lindley; ...

2016-08-01

In this paper, isotropic and anisotropic magnetic behavior of the frustrated spin-chain compound β-TeVO 4 is reported. Three magnetic transitions observed in zero magnetic field are tracked in fields applied along different crystallographic directions using magnetization, heat capacity, and magnetostriction measurements. Qualitatively different temperature-field diagrams are obtained below 10 T for the field applied along a or b and along c, respectively. In contrast, a nearly isotropic high-field phase emerges above 18 T and persists up to the saturation that occurs around 22.5 T. Upon cooling in low fields, the transitions at T N1 and T N2 toward the spin-density-wavemore » and stripe phases are of the second order, whereas the transition at T N3 toward the helical state is of the first order and entails a lattice component. Our microscopic analysis identifies frustrated J 1-J 2 spin chains with a sizable antiferromagnetic interchain coupling in the bc plane and ferromagnetic couplings along the a direction. The competition between these ferromagnetic interchain couplings and the helical order within the chain underlies the incommensurate order along the a direction, as observed experimentally. While a helical state is triggered by the competition between J 1 and J 2 within the chain, the plane of the helix is not uniquely defined because of competing magnetic anisotropies. Finally, using high-resolution synchrotron diffraction and 125Te nuclear magnetic resonance, we also demonstrate that the crystal structure of β-TeVO 4 does not change down to 10 K, and the orbital state of V 4+ is preserved.« less

Molecular dynamics simulations of fluoropolymers in the solid state

NASA Astrophysics Data System (ADS)

Holt, David Bryan

1998-10-01

Molecular mechanics and dynamics simulations have been utilized to address the behavior of helix reversal defects in fluoropolymers. The results of the simulations confirm that helix reversals do form and migrate in PTFE crystals. The most important defect structure is a helix reversal band: two helix reversals which bracker a small chain segment (typically 6-7 backbone atoms) having the opposite helical sense from the parent molecule. Small reversal bands had velocities ranging between 100 m/s (low temperature)-250 m/s (high temperature). The size of this reversal band defect is dependent upon the helical conformation and is equal to approximately half of the helical repeat unit in the low and intermediate temperature phases. In the high temperature phase where intermolecular effects are diminished, a wider distribution of reversal band sizes was observed during the simulations. A mechanism is identified by which significant reorientation of a chain segment about the molecular axis can occur when it is bracketed by two helix reversal bands. Simulations with a model containing a perfluoromethyl (PFM) group at low temperature showed that the presence of the PFM group significantly restricts chain mobility locally. However, a significant reduction in the helix reversal defect density was observed on neighboring chains as well. During simulations in which a shear deformation was applied to the models with and without a PFM group, an increase in reversal defect density was observed. However, the helix reversal density in the sheared model containing the PFM branch was less than that in the model without a PFM branch under no shear. These data implicate helix reversal defects and associated chain segment motions in the mechanical behavior of fluoropolymer materials.

The role of protein homochirality in shaping the energy landscape of folding

PubMed Central

Nanda, Vikas; Andrianarijaona, Aina; Narayanan, Chitra

2007-01-01

The homochirality, or isotacticity, of the natural amino acids facilitates the formation of regular secondary structures such as α-helices and β-sheets. However, many examples exist in nature where novel polypeptide topologies use both l- and d-amino acids. In this study, we explore how stereochemistry of the polypeptide backbone influences basic properties such as compactness and the size of fold space by simulating both lattice and all-atom polypeptide chains. We formulate a rectangular lattice chain model in both two and three dimensions, where monomers are chiral, having the effect of restricting local conformation. Syndiotactic chains with alternating chirality of adjacent monomers have a very large ensemble of accessible conformations characterized predominantly by extended structures. Isotactic chains on the other hand, have far fewer possible conformations and a significant fraction of these are compact. Syndiotactic chains are often unable to access maximally compact states available to their isotactic counterparts of the same length. Similar features are observed in all-atom models of isotactic versus syndiotactic polyalanine. Our results suggest that protein isotacticity has evolved to increase the enthalpy of chain collapse by facilitating compact helical states and to reduce the entropic cost of folding by restricting the size of the unfolded ensemble of competing states. PMID:17600146

Precise side-chain conformation analysis of L-phenylalanine in α-helical polypeptide by quantum-chemical calculation and 13C CP-MAS NMR measurement

NASA Astrophysics Data System (ADS)

Niimura, Subaru; Suzuki, Junya; Kurosu, Hiromichi; Yamanobe, Takeshi; Shoji, Akira

2010-04-01

To clarify the positive role of side-chain conformation in the stability of protein secondary structure (main-chain conformation), we successfully calculated the optimization structure of a well-defined α-helical octadecapeptide composed of L-alanine (Ala) and L-phenylalanine (Phe) residues, H-(Ala) 8-Phe-(Ala) 9-OH, based on the molecular orbital calculation with density functional theory (DFT/B3LYP/6-31G(d)). From the total energy and the precise secondary structural parameters such as main-chain dihedral angles and hydrogen-bond parameters of the optimized structure, we confirmed that the conformational stability of an α-helix is affected dominantly by the side-chain conformation ( χ1) of the Phe residue in this system: model A ( T form: around 180° of χ1) is most stable in α-helix and model B ( G + form: around -60° of χ1) is next stable, but model C ( G - form: around 60° of χ1) is less stable. In addition, we demonstrate that the stable conformation of poly( L-phenylalanine) is an α-helix with the side-chain T form, by comparison of the carbonyl 13C chemical shift measured by 13C CP-MAS NMR and the calculated one.

Left-handed helical preference in an achiral peptide chain is induced by an L-amino acid in an N-terminal type II β-turn.

PubMed

De Poli, Matteo; De Zotti, Marta; Raftery, James; Aguilar, Juan A; Morris, Gareth A; Clayden, Jonathan

2013-03-15

Oligomers of the achiral amino acid Aib adopt helical conformations in which the screw-sense may be controlled by a single N-terminal residue. Using crystallographic and NMR techniques, we show that the left- or right-handed sense of helical induction arises from the nature of the β-turn at the N terminus: the tertiary amino acid L-Val induces a left-handed type II β-turn in both the solid state and in solution, while the corresponding quaternary amino acid L-α-methylvaline induces a right-handed type III β-turn.

Structure of a short-chain dehydrogenase/reductase (SDR) within a genomic island from a clinical strain of Acinetobacter baumannii

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shah, Bhumika S., E-mail: bhumika.shah@mq.edu.au; Tetu, Sasha G.; Harrop, Stephen J.

2014-09-25

The structure of a short-chain dehydrogenase encoded within genomic islands of A. baumannii strains has been solved to 2.4 Å resolution. This classical SDR incorporates a flexible helical subdomain. The NADP-binding site and catalytic side chains are identified. Over 15% of the genome of an Australian clinical isolate of Acinetobacter baumannii occurs within genomic islands. An uncharacterized protein encoded within one island feature common to this and other International Clone II strains has been studied by X-ray crystallography. The 2.4 Å resolution structure of SDR-WM99c reveals it to be a new member of the classical short-chain dehydrogenase/reductase (SDR) superfamily. Themore » enzyme contains a nucleotide-binding domain and, like many other SDRs, is tetrameric in form. The active site contains a catalytic tetrad (Asn117, Ser146, Tyr159 and Lys163) and water molecules occupying the presumed NADP cofactor-binding pocket. An adjacent cleft is capped by a relatively mobile helical subdomain, which is well positioned to control substrate access.« less

Homochiral Evolution in Self-Assembled Chiral Polymers and Block Copolymers.

PubMed

Wen, Tao; Wang, Hsiao-Fang; Li, Ming-Chia; Ho, Rong-Ming

2017-04-18

The significance of chirality transfer is not only involved in biological systems, such as the origin of homochiral structures in life but also in man-made chemicals and materials. How the chiral bias transfers from molecular level (molecular chirality) to helical chain (conformational chirality) and then to helical superstructure or phase (hierarchical chirality) from self-assembly is vital for the chemical and biological processes in nature, such as communication, replication, and enzyme catalysis. In this Account, we summarize the methodologies for the examination of homochiral evolution at different length scales based on our recent studies with respect to the self-assembly of chiral polymers and chiral block copolymers (BCPs*). A helical (H*) phase to distinguish its P622 symmetry from that of normal hexagonally packed cylinder phase was discovered in the self-assembly of BCPs* due to the chirality effect on BCP self-assembly. Enantiomeric polylactide-containing BCPs*, polystyrene-b-poly(l-lactide) (PS-PLLA) and polystyrene-b-poly(d-lactide) (PS-PDLA), were synthesized for the examination of homochiral evolution. The optical activity (molecular chirality) of constituted chiral repeating unit in the chiral polylactide is detected by electronic circular dichroism (ECD) whereas the conformational chirality of helical polylactide chain can be explicitly determined by vibrational circular dichroism (VCD). The H* phases of the self-assembled polylactide-containing BCPs* can be directly visualized by 3D transmission electron microscopy (3D TEM) technique at which the handedness (hierarchical chirality) of the helical nanostructure is thus determined. The results from the ECD, VCD, and 3D TEM for the investigated chirality at different length scales suggest the homochiral evolution in the self-assembly of the BCPs*. For chiral polylactides, twisted lamellae in crystalline banded spherulite can be formed by dense packing scheme and effective interactions upon helical chains from self-assembly. The handedness of the twisted lamella can be determined by using rotation experiment of polarized light microscopy (PLM). Similar to the self-assembly of BCPs*, the examined results suggest the homochiral evolution in the crystallized chiral polylactides. The results presented in this Account demonstrate the notable progress in the spectral and morphological determination for the examination of molecular, conformational, and hierarchical chirality in self-assembled twisted superstructures of chiral polymers and helical phases of block copolymers and suggest the attainability of homochiral evolution in the self-assembly of chiral homopolymers and BCPs*. The suggested methodologies for the understanding of the mechanisms of the chirality transfer at different length scales provide the approaches to give Supporting Information for disclosing the mysteries of the homochiral evolution from molecular level.

Novel Structures of Self-Associating Stapled Peptides

PubMed Central

Bhattacharya, Shibani; Zhang, Hongtao; Cowburn, David; Debnath, Asim K.

2012-01-01

Hydrocarbon stapling of peptides is a powerful technique to transform linear peptides into cell-permeable helical structures that can bind to specific biological targets. In this study, we have used high resolution solution NMR techniques complemented by Dynamic Light Scattering to characterize extensively a family of hydrocarbon stapled peptides with known inhibitory activity against HIV-1 capsid assembly to evaluate the various factors that modulate activity. The helical peptides share a common binding motif but differ in charge, the length and position of the staple. An important outcome of the study was to show the peptides share a propensity to self-associate into organized polymeric structures mediated predominantly by hydrophobic interactions between the olefinic chain and the aromatic side-chains from the peptide. We have also investigated in detail the structural significance of the length and position of the staple, and of olefinic bond isomerization in stabilizing the helical conformation of the peptides as potential factors driving polymerization. This study presents the numerous challenges of designing biologically active stapled peptides and the conclusions have broad implications for optimizing a promising new class of compounds in drug discovery. PMID:22170623

Self-assembly of Janus particles into helices with tunable pitch

NASA Astrophysics Data System (ADS)

Fernández, M. Sobrino; Misko, V. R.; Peeters, F. M.

2015-10-01

Janus particles present an important class of building blocks for directional assembly. These are compartmentalized colloids with two different hemispheres. In this work we consider a three-dimensional model of Janus spheres that contain one hydrophobic and one charged hemisphere. Using molecular dynamics simulations, we study the morphology of these particles when confined in a channel-like environment. The interplay between the attractive and repulsive forces on each particle gives rise to a rich phase space where the relative orientation of each particle plays a dominant role in the formation of large-scale clusters. The interest in this system is primarily due to the fact that it could give a better understanding of the mechanisms of the formation of polar membranes. A variety of ordered membranelike morphologies is found consisting of single and multiple connected chain configurations. The helicity of these chains can be chosen by simply changing the salt concentration of the solution. Special attention is given to the formation of Bernal spirals. These helices are composed of regular tetrahedra and are known to exhibit nontrivial translational and rotational symmetry.

Charge transfer in model peptides: obtaining Marcus parameters from molecular simulation.

PubMed

Heck, Alexander; Woiczikowski, P Benjamin; Kubař, Tomáš; Giese, Bernd; Elstner, Marcus; Steinbrecher, Thomas B

2012-02-23

Charge transfer within and between biomolecules remains a highly active field of biophysics. Due to the complexities of real systems, model compounds are a useful alternative to study the mechanistic fundamentals of charge transfer. In recent years, such model experiments have been underpinned by molecular simulation methods as well. In this work, we study electron hole transfer in helical model peptides by means of molecular dynamics simulations. A theoretical framework to extract Marcus parameters of charge transfer from simulations is presented. We find that the peptides form stable helical structures with sequence dependent small deviations from ideal PPII helices. We identify direct exposure of charged side chains to solvent as a cause of high reorganization energies, significantly larger than typical for electron transfer in proteins. This, together with small direct couplings, makes long-range superexchange electron transport in this system very slow. In good agreement with experiment, direct transfer between the terminal amino acid side chains can be dicounted in favor of a two-step hopping process if appropriate bridging groups exist. © 2012 American Chemical Society

Unfolding four-helix bundles

NASA Astrophysics Data System (ADS)

Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

2011-03-01

A geometrical model has been developed to describe the early stages of unfolding of cytochromes c‧ and c-b562 . Calculations are based on a step-wise extension of the polypeptide chain subject to the constraint that the spatial relationship among the residues of each triplet is fixed by the native-state crystallographic data. The response of each protein to these structural perturbations allows the evolution of each of the four helices in these two proteins to be differentiated. It is found that the two external helices in c‧ unfold before its two internal helices, whereas exactly the opposite behaviour is demonstrated by c-b562 . Each of these cytochromes has an extended, internal, non-helical ('turning') region that initially lags behind the most labile helix but then, at a certain stage (identified for each cytochrome), unravels before any of the four helices present in the native structure. It is believed that these predictions will be useful in guiding future experimental studies on the unfolding of these two cytochromes.

Linking 1D Transition-Metal Coordination Polymers and Different Inorganic Boron Oxides To Construct a Series of 3D Inorganic-Organic Hybrid Borates.

PubMed

Zhi, Shao-Chen; Wang, Yue-Lin; Sun, Li; Cheng, Jian-Wen; Yang, Guo-Yu

2018-02-05

Three inorganic-organic hybrid borates, M(1,4-dab)[B 5 O 7 (OH) 3 ] [M = Zn (1), Cd (2), 1,4-dab = 1,4-diaminobutane)] and Co(1,3-dap)[B 4 O 7 ] (3, 1,3-dap = 1,3-diaminopropane), which integrated characteristics of 1D coordination polymers and 1D/3D inorganic boron oxides have been obtained under solvothermal conditions. Compounds 1 and 2 are isostructural and crystallize in a centrosymmetric space group P2 1 /c; the 3D achiral structures of 1 and 2 consist of the nonhelical Zn/Cd-1,4-dap coordination polymers and 1D B-O chains. Compound 3 crystallizes in a chiral space group P4 3 2 1 2; the helical Co-1,3-dap coordination polymer chains are entrained within a 3D B-O network and finally form the chiral framework. Compounds 1-3 represent good examples of using coordination polymers to construct mixed-motif inorganic-organic hybrid borates. Compounds 1 and 2 display blue luminescence when excited with UV light.

The global distribution of magnetic helicity in the solar corona

NASA Astrophysics Data System (ADS)

Yeates, A. R.; Hornig, G.

2016-10-01

By defining an appropriate field line helicity, we apply the powerful concept of magnetic helicity to the problem of global magnetic field evolution in the Sun's corona. As an ideal-magnetohydrodynamic invariant, the field line helicity is a meaningful measure of how magnetic helicity is distributed within the coronal volume. It may be interpreted, for each magnetic field line, as a magnetic flux linking with that field line. Using magneto-frictional simulations, we investigate how field line helicity evolves in the non-potential corona as a result of shearing by large-scale motions on the solar surface. On open magnetic field lines, the helicity injected by the Sun is largely output to the solar wind, provided that the coronal relaxation is sufficiently fast. But on closed magnetic field lines, helicity is able to build up. We find that the field line helicity is non-uniformly distributed, and is highly concentrated in twisted magnetic flux ropes. Eruption of these flux ropes is shown to lead to sudden bursts of helicity output, in contrast to the steady flux along the open magnetic field lines. Movies are available at http://www.aanda.org

Backbone hydration determines the folding signature of amino acid residues.

PubMed

Bignucolo, Olivier; Leung, Hoi Tik Alvin; Grzesiek, Stephan; Bernèche, Simon

2015-04-08

The relation between the sequence of a protein and its three-dimensional structure remains largely unknown. A lasting dream is to elucidate the side-chain-dependent driving forces that govern the folding process. Different structural data suggest that aromatic amino acids play a particular role in the stabilization of protein structures. To better understand the underlying mechanism, we studied peptides of the sequence EGAAXAASS (X = Gly, Ile, Tyr, Trp) through comparison of molecular dynamics (MD) trajectories and NMR residual dipolar coupling (RDC) measurements. The RDC data for aromatic substitutions provide evidence for a kink in the peptide backbone. Analysis of the MD simulations shows that the formation of internal hydrogen bonds underlying a helical turn is key to reproduce the experimental RDC values. The simulations further reveal that the driving force leading to such helical-turn conformations arises from the lack of hydration of the peptide chain on either side of the bulky aromatic side chain, which can potentially act as a nucleation point initiating the folding process.

Molecular dynamics simulations of theoretical cellulose nanotube models.

PubMed

Uto, Takuya; Kodama, Yuta; Miyata, Tatsuhiko; Yui, Toshifumi

2018-06-15

Nanotubes are remarkable nanoscale architectures for a wide range of potential applications. In the present paper, we report a molecular dynamics (MD) study of the theoretical cellulose nanotube (CelNT) models to evaluate their dynamic behavior in solution (either chloroform or benzene). Based on the one-quarter chain staggering relationship, we constructed six CelNT models by combining the two chain polarities (parallel (P) and antiparallel (AP)) and three symmetry operations (helical right (H R ), helical left (H L ), and rotation (R)) to generate a circular arrangement of molecular chains. Among the four models that retained the tubular form (P-H R , P-H L , P-R, and AP-R), the P-R and AP-R models have the lowest steric energies in benzene and chloroform, respectively. The structural features of the CelNT models were characterized in terms of the hydroxymethyl group conformation and intermolecular hydrogen bonds. Solvent structuring more clearly occurred with benzene than chloroform, suggesting that the CelNT models may disperse in benzene. Copyright © 2018 Elsevier Ltd. All rights reserved.

Lysine hydroxylation of collagen in a fibroblast cell culture system

NASA Technical Reports Server (NTRS)

Uzawa, Katsuhiro; Yeowell, Heather N.; Yamamoto, Kazushi; Mochida, Yoshiyuki; Tanzawa, Hideki; Yamauchi, Mitsuo

2003-01-01

The lysine (Lys) hydroxylation pattern of type I collagen produced by human fibroblasts in culture was analyzed and compared. Fibroblasts were cultured from normal human skin (NSF), keloid (KDF), fetal skin (FDF), and skin tissues of Ehlers-Danlos syndrome type VIA and VIB patients (EDS-VIA and -VIB). The type I collagen alpha chains with or without non-helical telopeptides were purified from the insoluble matrix and analyzed. In comparison with NSFs, KDF and FDF showed significantly higher Lys hydroxylation, particularly in the telopeptide domains of both alpha chains. Both EDS-VIA and -VIB showed markedly lower Lys hydroxylation in the helical domains of both alpha chains whereas that in the telopeptides was comparable with those of NSFs. A similar profile was observed in the tissue sample of the EDS-VIB patient. These results demonstrate that the Lys hydroxylation pattern is domain-specific within the collagen molecule and that this method is useful to characterize the cell phenotypes in normal/pathological connective tissues.

Strong-coupling phases of the spin-orbit-coupled spin-1 Bose-Hubbard chain: Odd-integer Mott lobes and helical magnetic phases

NASA Astrophysics Data System (ADS)

Pixley, J. H.; Cole, William S.; Spielman, I. B.; Rizzi, Matteo; Das Sarma, S.

2017-10-01

We study the odd-integer filled Mott phases of a spin-1 Bose-Hubbard chain and determine their fate in the presence of a Raman induced spin-orbit coupling which has been achieved in ultracold atomic gases; this system is described by a quantum spin-1 chain with a spiral magnetic field. The spiral magnetic field initially induces helical order with either ferromagnetic or dimer order parameters, giving rise to a spiral paramagnet at large field. The spiral ferromagnet-to-paramagnet phase transition is in a universality class with critical exponents associated with the divergence of the correlation length ν ≈2 /3 and the order-parameter susceptibility γ ≈1 /2 . We solve the effective spin model exactly using the density-matrix renormalization group, and compare with both a large-S classical solution and a phenomenological Landau theory. We discuss how these exotic bosonic magnetic phases can be produced and probed in ultracold atomic experiments in optical lattices.

Arginine side chain stacking with peptide plane stabilizes the protein helix conformation in a cooperative way.

PubMed

Wang, Jia; Chen, Jingfei; Li, Jingwen; An, Liaoyuan; Wang, Yefei; Huang, Qingshan; Yao, Lishan

2018-06-01

A combined experimental and computational study is performed for arginine side chain stacking with the protein α-helix. Theremostability measurements of Aristaless homeodomain, a helical protein, suggest that mutating the arginine residue R106, R137 or R141, which has the guanidino side chain stacking with the peptide plane, to alanine, destabilizes the protein. The R-PP stacking has an energy of ∼0.2-0.4 kcal/mol. This stacking interaction mainly comes from dispersion and electrostatics, based on MP2 calculations with the energy decomposition analysis. The calculations also suggest that the stacking stabilizes 2 backbone-backbone h-bonds (i→i-4 and i-3→i-7) in a cooperative way. Desolvation and electrostatic polarization are responsible for cooperativity with the i→i-4 and i-3→i-7 h-bonds, respectively. This cooperativity is supported by a protein α-helices h-bond survey in the pdb databank where stacking shortens the corresponding h-bond distances. © 2018 Wiley Periodicals, Inc.

Self-assembled chiral helical nanofibers by amphiphilic dipeptide derived from d- or l-threonine and application as a template for the synthesis of Au and Ag nanoparticles.

PubMed

Zhang, Han; Xin, Xia; Sun, Jichao; Zhao, Liupeng; Shen, Jinglin; Song, Zhaohua; Yuan, Shiling

2016-12-15

The discovery of a class of self-assembling peptides that spontaneously undergo self-organization into well-ordered structures opened a new avenue for molecular fabrication of biological materials. In this paper, the structure controlled helical nanofibers were prepared by two artificial β-sheet dipeptides with long alkyl chains derived from l- and d-threonine (Thr) and sodium hydroxide (NaOH). These helical nanofibers have been characterized using transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopy, and X-ray powder diffraction (XRD). It was demonstrated that the helicity of the nanofibers could be easily controlled by changing the chirality of the constituent amino acids in the peptide species (d- or l-threonine). Moreover, the hydrogen bonding interactions between the amide groups as well as the hydrophobic interactions among the alkyl chains play important roles in the self-assembly process. It also can be observed that with the passage of time, the hydrogen bonding interactions between the individual nanofiber induced the conversion from nanofibers to nanobelts. Particularly, gold and silver nanoparticles performed good catalytic ability were synthesized using the assembled nanofibers as template. Copyright © 2016 Elsevier Inc. All rights reserved.

Microsecond kinetics in model single- and double-stranded amylose polymers.

PubMed

Sattelle, Benedict M; Almond, Andrew

2014-05-07

Amylose, a component of starch with increasing biotechnological significance, is a linear glucose polysaccharide that self-organizes into single- and double-helical assemblies. Starch granule packing, gelation and inclusion-complex formation result from finely balanced macromolecular kinetics that have eluded precise experimental quantification. Here, graphics processing unit (GPU) accelerated multi-microsecond aqueous simulations are employed to explore conformational kinetics in model single- and double-stranded amylose. The all-atom dynamics concur with prior X-ray and NMR data while surprising and previously overlooked microsecond helix-coil, glycosidic linkage and pyranose ring exchange are hypothesized. In a dodecasaccharide, single-helical collapse was correlated with linkages and rings transitioning from their expected syn and (4)C1 chair conformers. The associated microsecond exchange rates were dependent on proximity to the termini and chain length (comparing hexa- and trisaccharides), while kinetic features of dodecasaccharide linkage and ring flexing are proposed to be a good model for polymers. Similar length double-helices were stable on microsecond timescales but the parallel configuration was sturdier than the antiparallel equivalent. In both, tertiary organization restricted local chain dynamics, implying that simulations of single amylose strands cannot be extrapolated to dimers. Unbiased multi-microsecond simulations of amylose are proposed as a valuable route to probing macromolecular kinetics in water, assessing the impact of chemical modifications on helical stability and accelerating the development of new biotechnologies.

Thermodynamic confinement and alpha-helix persistence length in poly(gamma-benzyl-L-glutamate)-b-poly(dimethyl siloxane)-b-poly(gamma-benzyl-L-glutamate) triblock copolymers.

PubMed

Papadopoulos, P; Floudas, G; Schnell, I; Lieberwirth, I; Nguyen, T Q; Klok, H-A

2006-02-01

The structure and the associated dynamics of a series of poly(gamma-benzyl-L-glutamate)-b-poly(dimethyl siloxane)-b-poly(gamma-benzyl-L-glutamate) (PBLG-b-PDMS-b-PBLG) triblock copolymers were investigated using small- and wide-angle X-ray scattering, NMR, transmission electron microscopy, and dielectric spectroscopy, respectively. The structural analysis revealed phase separation in the case of the longer blocks with defected alpha-helical segments embedded within the block copolymer nanodomains. The alpha-helical persistence length was found to depend on the degree of segregation; thermodynamic confinement and chain stretching results in the partial annihilation of helical defects.

NMR structure of the bovine prion protein

PubMed Central

López García, Francisco; Zahn, Ralph; Riek, Roland; Wüthrich, Kurt

2000-01-01

The NMR structures of the recombinant 217-residue polypeptide chain of the mature bovine prion protein, bPrP(23–230), and a C-terminal fragment, bPrP(121–230), include a globular domain extending from residue 125 to residue 227, a short flexible chain end of residues 228–230, and an N-terminal flexibly disordered “tail” comprising 108 residues for the intact protein and 4 residues for bPrP(121–230), respectively. The globular domain contains three α-helices comprising the residues 144–154, 173–194, and 200–226, and a short antiparallel β-sheet comprising the residues 128–131 and 161–164. The best-defined parts of the globular domain are the central portions of the helices 2 and 3, which are linked by the only disulfide bond in bPrP. Significantly increased disorder and mobility is observed for helix 1, the loop 166–172 leading from the β-strand 2 to helix 2, the end of helix 2 and the following loop, and the last turn of helix 3. Although there are characteristic local differences relative to the conformations of the murine and Syrian hamster prion proteins, the bPrP structure is essentially identical to that of the human prion protein. On the other hand, there are differences between bovine and human PrP in the surface distribution of electrostatic charges, which then appears to be the principal structural feature of the “healthy” PrP form that might affect the stringency of the species barrier for transmission of prion diseases between humans and cattle. PMID:10899999

Molecular analogs of the hemihelix: A computational study of chain molecules containing left- and right-handed helices

NASA Astrophysics Data System (ADS)

Pichierri, Fabio

2014-08-01

Using density functional theory (DFT) we design two novel chain molecules containing a left-handed (thia)helicene unit connected to a right-handed (thia)helicene unit via a phosphoroussbnd phosphorous (Psbnd P) bond. These chains represent the molecular analogs of the novel hemihelix structure recently discovered by a group of Harvard University scientists. The HOMO and LUMO levels of the heterochiral chains, termed hemihelicenes, are localized on the left- and right-handed blocks, respectively. In contrast, the frontier orbitals of the chains containing homochiral (thia)helicenes connected by a Psbnd P bond are delocalized all over the chain.

Edge effects control helical wrapping of carbon nanotubes by polysaccharides

NASA Astrophysics Data System (ADS)

Liu, Yingzhe; Chipot, Christophe; Shao, Xueguang; Cai, Wensheng

2012-03-01

Carbon nanotubes (CNTs) wrapped by polysaccharide chains via noncovalent interactions have been shown to be soluble and dispersed in aqueous environments, and have several potential chemical and biomedical applications. The wrapping mechanism, in particular the role played by the end of the CNT, remains, however, unknown. In this work, a hybrid complex formed by an amylose (AMYL) chain and a single-walled carbon nanotube (SWNT) has been examined by means of atomistic molecular dynamics (MD) simulations to assess its propensity toward self-assembly, alongside its structural characteristics in water. To explore edge effects, the middle and end regions of the SWNT have been chosen as two initial wrapping sites, to which two relative orientations have been assigned, i.e. parallel and orthogonal. The present results prove that AMYL can wrap spontaneously around the tubular surface, starting from the end of the SWNT and driven by both favorable van der Waals attraction and hydrophobic interactions, and resulting in a perfectly compact, helical conformation stabilized by an interlaced hydrogen-bond network. Principal component analysis carried out over the MD trajectories reveals that stepwise burial of hydrophobic faces of pyranose rings controlled by hydrophobic interactions is a key step in the formation of the helix. Conversely, if wrapping proceeds from the middle of the SWNT, self-organization into a helical structure is not observed due to strong van der Waals attractions preventing the hydrophobic faces of the AMYL chain generating enough contacts with the tubular surface.Carbon nanotubes (CNTs) wrapped by polysaccharide chains via noncovalent interactions have been shown to be soluble and dispersed in aqueous environments, and have several potential chemical and biomedical applications. The wrapping mechanism, in particular the role played by the end of the CNT, remains, however, unknown. In this work, a hybrid complex formed by an amylose (AMYL) chain and a single-walled carbon nanotube (SWNT) has been examined by means of atomistic molecular dynamics (MD) simulations to assess its propensity toward self-assembly, alongside its structural characteristics in water. To explore edge effects, the middle and end regions of the SWNT have been chosen as two initial wrapping sites, to which two relative orientations have been assigned, i.e. parallel and orthogonal. The present results prove that AMYL can wrap spontaneously around the tubular surface, starting from the end of the SWNT and driven by both favorable van der Waals attraction and hydrophobic interactions, and resulting in a perfectly compact, helical conformation stabilized by an interlaced hydrogen-bond network. Principal component analysis carried out over the MD trajectories reveals that stepwise burial of hydrophobic faces of pyranose rings controlled by hydrophobic interactions is a key step in the formation of the helix. Conversely, if wrapping proceeds from the middle of the SWNT, self-organization into a helical structure is not observed due to strong van der Waals attractions preventing the hydrophobic faces of the AMYL chain generating enough contacts with the tubular surface. Electronic supplementary information (ESI) available: Table S1 shows the details of the systems for molecular dynamics simulations. Figure S1 shows time evolution of the distance RMSD over the heavy atoms of the AMYL chain with respect to the initial structure. The hydrogen-bond network including inter-residue and inter-turn hydrogen bonds monitored in the course of self-assembly is delineated in Figure S2. Figure S3 shows the equilibrium conformation of the initial right-handed AMYL chain wrapping the nanotube. See DOI: 10.1039/c2nr11979j

Photoinduced electron transfer through peptide-based self-assembled monolayers chemisorbed on gold electrodes: directing the flow-in and flow-out of electrons through peptide helices.

PubMed

Venanzi, Mariano; Gatto, Emanuela; Caruso, Mario; Porchetta, Alessandro; Formaggio, Fernando; Toniolo, Claudio

2014-08-21

Photoinduced electron transfer (PET) experiments have been carried out on peptide self-assembled monolayers (SAM) chemisorbed on a gold substrate. The oligopeptide building block was exclusively formed by C(α)-tetrasubstituted α-aminoisobutyric residues to attain a helical conformation despite the shortness of the peptide chain. Furthermore, it was functionalized at the C-terminus by a pyrene choromophore to enhance the UV photon capture cross-section of the compound and by a lipoic group at the N-terminus for linking to gold substrates. Electron transfer across the peptide SAM has been studied by photocurrent generation experiments in an electrochemical cell employing a gold substrate modified by chemisorption of a peptide SAM as a working electrode and by steady-state and time-resolved fluorescence experiments in solution and on a gold-coated glass. The results show that the electronic flow through the peptide bridge is strongly asymmetric; i.e., PET from the C-terminus to gold is highly favored with respect to PET in the opposite direction. This effect arises from the polarity of the Au-S linkage (Au(δ+)-S(δ-), junction effect) and from the electrostatic field generated by the peptide helix.

Smoke-derived karrikin perception by the α/β-hydrolase KAI2 from Arabidopsis

PubMed Central

Guo, Yongxia; Zheng, Zuyu; La Clair, James J.; Chory, Joanne; Noel, Joseph P.

2013-01-01

Genetic studies in Arabidopsis implicate an α/β-hydrolase, KARRIKIN-INSENSITIVE 2 (KAI2) as a receptor for karrikins, germination-promoting butenolide small molecules found in the smoke of burned plants. However, direct biochemical evidence for the interaction between KAI2 and karrikin and for the mechanism of downstream signaling by a KAI2–karrikin complex remain elusive. We report crystallographic analyses and ligand-binding experiments for KAI2 recognition of karrikins. The karrikin-1 (KAR1) ligand sits in the opening to the active site abutting a helical domain insert but distal from the canonical catalytic triad (Ser95-His246-Asp217) of α/β-hydrolases, consistent with the lack of detectable hydrolytic activity by purified KAI2. The closest approach of KAR1 to Ser95-His246-Asp217 is 3.8 Å from His246. Six aromatic side chains, including His246, encapsulate KAR1 through geometrically defined aromatic–aromatic interactions. KAR1 binding induces a conformational change in KAI2 at the active site entrance. A crevice of hydrophobic residues linking the polar edge of KAR1 and the helical domain insert suggests that KAI2–KAR1 creates a contiguous interface for binding signaling partners in a ligand-dependent manner. PMID:23613584

Smoke-derived karrikin perception by the α/β-hydrolase KAI2 from Arabidopsis.

PubMed

Guo, Yongxia; Zheng, Zuyu; La Clair, James J; Chory, Joanne; Noel, Joseph P

2013-05-14

Genetic studies in Arabidopsis implicate an α/β-hydrolase, KARRIKIN-INSENSITIVE 2 (KAI2) as a receptor for karrikins, germination-promoting butenolide small molecules found in the smoke of burned plants. However, direct biochemical evidence for the interaction between KAI2 and karrikin and for the mechanism of downstream signaling by a KAI2-karrikin complex remain elusive. We report crystallographic analyses and ligand-binding experiments for KAI2 recognition of karrikins. The karrikin-1 (KAR1) ligand sits in the opening to the active site abutting a helical domain insert but distal from the canonical catalytic triad (Ser95-His246-Asp217) of α/β-hydrolases, consistent with the lack of detectable hydrolytic activity by purified KAI2. The closest approach of KAR1 to Ser95-His246-Asp217 is 3.8 Å from His246. Six aromatic side chains, including His246, encapsulate KAR1 through geometrically defined aromatic-aromatic interactions. KAR1 binding induces a conformational change in KAI2 at the active site entrance. A crevice of hydrophobic residues linking the polar edge of KAR1 and the helical domain insert suggests that KAI2-KAR1 creates a contiguous interface for binding signaling partners in a ligand-dependent manner.

Molecular dynamics of individual alpha-helices of bacteriorhodopsin in dimyristol phosphatidylocholine. I. Structure and dynamics.

PubMed

Woolf, T B

1997-11-01

Understanding the role of the lipid bilayer in membrane protein structure and dynamics is needed for tertiary structure determination methods. However, the molecular details are not well understood. Molecular dynamics computer calculations can provide insight into these molecular details of protein:lipid interactions. This paper reports on 10 simulations of individual alpha-helices in explicit lipid bilayers. The 10 helices were selected from the bacteriorhodopsin structure as representative alpha-helical membrane folding components. The bilayer is constructed of dimyristoyl phosphatidylcholine molecules. The only major difference between simulations is the primary sequence of the alpha-helix. The results show dramatic differences in motional behavior between alpha-helices. For example, helix A has much smaller root-mean-squared deviations than does helix D. This can be understood in terms of the presence of aromatic residues at the interface for helix A that are not present in helix D. Additional motions are possible for the helices that contain proline side chains relative to other amino acids. The results thus provide insight into the types of motion and the average structures possible for helices within the bilayer setting and demonstrate the strength of molecular simulations in providing molecular details that are not directly visualized in experiments.

Spectroscopic studies of bacteriorhodopsin fragments dissolved in organic solution.

PubMed Central

Torres, J; Padrós, E

1995-01-01

Fourier transform infrared and UV fourth-derivative spectroscopies were used to study the secondary structure of bacteriorhodopsin and its chymotryptic and one of the sodium borohydride fragments dissolved in chloroform-methanol (1:1, v/v), 0.1 M LiClO4. The C1 fragment (helices C, D, E, F, and G) showed an alpha-helical content of about 53%, whereas C2 (helices A and B) had about 60%, and B2 (helices F and G) about 65% alpha-helix. The infrared main band indicated differences in alpha-helical properties between these fragments. These techniques were also used to obtain information on the interactions among helices. According to the results obtained from the hydrogen/deuterium exchange kinetics, about 40% of the amide protons of C2 are particularly protected against exchange, whereas for the C1 fragment this process is unexpectedly fast. UV fourth-derivative spectra of these samples were used to obtain information about the environment of Trp side chains. The results showed that the Trp residues of C2 are more shielded from the solvent than those of C1 or B2. The results of this work indicate that the specific interactions existing between the transmembrane segments induce different types of helical conformations in native bacteriorhodopsin. PMID:7612847

Cooperative polymerization of α-helices induced by macromolecular architecture

NASA Astrophysics Data System (ADS)

Baumgartner, Ryan; Fu, Hailin; Song, Ziyuan; Lin, Yao; Cheng, Jianjun

2017-07-01

Catalysis observed in enzymatic processes and protein polymerizations often relies on the use of supramolecular interactions and the organization of functional elements in order to gain control over the spatial and temporal elements of fundamental cellular processes. Harnessing these cooperative interactions to catalyse reactions in synthetic systems, however, remains challenging due to the difficulty in creating structurally controlled macromolecules. Here, we report a polypeptide-based macromolecule with spatially organized α-helices that can catalyse its own formation. The system consists of a linear polymeric scaffold containing a high density of initiating groups from which polypeptides are grown, forming a brush polymer. The folding of polypeptide side chains into α-helices dramatically enhances the polymerization rate due to cooperative interactions of macrodipoles between neighbouring α-helices. The parameters that affect the rate are elucidated by a two-stage kinetic model using principles from nucleation-controlled protein polymerizations; the key difference being the irreversible nature of this polymerization.

Subunit composition and structure of subcomponent C1q of the first component of human complement.

PubMed

Reid, K B; Porter, R R

1976-04-01

1. Unreduced human subcomponent C1q was shown by electrophoresis on polyacrylamide gels run in the presence of sodium dodecyl sulphate to be composed of two types of non-covalently linked subunits of apparent mol.wts. 69 000 and 54 000. The ratio of the two subunits was markedly affected by the ionic strength of the applied sample. At a low ionic strength of applied sample, which gave the optimum value for the 54 000-apparent mol.wt. subunit, a ratio of 1.99:1.00 was obtained for the ratio of the 69 000-apparent mol.wt. subunit to the 5400-apparent-mol.wt. subunit. The amount of the 54 000-apparent-mol.wt. subunit detected in the expected position on the gel was found to be inversely proportional to increases in the ionic strength of the applled sample. 2. Human subcomponent C1q on reduction and alkylation, or oxidation, yields equimolar amounts of three chains designated A, B and C [Reid et al. (1972) Biochem. J. 130, 749-763]. The results obtained by Yonemasu & Stroud [(1972) Immunochemistry 9, 545-554], which showed that the 69 000-apparent-mol.wt. subunit was a disulphide-linked dimer of the A and B chains and that the 54 000-apparent-mol.wt. subunit was a disulphide-linked dimer of the C chain, were confirmed. 3. Gel filtration on Sephadex G-200 in 6.0M-guanidinium chloride showed that both types of unreduced subunit were eluted together as a single symmetrical peak of apparent mol.wt. 49 000-50 000 when globular proteins were used as markers. The molecular weights of the oxidized or reduced A, B and C chains have been shown previously to be very similar all being in the range 23 000-24 000 [Reid et al. (1972) Biochem. J. 130, 749-763; Reid (1974) Biochem. J. 141, 189-203]. 4. It is proposed that subcomponent C1q (mol.wt. 410000) is composed of nine non-covalently linked subunits, i.e. six A-B dimers and three C-C dimers. 5. A structure for subcomponent C1q is proposed and is based on the assumption that the collagen-like regions of 78 residues in each of the A, B and C chains are combined to form a triple-helical structure of the same type as is found in collagens.

Four unexpected lanthanide coordination polymers involving in situ reaction of solvent N, N-Dimethylformamide

NASA Astrophysics Data System (ADS)

Jin, Jun-Cheng; Tong, Wen-Quan; Fu, Ai-Yun; Xie, Cheng-Gen; Chang, Wen-Gui; Wu, Ju; Xu, Guang-Nian; Zhang, Ya-Nan; Li, Jun; Li, Yong; Yang, Peng-Qi

2015-05-01

Four unexpected 2D lanthanide coordination polymers have been synthesized through in situ reactions of DMF solvent under solvothermal conditions. The isostructural complexes 1-3 contain four types of 21 helical chains. While the Nd(III) ions are bridged through μ2-HIDC2- and oxalate to form a 2D sheet along the bc plane without helical character in 4. Therefore, complex 1 exhibits bright red solid-state phosphorescence upon exposure to UV radiation at room temperature.

Conformational properties of two exopolysaccharides produced by Inquilinus limosus, a cystic fibrosis lung pathogen.

PubMed

Kuttel, Michelle; Ravenscroft, Neil; Foschiatti, Michela; Cescutti, Paola; Rizzo, Roberto

2012-03-01

Inquilinus limosus is a multi-resistant bacterium found in the respiratory tract of patients with cystic fibrosis. This bacterium produces two unique fully pyruvylated exopolysaccharides in similar quantities: an α-(1→2)-linked mannan and a β-(1→3)-linked glucan. We employed molecular modelling methods to probe the characteristic conformations and dynamics of these polysaccharides, with corroboration from potentiometric titrations and circular dichroism experiments. Our calculations reveal different structural motifs for the mannan and glucan polysaccharides: the glucan forms primarily right-handed helices with a wide range of extensions, while the mannan forms only left-handed helices. This finding is supported by our circular dichroism experiments. Our calculations also show that the (1→3)-β-d-Glcp linkage is more dynamically flexible than the (1→2)-α-d-Manp: the glucan characteristically forms a range of wide helices with large central cavities. In contrast, the mannan forms rigid regular 'bottlebrush' helices with a minimal central cavity. The widely different character of these two polymers suggests a possible differentiation of biological roles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Flaws in foldamers: conformational uniformity and signal decay in achiral helical peptide oligomers† †Electronic supplementary information (ESI) available: Synthesis and characterisation of all new compounds. See DOI: 10.1039/c4sc03944k Click here for additional data file.

PubMed Central

Le Bailly, Bryden A. F.; Byrne, Liam; Diemer, Vincent; Foroozandeh, Mohammadali; Morris, Gareth A.

2015-01-01

Although foldamers, by definition, are extended molecular structures with a well-defined conformation, minor conformers must be populated at least to some extent in solution. We present a quantitative analysis of these minor conformers for a series of helical oligomers built from achiral but helicogenic α-amino acids. By measuring the chain length dependence or chain position dependence of NMR or CD quantities that measure screw-sense preference in a helical oligomer, we quantify values for the decay constant of a conformational signal as it passes through the molecular structure. This conformational signal is a perturbation of the racemic mixture of M and P helices that such oligomers typically adopt by the inclusion of an N or C terminal chiral inducer. We show that decay constants may be very low (<1% signal loss per residue) in non-polar solvents, and we evaluate the increase in decay constant that results in polar solvents, at higher temperatures, and with more conformationally flexible residues such as Gly. Decay constants are independent of whether the signal originates from the N or the C terminus. By interpreting the decay constant in terms of the probability with which conformations containing a screw-sense reversal are populated, we quantify the populations of these alternative minor conformers within the overall ensemble of secondary structures adopted by the foldamer. We deduce helical persistence lengths for Aib polymers that allow us to show that in a non-polar solvent a peptide helix, even in the absence of chiral residues, may continue with the same screw sense for approximately 200 residues. PMID:29308146

Hydrothermal synthesis, crystal structure and properties of 2-D and 3-D lanthanide sulfates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Yan; Ding Shaohua; Zheng Xuefang

2007-07-15

Two new lanthanum sulfates DySO{sub 4}(OH) 1 and Eu{sub 2}(SO{sub 4}){sub 3}(H{sub 2}O){sub 8} 2 have been hydrothermally synthesized. The colorless crystals were characterized by IR, TGA, ICP and XRD. The structure was determined by single-crystal X-ray diffraction. 1 crystallizes with monoclinic symmetry, space group P2(1)/n [a=7.995(4) A, b=10.945(5) A, c=8.164(4) A, {alpha}=90{sup o}, {beta}=93.619(6){sup o}, {gamma}=90{sup o}, V=713.0(5) A{sup 3}, Z=8]. It displays a three-dimensional framework, based on the novel Dy-O chains connected by the sulfate groups through helical chains. 2 crystallizes with monoclinic symmetry, space group C2/c, [a=13.5605(17) A, b=6.7676(8) A, c=18.318(2) A, {alpha}=90{sup o}, {beta}=102.265(2){sup o}, {gamma}=90{supmore » o}, V=1642.7 (4) A{sup 3}, Z=4]. Its layered framework is attained by the europium atoms connected by the sulfate groups arranged in a helical manner. - Graphical abstract: Two new lanthanum sulfates DySO{sub 4}(OH) 1 and Eu{sub 2} (SO{sub 4}){sub 3} (H{sub 2}O){sub 8} 2 have been hydrothermally synthesized. The colorless crystals were characterized by IR, TGA, ICP and XRD. The structure was determined by single-crystal X-ray diffraction. It displays a three dimensional framework, based on the novel Dy-O chains connected by the sulfate groups through helical chains.« less

Synthesis and characterization of poly-L-leucine initialized and immobilized by rehydrated hydrotalcite: understanding stability and the nature of interaction.

PubMed

Miranda, Ronald-Alexander; Finocchio, Elisabetta; Llorca, Jordi; Medina, Francisco; Ramis, Gianguido; Sueiras, Jesús E; Segarra, Anna M

2013-10-07

PLLs were synthesized by the ring-opening polycondensation (ROP) method using α-L-leucine N-carboxyanhydride (NCA) and initialized by triethylamine (Et3N), water or rehydrated hydrotalcite (HTrus). The role of temperature, different initiators and water in ROP was further investigated. In general, the initiators used in the polymerization reaction lead to PLL alpha-helical chains containing 5-40 monomers with NCA endgroups via a monomer-activated mechanism. However, the water has a twofold effect on ROP, as both a nucleophile and a base, which involves competition between two different types of initiating mechanisms (nucleophilic attack or deprotonation of the NCA monomer) in the polymerization reaction. This competition provides as a main product NCA endgroups with an alpha-helical structure and leads to the formation of the PLL cyclic-chains and beta-sheet structures which reduce the polymer Mw and the PD of the polypeptide. Furthermore, the water can hydrolyze the NCA endgroups resulting in PLL alpha-helical chains that contain living groups as the main product. On the other hand, the HTrus presents a double role: as both an initiator and a support. The polymers synthesized in the presence of HTrus presented a HT-carboxylate endgroup. The PLLs immobilized in HTrus through an anion-exchange method performed for just 30 minutes presented the PLL immobilized in the interlayer space of the HTrus. The PLL chains of the immobilized counterpart are stabilized by H-bonding with the M-OH of the HT structure. All the polypeptides and biohybrid materials synthesized have been characterized using different techniques (EA, ICP, XRD, Raman, MALDI-TOF, ESI-TOF, FT-IR at increasing temperatures, TG/DT analyses and TEM).

Mercury coordination polymers with flexible ethane-1,2-diyl-bis-(pyridyl-3-carboxylate): Synthesis, structures, thermal and luminescent properties

NASA Astrophysics Data System (ADS)

Vallejos, Javier; Brito, Iván; Cárdenas, Alejandro; Llanos, Jaime; Bolte, Michael; López-Rodríguez, Matías

2015-03-01

The reaction of the flexible ligand, ethane-1,2-diyl-bis-(pyridyl-3-carboxylate), (L) with HgI2 and HgBr2 salts under the same experimental conditions leads to the formation of two coordination polymers with different motifs: {[Hg(L)(Br2)]}n(1) and {[Hg(L)(I2)]}n(2). In both compounds, the ligand, (L) acts in a μ2-N:N‧-bidentate fashion to link HgBr2 and HgI2 units to form a linear and helical chain motif, along [1 0 0] for (1) and [0 0 1] for (2). The ethylene moiety of (L) has gauche and trans conformation in compounds (1) and (2), respectively. The flexible conformation of L produces differences in the optical and crystal properties of the two compounds.

Moreau's hydrodynamic helicity and the life of vortex knots and links

NASA Astrophysics Data System (ADS)

Irvine, William T. M.

2018-03-01

This contribution to an issue of Comptes rendus Mécanique, commemorating the scientific work of Jean-Jacques Moreau (1923-2014), is intended to give a brief overview of recent developments in the study of helicity dynamics in real fluids and an outlook on the growing legacy of Moreau's work. Moreau's discovery of the conservation of hydrodynamic helicity, presented in an article in the Comptes rendus de l'Académie des sciences in 1961, was not recognized until long after it was published. This seminal contribution is gaining a new life now that modern developments allow the study of helicity and topology in fields and is having a growing impact on diverse areas of physics.

How Rosalind Franklin Discovered the Helical Structure of DNA: Experiments in Diffraction

NASA Astrophysics Data System (ADS)

Braun, Gregory; Tierney, Dennis; Schmitzer, Heidrun

2011-03-01

Rosalind Franklin, a chemical physicist (1920-1958), used x-ray diffraction to determine the structure of DNA. What exactly could she read out from her x-ray pattern, shown in Fig. 1? In lecture notes dated November 1951, R. Franklin wrote the following: "The results suggest a helical structure (which must be very closely packed) containing 2, 3 or 4 co-axial nucleic acid chains per helical unit, and having the phosphate groups near the outside."2 This was 16 months before J. D. Watson and F. Crick published their description of DNA, which was based on R. Franklin's x-ray photos. How they gained access to her x-ray photos is a fascinating tale of clashing personalities and male chauvinism.2,3

Ultrafast hydrogen exchange reveals specific structural events during the initial stages of folding of cytochrome c.

PubMed

Fazelinia, Hossein; Xu, Ming; Cheng, Hong; Roder, Heinrich

2014-01-15

Many proteins undergo a sharp decrease in chain dimensions during early stages of folding, prior to the rate-limiting step in folding. However, it remains unclear whether compact states are the result of specific folding events or a general hydrophobic collapse of the poly peptide chain driven by the change in solvent conditions. To address this fundamental question, we extended the temporal resolution of NMR-detected H/D exchange labeling experiments into the microsecond regime by adopting a microfluidics approach. By observing the competition between H/D exchange and folding as a function of labeling pH, coupled with direct measurement of exchange rates in the unfolded state, we were able to monitor hydrogen-bond formation for over 50 individual backbone NH groups within the initial 140 microseconds of folding of horse cytochrome c. Clusters of solvent-shielded amide protons were observed in two α-helical segments in the C-terminal half of the protein, while the N-terminal helix remained largely unstructured, suggesting that proximity in the primary structure is a major factor in promoting helix formation and association at early stages of folding, while the entropically more costly long-range contacts between the N- and C-terminal helices are established only during later stages. Our findings clearly indicate that the initial chain condensation in cytochrome c is driven by specific interactions among a subset of α-helical segments rather than a general hydrophobic collapse.

Helical structures in vertically aligned dust particle chains in a complex plasma

NASA Astrophysics Data System (ADS)

Hyde, Truell W.; Kong, Jie; Matthews, Lorin S.

2013-05-01

Self-assembly of structures from vertically aligned, charged dust particle bundles within a glass box placed on the lower, powered electrode of a Gaseous Electronics Conference rf reference cell were produced and examined experimentally. Self-organized formation of one-dimensional vertical chains, two-dimensional zigzag structures, and three-dimensional helical structures of triangular, quadrangular, pentagonal, hexagonal, and heptagonal symmetries are shown to occur. System evolution is shown to progress from a one-dimensional chain structure, through a zigzag transition to a two-dimensional, spindlelike structure, and then to various three-dimensional, helical structures exhibiting multiple symmetries. Stable configurations are found to be dependent upon the system confinement, γ2=ω0h/ω0v2 (where ω0h,v are the horizontal and vertical dust resonance frequencies), the total number of particles within a bundle, and the rf power. For clusters having fixed numbers of particles, the rf power at which structural phase transitions occur is repeatable and exhibits no observable hysteresis. The critical conditions for these structural phase transitions as well as the basic symmetry exhibited by the one-, two-, and three-dimensional structures that subsequently develop are in good agreement with the theoretically predicted configurations of minimum energy determined employing molecular dynamics simulations for charged dust particles confined in a prolate, spheroidal potential as presented theoretically by Kamimura and Ishihara [Kamimura and Ishihara, Phys. Rev. EPLEEE81063-651X10.1103/PhysRevE.85.016406 85, 016406 (2012)].

Impact of helical organization on the photovoltaic properties of oligothiophene supramolecular polymers† †Electronic supplementary information (ESI) available: Synthesis and characterization of 3 and 4, UV-vis spectra, solar cell device properties and AFM images. See DOI: 10.1039/c7sc05093c

PubMed Central

Ouchi, Hayato; Kizaki, Takahiro; Yamato, Masaki; Lin, Xu; Hoshi, Nagahiro; Silly, Fabien; Kajitani, Takashi; Fukushima, Takanori

2018-01-01

Helical self-assembly of functional π-conjugated molecules offers unique photochemical and electronic properties in the spectroscopic level, but there are only a few examples that demonstrate their positive impact on the optoelectronic device level. Here, we demonstrate that hydrogen-bonded tapelike supramolecular polymers of a barbiturated oligo(alkylthiophene) show notable improvement in their photovoltaic properties upon organizing into helical nanofibers. A tapelike hydrogen-bonded supramolecular array of barbiturated oligo(butylthiophene) molecules was directly visualized by STM at a liquid–solid interface. TEM, AFM and XRD revealed that the tapelike supramolecular polymers further organize into helical nanofibers in solution and bulk states. Bulk heterojunction solar cells of the helical nanofibers and soluble fullerene showed a power conversion efficiency of 4.5%, which is markedly high compared to that of the regioisomer of butyl chains organizing into 3D lamellar agglomerates. PMID:29780493

Tile-based self-assembly of a triple-helical polysaccharide into cell wall-like mesoporous nanocapsules.

PubMed

Wu, Chaoxi; Wang, Xiaoying; Wang, Jianjing; Zhang, Zhen; Wang, Zhiping; Wang, Yifei; Tang, Shunqing

2017-07-20

Tile-based self-assembly is a robust system in the construction of three-dimensional DNA nanostructures but it has been rarely applied to other helical biopolymers. β-Glucan is an immunoactive natural polymer which exists in a triple helical conformation. Herein, we report that β-glucan, after modification using two types of short chain acyl groups, can self-assemble into tiles with inactivated sticky ends at the interface of two solvents. These tiles consist of a single layer of helices laterally aligned, and the sticky ends can be activated when a few acyl groups at the ends are removed; these tiles can further pack into mesoporous nanocapsules, in a similar process as the sticky DNA tiles pack into complex polyhedral nano-objects. These nanocapsules were found to have targeted effects to antigen presenting cells in a RAW264.7 cell model. Our study suggests that tile-based self-assembly can be a general strategy for helical biopolymers, and on fully exploiting this strategy, various new functional nanostructures will become accessible in the future.

Preparation of intact monomeric collagen from rat tail tendon and skin and the structure of the nonhelical ends in solution.

PubMed

Chandrakasan, G; Torchia, D A; Piez, K A

1976-10-10

Procedures for the preparation of soluble collagen from rat skin and tail tendon were reviewed and revised to permit the preparation of native monomeric collagen with intact nonhelical ends. The degree of intactness was estimated from the tyrosine content, which is present only in the nonhelical ends, and by mobility of the COOH-terminal cyanogen bromide peptide of the alpha1 chain on sodium dodecyl sulfate gels. The amount of covalently cross-linked polymeric material present was estimated by molecular sieve chromatography of denatured samples. Rapid purification in the cold was sufficient to prevent or greatly reduce proteolytic alteration. Fractionation by salt precipitation at acid pH was effective in reducing the content of polymeric material. Rat tail tendon yielded completely intact native collagen, but some high molecular weight aggregates remained. Collagen from the skin of lathyritic rats was easier to obtain free of aggregates, but contained about 1 less tyrosine residue per alpha1 chain even when isolated in the presence of enzyme inhibitors. Proton NMR spectra of denatured acidic solutions of these preparations showed that 4 to 5 tyrosine residues per alpha chain were present, confirming the chemical analysis. Spectra of the native molecule showed that about the same number of tyrosine residues per chain are in rapid motion, unlike residues in the helical portion of the molecule, a result which shows that the nonhelical ends of the native molecule are unstructured in acidic solution.

Peptide design using alpha,beta-dehydro amino acids: from beta-turns to helical hairpins.

PubMed

Mathur, Puniti; Ramakumar, S; Chauhan, V S

2004-01-01

Incorporation of alpha,beta-dehydrophenylalanine (DeltaPhe) residue in peptides induces folded conformations: beta-turns in short peptides and 3(10)-helices in larger ones. A few exceptions-namely, alpha-helix or flat beta-bend ribbon structures-have also been reported in a few cases. The most favorable conformation of DeltaPhe residues are (phi,psi) approximately (-60 degrees, -30 degrees ), (-60 degrees, 150 degrees ), (80 degrees, 0 degrees ) or their enantiomers. DeltaPhe is an achiral and planar residue. These features have been exploited in designing DeltaPhe zippers and helix-turn-helix motifs. DeltaPhe can be incorporated in both right and left-handed helices. In fact, consecutive occurrence of three or more DeltaPhe amino acids induce left-handed screw sense in peptides containing L-amino acids. Weak interactions involving the DeltaPhe residue play an important role in molecular association. The C--H.O==C hydrogen bond between the DeltaPhe side-chain and backbone carboxyl moiety, pi-pi stacking interactions between DeltaPhe side chains belonging to enantiomeric helices have shown to stabilize folding. The unusual capability of a DeltaPhe ring to form the hub of multicentered interactions namely, a donor in aromatic C--H.pi and C--H.O==C and an acceptor in a CH(3).pi interaction suggests its exploitation in introducing long-range interactions in the folding of supersecondary structures. Copyright 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004

Molecular modeling of biomembranes and their complexes with protein transmembrane α-helices

NASA Astrophysics Data System (ADS)

Kuznetsov, Andrey S.; Smirnov, Kirill V.; Antonov, Mikhail Yu.; Nikolaev, Ivan N.; Efremov, Roman G.

2017-11-01

Helical segments are common structural elements of membrane proteins. Dimerization and oligomerization of transmembrane (TM) α-helices provides the framework for spatial structure formation and protein-protein interactions. The membrane itself also takes part in the protein functioning. There are some examples of the mutual influence of the lipid bilayer properties and embedded membrane proteins. This work aims at the detail investigation of protein-lipid interactions using model systems: TM peptides corresponding to native protein segments. Three peptides were considered corresponding to TM domains of human glycophorin A (GpA), epidermal growth factor receptor (EGFR) and proposed TM-segment of human neuraminidase-1 (Neu1). A computational analysis of structural and dynamical properties was performed using molecular dynamics method. Monomers of peptides were considered incorporated into hydrated lipid bilayers. It was confirmed, that all these TM peptides have stable helical conformation in lipid environment, and the mutual adaptation of peptides and membrane was observed. It was shown that incorporation of the peptide into membrane results in the modulation of local and mean structural properties of the bilayer. Each peptide interacts with lipid acyl chains having special binding sites on the surface of central part of α-helix that exist for at least 200 ns. However, lipid acyl chains substitute each other faster occupying the same site. The formation of a special pattern of protein-lipid interactions may modulate the association of TM domains of membrane proteins, so membrane environment should be considered when proposing new substances targeting cell receptors.

Boehringer Mannheim award lecture 1995. La conference Boehringer Mannheim 1995. De novo design of alpha-helical proteins: basic research to medical applications.

PubMed

Hodges, R S

1996-01-01

The two-stranded alpha-helical coiled-coil is a universal dimerization domain used by nature in a diverse group of proteins. The simplicity of the coiled-coil structure makes it an ideal model system to use in understanding the fundamentals of protein folding and stability and in testing the principles of de novo design. The issues that must be addressed in the de novo design of coiled-coils for use in research and medical applications are (i) controlling parallel versus antiparallel orientation of the polypeptide chains, (ii) controlling the number of helical strands in the assembly (iii) maximizing stability of homodimers or heterodimers in the shortest possible chain length that may require the engineering of covalent constraints, and (iv) the ability to have selective heterodimerization without homodimerization, which requires a balancing of selectivity versus affinity of the dimerization strands. Examples of our initial inroads in using this de novo design motif in various applications include: heterodimer technology for the detection and purification of recombinant peptides and proteins; a universal dimerization domain for biosensors; a two-stage targeting and delivery system; and coiled-coils as templates for combinatorial helical libraries for basic research and drug discovery and as synthetic carrier molecules. The universality of this dimerization motif in nature suggests an endless number of possibilities for its use in de novo design, limited only by the creativity of peptide-protein engineers.

Complete primary structure of rainbow trout type I collagen consisting of alpha1(I)alpha2(I)alpha3(I) heterotrimers.

PubMed

Saito, M; Takenouchi, Y; Kunisaki, N; Kimura, S

2001-05-01

The subunit compositions of skin and muscle type I collagens from rainbow trout were found to be alpha1(I)alpha2(I)alpha3(I) and [alpha1(I)](2)alpha2(I), respectively. The occurrence of alpha3(I) has been observed only for bonyfish. The skin collagen exhibited more susceptibility to both heat denaturation and MMP-13 digestion than the muscle counterpart; the former had a lower denaturation temperature by about 0.5 degrees C than the latter. The lower stability of skin collagen, however, is not due to the low levels of imino acids because the contents of Pro and Hyp were almost constant in both collagens. On the other hand, some cDNAs coding for the N-terminal and/or a part of triple-helical domains of proalpha(I) chains were cloned from the cDNA library of rainbow trout fibroblasts. These cDNAs together with the previously cloned collagen cDNAs gave information about the complete primary structure of type I procollagen. The main triple-helical domain of each proalpha(I) chain had 338 uninterrupted Gly-X-Y triplets consisting of 1014 amino acids and was unique in its high content of Gly-Gly doublets. In particular, the bonyfish-specific alpha(I) chain, proalpha3(I) was characterized by the small number of Gly-Pro-Pro triplets, 19, and the large number of Gly-Gly doublets, 38, in the triple-helical domain, compared to 23 and 22, respectively, for proalpha1(I). The small number of Gly-Pro-Pro and the large number of Gly-Gly in proalpha3(I) was assumed to partially loosen the triple-helical structure of skin collagen, leading to the lower stability of skin collagen mentioned above. Finally, phylogenetic analyses revealed that proalpha3(I) had diverged from proalpha1(I). This study is the first report of the complete primary structure of fish type I procollagen.

Flexible helical-axis stellarator

DOEpatents

Harris, Jeffrey H.; Hender, Timothy C.; Carreras, Benjamin A.; Cantrell, Jack L.; Morris, Robert N.

1988-01-01

An 1=1 helical winding which spirals about a conventional planar, circular central conductor of a helical-axis stellarator adds a significant degree of flexibility by making it possible to control the rotational transform profile and shear of the magnetic fields confining the plasma in a helical-axis stellarator. The toroidal central conductor links a plurality of toroidal field coils which are separately disposed to follow a helical path around the central conductor in phase with the helical path of the 1=1 winding. This coil configuration produces bean-shaped magnetic flux surfaces which rotate around the central circular conductor in the same manner as the toroidal field generating coils. The additional 1=1 winding provides flexible control of the magnetic field generated by the central conductor to prevent the formation of low-order resonances in the rotational transform profile which can produce break-up of the equilibrium magnetic surfaces. Further, this additional winding can deepen the magnetic well which together with the flexible control provides increased stability.

Role of single-point mutations and deletions on transition temperatures in ideal proteinogenic heteropolymer chains in the gas phase.

PubMed

Olivares-Quiroz, L

2016-07-01

A coarse-grained statistical mechanics-based model for ideal heteropolymer proteinogenic chains of non-interacting residues is presented in terms of the size K of the chain and the set of helical propensities [Formula: see text] associated with each residue j along the chain. For this model, we provide an algorithm to compute the degeneracy tensor [Formula: see text] associated with energy level [Formula: see text] where [Formula: see text] is the number of residues with a native contact in a given conformation. From these results, we calculate the equilibrium partition function [Formula: see text] and characteristic temperature [Formula: see text] at which a transition from a low to a high entropy states is observed. The formalism is applied to analyze the effect on characteristic temperatures [Formula: see text] of single-point mutations and deletions of specific amino acids [Formula: see text] along the chain. Two probe systems are considered. First, we address the case of a random heteropolymer of size K and given helical propensities [Formula: see text] on a conformational phase space. Second, we focus our attention to a particular set of neuropentapeptides, [Met-5] and [Leu-5] enkephalins whose thermodynamic stability is a key feature on their coupling to [Formula: see text] and [Formula: see text] receptors and the triggering of biochemical responses.

Free Energy and Structure of Helix-forming Peptides: A Theoretical Investigation

NASA Astrophysics Data System (ADS)

Karpusenka, Vadzim

This thesis focuses on the structure and free energy of helical secondary structures of short peptides in a variety of experimental settings. Specifically, the formation of alpha-, pi- and 310-helices was investigated using large-scale classical molecular dynamics simulations with state-of-the-art force fields. In addition, the recently developed Adaptively Biased Molecular Dynamics (ABMD) and Steered Molecular Dynamics (SMD) methods were used to calculate the corresponding free energies. The most important results are as follows. For the examined peptide homopolymers, the observed minima on the free energy landscapes (based on suitable collective variables such as the radius of gyration, number of hydrogen bonds, and handedness) were associated with alpha-helices and "globular" or "knot-like" configurations only. No evidence was found to indicate that 310- or pi-helices represent equilibrium structures for these systems. In addition, the free energy landscape of short peptide chains formed by mixing two different amino acids were also examined. These results too indicate that the alpha-helix is only equilibrium helical secondary structure, and that the mixing of different amino acids does not result in the introduction of any significant new minima into the free energy landscapes. These results are in agreement with experimental observations insofar as these indicate that helical structural motifs are primary based on alpha-helices, with 310- and pi-helices being observed only rarely. Although pi- and 310-helices represent nonequilibrium structures, we were still able to estimate their free energies by means of SMD simulations. The helical secondary structure of the examined polypeptide chains is due to the formation of hydrogen bonds. However, there are other mechanisms that may allow for the additional stabilization of these structures. Specifically, in the so-called AK-(4,7) protein, the possible presence of disulfide bonds connecting cysteine residues may significantly alter the free energy landscapes and therefore the stability of different helical structures. We therefore examined this issue with ABMD simulations. However, our results show that while the free energy landscapes are indeed significantly altered only the formation of alpha-helices is favored as a secondary structural motif. Since all the results indicate that alpha-helix formation dominates, it is natural to think in terms of an alpha-helix forming propensity for different amino acids. To address this question, we carried out an extensive residue-by-residue population analysis of different amino acid guests in an alanine-based host setting. Such an analysis allows us to rank the different amino acid guests based on whether they increased or decreased the population in the alpha-helix region of the corresponding Ramachandran plots. Our ranking of the different guest amino acids is in reasonable correspondence with the experimental results, although some differences are observed. Finally, using a four-beads coarse-grained model were have investigated the stability of GA88 and GB88 proteins, which are quite similar in terms of their amino acid sequence, by means of 10mus simulations. The results indicate that while the three alpha-helix bundle of the GA88 protein remains stable, the 2beta--alpha--2beta configuration of the GB88 protein does not: the latter rapidly converts to a structure consisting mostly of helices similar to the GA88 protein design. These results indicate that this particular four-bead coarse-grained model is not able to properly grasp the dynamics of the beta-sheet secondary structure and overstabilizes the corresponding helical content.

Chromatographic enantioseparation by poly(biphenylylacetylene) derivatives with memory of both axial chirality and macromolecular helicity.

PubMed

Ishidate, Ryoma; Ikai, Tomoyuki; Kanoh, Shigeyoshi; Yashima, Eiji; Maeda, Katsuhiro

2017-03-01

Novel poly(biphenylylacetylene) derivatives bearing two acetyloxy groups at the 2- and 2'-positions and an alkoxycarbonyl group at the 4'-position of the biphenyl pendants (poly-Ac's) were synthesized by the polymerization of the corresponding biphenylylacetylenes using a rhodium catalyst. The obtained stereoregular (cis-transoidal) poly-Ac's folded into a predominantly one-handed helical conformation accompanied by a preferred-handed axially twisted conformation of the biphenyl pendants through noncovalent interactions with a chiral alcohol and both the induced main-chain helicity and the pendant axial chirality were maintained, that is, memorized, after complete removal of the chiral alcohol. The stability of the helicity memory of the poly-Ac's in a solution was lower than that of the analogous poly(biphenylylacetylene)s bearing two methoxymethoxy groups at the 2- and 2'-positions of the biphenyl pendants (poly-MOM's). In the solid state, however, the helicity memory of the poly-Ac's was much more stable and showed a better chiral recognition ability toward several racemates than that of the previously reported poly-MOM when used as a chiral stationary phase for high-performance liquid chromatography. In particular, the poly-Ac-based CSP with a helicity memory efficiently separated racemic benzoin derivatives into enantiomers. © 2017 Wiley Periodicals, Inc.

Weak low-frequency electromagnetic oscillations in water.

PubMed

Liboff, A R; Poggi, Claudio; Pratesi, Piero

2017-01-01

Recent observations of low-frequency electromagnetic oscillations in water suggest an inductive structural component. Accordingly, we assume a helical basis enabling us to model water as an LC tuned oscillator. A proposed tetrahedral structure consisting of three water molecules and one hydronium ion is incorporated into the Boerdijk-Coxeter tetrahelix to form long water chains that are shown to have resonance frequencies consistent with observation. This model also serves to explain separately reported claims of ion cyclotron resonance of hydronium ions, in that the tetrahelix provides a built-in path for helical proton-hopping.

Folding and stability of helical bundle proteins from coarse-grained models.

PubMed

Kapoor, Abhijeet; Travesset, Alex

2013-07-01

We develop a coarse-grained model where solvent is considered implicitly, electrostatics are included as short-range interactions, and side-chains are coarse-grained to a single bead. The model depends on three main parameters: hydrophobic, electrostatic, and side-chain hydrogen bond strength. The parameters are determined by considering three level of approximations and characterizing the folding for three selected proteins (training set). Nine additional proteins (containing up to 126 residues) as well as mutated versions (test set) are folded with the given parameters. In all folding simulations, the initial state is a random coil configuration. Besides the native state, some proteins fold into an additional state differing in the topology (structure of the helical bundle). We discuss the stability of the native states, and compare the dynamics of our model to all atom molecular dynamics simulations as well as some general properties on the interactions governing folding dynamics. Copyright © 2013 Wiley Periodicals, Inc.

Anderson transition in a multiply-twisted helix.

PubMed

Ugajin, R

2001-06-01

We investigated the Anderson transition in a multiply-twisted helix in which a helical chain of components, i.e., atoms or nanoclusters, is twisted to produce a doubly-twisted helix, which itself can be twisted to produce a triply-twisted helix, and so on, in which there are couplings between adjacent rounds of helices. As the strength of the on-site random potentials increases, an Anderson transition occurs, suggesting that the number of dimensions is 3 for electrons running along the multiply-twisted helix when the couplings between adjacent rounds are strong enough. If the couplings are weakened, the dimensionality becomes less, resulting in localization of electrons. The effect of random connections between adjacent rounds of helices and random magnetic fields that thread the structure is analyzed using the spectral statistics of a quantum particle.

Hydrogen bonds and heat diffusion in α-helices: a computational study.

PubMed

Miño, German; Barriga, Raul; Gutierrez, Gonzalo

2014-08-28

Recent evidence has shown a correlation between the heat diffusion pathways and the known allosteric communication pathways in proteins. Allosteric communication in proteins is a central, yet unsolved, problem in biochemistry, and the study and characterization of the structural determinants that mediate energy transfer among different parts of proteins is of major importance. In this work, we characterized the role of hydrogen bonds in diffusivity of thermal energy for two sets of α-helices with different abilities to form hydrogen bonds. These hydrogen bonds can be a constitutive part of the α-helices or can arise from the lateral chains. In our in vacuo simulations, it was observed that α-helices with a higher possibility of forming hydrogen bonds also had higher rates of thermalization. Our simulations also revealed that heat readily flowed through atoms involved in hydrogen bonds. As a general conclusion, according to our simulations, hydrogen bonds fulfilled an important role in heat diffusion in structural patters of proteins.

Analytical study on the generalized Davydov model in the alpha helical proteins

NASA Astrophysics Data System (ADS)

Wang, Pan; Xiao, Shu-Hong; Chen, Li; Yang, Gang

2017-06-01

In this paper, we investigate the dynamics of a generalized Davydov model derived from an infinite chain of alpha helical protein molecules which contain three hydrogen bonding spines running almost parallel to the helical axis. Through the introduction of the auxiliary function, the bilinear form, one-, two- and three-soliton solutions for the generalized Davydov model are obtained firstly. Propagation and interactions of solitons have been investigated analytically and graphically. The amplitude of the soliton is only related to the complex parameter μ and real parameter 𝜃 with a range of [0, 2π]. The velocity of the soliton is only related to the complex parameter μ, real parameter 𝜃, lattice parameter 𝜀, and physical parameters β1, β3 and β4. Overtaking and head-on interactions of two and three solitons are presented. The common in the interactions of three solitons is the directions of the solitons change after the interactions. The soliton derived in this paper is expected to have potential applications in the alpha helical proteins.

Structural elucidation of a heteroglycan from the fruiting bodies of Agaricus blazei Murill.

PubMed

Liu, Jicheng; Zhang, Chunjing; Wang, Yajun; Yu, Haitao; Liu, Han; Wang, Liping; Yang, Xiuzhen; Liu, Zhecheng; Wen, Xianchun; Sun, Yongxu; Yu, Chunlei; Liu, Lei

2011-11-01

One water-soluble polysaccharide (ABP-W1) was purified from the fruiting bodies of Agaricus blazei by DEAE Sepharose Fast Flow and Sepharose 6 Fast Flow column chromatography. Its molecular weight was about 3.9×10(2) kDa as determined by high-performance size-exclusion chromatography (HPSEC). The structural feature of ABP-W1 was investigated by a combination of chemical and instrumental analysis, including partial hydrolysis with acid, periodate oxidation-Smith degradation, acetylation, methylation analysis and nuclear magnetic resonance spectroscopy (NMR (1)H, (13)C). The results revealed that ABP-W1 had a backbone consisting of (1→6)-linked-α-D-galactopyranosyl and (1→2,6)-linked-α-D-glucopyranosyl, which was branched with one single terminal (1→)-α-D-glucopyranosyl at the O-2 position of (1→2,6)-linked-α-D-glucopyranosyl along the main chain in the ratio of 1:1:1. The observation of the complex-formation between ABP-W1 and Congo Red indicated that ABP-W1 probably existed in a triple-strand helical conformation in water. Based on the data obtained, ABP-W1 was composed of a repeating unit with a structure as below: [structure: see text]. Copyright © 2011 Elsevier B.V. All rights reserved.

Ultraviolet-B radiation induced cross-linking improves physical properties of cold- and warm-water fish gelatin gels and films.

PubMed

Otoni, Caio G; Avena-Bustillos, Roberto J; Chiou, Bor-Sen; Bilbao-Sainz, Cristina; Bechtel, Peter J; McHugh, Tara H

2012-09-01

Cold- and warm-water fish gelatin granules were exposed to ultraviolet-B radiation for doses up to 29.7 J/cm(2). Solutions and films were prepared from the granules. Gel electrophoresis and refractive index were used to examine changes in molecular weight of the samples. Also, the gel strength and rheological properties of the solutions as well as the tensile and water vapor barrier properties of the films were characterized. SDS-PAGE and refractive index results indicated cross-linking of gelatin chains after exposure to radiation. Interestingly, UV-B treated samples displayed higher gel strengths, with cold- and warm-water fish gelatin having gel strength increases from 1.39 to 2.11 N and from 7.15 to 8.34 N, respectively. In addition, both gelatin samples exhibited an increase in viscosity for higher UV doses. For gelatin films, the cold-water fish gelatin samples made from irradiated granules showed greater tensile strength. In comparison, the warm-water gelatin films made from irradiated granules had lower tensile strength, but better water vapor barrier properties. This might be due to the UV induced cross-linking in warm-water gelatin that disrupted helical structures. Journal of Food Science copy; 2012 Institute of Food Technologists® No claim to original US government works.

Characterization and bioactivities of a novel polysaccharide obtained from Gracilariopsis lemaneiformis.

PubMed

Shi, Chen-Shan; Sang, Ya-Xin; Sun, Gui-Qing; Li, Tian-Ye; Gong, Zheng-Si; Wang, Xiang-Hong

2017-01-01

Gracilariopsis lemaneiformis is a type of red alga that contains seaweed polysaccharide agar. In this study, a novel non-agar seaweed polysaccharide fraction named GCP (short of crude polysaccharide obtained from Gracilariopsis lemaneiformis) was isolated from Gracilariopsis lemaneiformis. Structural analysis showed that GCP shows triple helical chain conformation when dissolved in water and has many branches and long side chains. Also, 1→3 linkage is the major linkage and the sugar structures are galactopyranose configurations linked by β-type glycosidic linkages. Two macromolecular substance fractions (GCP-1 and GCP-2) were purified by DEAE Sepharose Fast Flow column chromatography. Moreover, a splenocyte damage assay and splenocyte proliferation assay were used to analyse the bioactivities of GCP, GCP-1 and GCP-2. It was demonstrated that polysaccharides could protect splenocyte damaged by H2O2; GCP-2 shows a greatest protection rate, that is, 92.8%, which significantly enhanced the splenocyte proliferation, and GCP showed the highest proliferation rate, 9.30%. The results suggested that this type of novel non-agar polysaccharide displayed remarkable antioxidant and immunomodulatory activities and early alkali treatment could decrease the activities. It may represent a potential material for health food and clinical medicines.

Crystal Structure of Phosphatidylglycerophosphatase (PGPase), a Putative Membrane-Bound Lipid Phosphatase, Reveals a Novel Binuclear Metal Binding Site and Two Proton Wires

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumaran,D.; Bonnano, J.; Burley, S.

2006-01-01

Phosphatidylglycerophosphatase (PGPase), an enzyme involved in lipid metabolism, catalyzes formation of phosphatidylglycerol from phosphatidylglycerophosphate. Phosphatidylglycerol is a multifunctional phospholipid, found in the biological membranes of many organisms. Here, we report the crystal structure of Listeria monocytogenes PGPase at 1.8 Angstroms resolution. PGPase, an all-helical molecule, forms a homotetramer. Each protomer contains an independent active site with two metal ions, Ca{sup 2+} and Mg{sup 2+}, forming a hetero-binuclear center located in a hydrophilic cavity near the surface of the molecule. The binuclear center, conserved ligands, metal-bound water molecules, and an Asp-His dyad form the active site. The catalytic mechanism of thismore » enzyme is likely to proceed via binuclear metal activated nucleophilic water. The binuclear metal-binding active-site environment of this structure should provide insights into substrate binding and metal-dependent catalysis. A long channel with inter-linked linear water chains, termed 'proton wires', is observed at the tetramer interface. Comparison of similar water chain structures in photosynthetic reaction centers (RCs), Cytochrome f, gramicidin, and bacteriorhodopsin, suggests that PGPase may conduct protons via proton wires.« less

Four unprecedented cobalt(II) and cadmium(II) metal-organic frameworks based on a rigid tricarboxylate ligand: Synthesis, crystal structures, magnetic and fluorescence properties

NASA Astrophysics Data System (ADS)

Liu, Yaru; Liu, Lan; Zhang, Xiao; Wu, Jie

2018-03-01

A Co(II) MOF {[Co3(L)2(H2O)4](DMF)2}n (1) and three Cd(II) MOFs [Cd3(L)2(H2O)7]n (2), [Cd3(L)2(H2O)11]n (3) and [Cd3(L)2(DMF)2(H2O)]n (4) are synthesized based on the promising multifunctional tricarboxylate ligand 6-(3, 5-dicarboxyl phenyl) nicotinic acid (H3L). 1 exhibits a 3D framework with 1D channels which contains opposite-handedness helical chains based on the trinuclear Co(II) clusters. 2-4 are obtained depend on different reaction conditions. 2 displays a 3D framework, which is composed of two kinds of 2D layers linked with each other. 3 shows a rare tongue-and-groove-type bilayer structure. And 4 is an interesting 3D framework containing infinite 1D inorganic Cdsbnd Osbnd Cd chains. In these MOFs, the H3L ligand shows the versatile coordination modes and strong coordination ability. Furthermore, the magnetic and solid-state luminescent properties of the MOFs have been investigated.

Mechanism of insulin fibrillation: the structure of insulin under amyloidogenic conditions resembles a protein-folding intermediate.

PubMed

Hua, Qing-xin; Weiss, Michael A

2004-05-14

Insulin undergoes aggregation-coupled misfolding to form a cross-beta assembly. Such fibrillation has long complicated its manufacture and use in the therapy of diabetes mellitus. Of interest as a model for disease-associated amyloids, insulin fibrillation is proposed to occur via partial unfolding of a monomeric intermediate. Here, we describe the solution structure of human insulin under amyloidogenic conditions (pH 2.4 and 60 degrees C). Use of an enhanced sensitivity cryogenic probe at high magnetic field avoids onset of fibrillation during spectral acquisition. A novel partial fold is observed in which the N-terminal segments of the A- and B-chains detach from the core. Unfolding of the N-terminal alpha-helix of the A-chain exposes a hydrophobic surface formed by native-like packing of the remaining alpha-helices. The C-terminal segment of the B-chain, although not well ordered, remains tethered to this partial helical core. We propose that detachment of N-terminal segments makes possible aberrant protein-protein interactions in an amyloidogenic nucleus. Non-cooperative unfolding of the N-terminal A-chain alpha-helix resembles that observed in models of proinsulin folding intermediates and foreshadows the extensive alpha --> beta transition characteristic of mature fibrils.

Computational prediction of atomic structures of helical membrane proteins aided by EM maps.

PubMed

Kovacs, Julio A; Yeager, Mark; Abagyan, Ruben

2007-09-15

Integral membrane proteins pose a major challenge for protein-structure prediction because only approximately 100 high-resolution structures are available currently, thereby impeding the development of rules or empirical potentials to predict the packing of transmembrane alpha-helices. However, when an intermediate-resolution electron microscopy (EM) map is available, it can be used to provide restraints which, in combination with a suitable computational protocol, make structure prediction feasible. In this work we present such a protocol, which proceeds in three stages: 1), generation of an ensemble of alpha-helices by flexible fitting into each of the density rods in the low-resolution EM map, spanning a range of rotational angles around the main helical axes and translational shifts along the density rods; 2), fast optimization of side chains and scoring of the resulting conformations; and 3), refinement of the lowest-scoring conformations with internal coordinate mechanics, by optimizing the van der Waals, electrostatics, hydrogen bonding, torsional, and solvation energy contributions. In addition, our method implements a penalty term through a so-called tethering map, derived from the EM map, which restrains the positions of the alpha-helices. The protocol was validated on three test cases: GpA, KcsA, and MscL.

Transmembrane helix prediction: a comparative evaluation and analysis.

PubMed

Cuthbertson, Jonathan M; Doyle, Declan A; Sansom, Mark S P

2005-06-01

The prediction of transmembrane (TM) helices plays an important role in the study of membrane proteins, given the relatively small number (approximately 0.5% of the PDB) of high-resolution structures for such proteins. We used two datasets (one redundant and one non-redundant) of high-resolution structures of membrane proteins to evaluate and analyse TM helix prediction. The redundant (non-redundant) dataset contains structure of 434 (268) TM helices, from 112 (73) polypeptide chains. Of the 434 helices in the dataset, 20 may be classified as 'half-TM' as they are too short to span a lipid bilayer. We compared 13 TM helix prediction methods, evaluating each method using per segment, per residue and termini scores. Four methods consistently performed well: SPLIT4, TMHMM2, HMMTOP2 and TMAP. However, even the best methods were in error by, on average, about two turns of helix at the TM helix termini. The best and worst case predictions for individual proteins were analysed. In particular, the performance of the various methods and of a consensus prediction method, were compared for a number of proteins (e.g. SecY, ClC, KvAP) containing half-TM helices. The difficulties of predicting half-TM helices suggests that current prediction methods successfully embody the two-state model of membrane protein folding, but do not accommodate a third stage in which, e.g., short helices and re-entrant loops fold within a bundle of stable TM helices.

Role of bundle helices in a regulatory crosstalk in the trimeric betaine transporter BetP.

PubMed

Gärtner, Rebecca M; Perez, Camilo; Koshy, Caroline; Ziegler, Christine

2011-12-02

The Na(+)-coupled betaine symporter BetP regulates transport activity in response to hyperosmotic stress only in its trimeric state, suggesting a regulatory crosstalk between individual protomers. BetP shares the overall fold of two inverted structurally related five-transmembrane (TM) helix repeats with the sequence-unrelated Na(+)-coupled symporters LeuT, vSGLT, and Mhp1, which are neither trimeric nor regulated in transport activity. Conformational changes characteristic for this transporter fold involve the two first helices of each repeat, which form a four-TM-helix bundle. Here, we identify two ionic networks in BetP located on both sides of the membrane that might be responsible for BetP's unique regulatory behavior by restricting the conformational flexibility of the four-TM-helix bundle. The cytoplasmic ionic interaction network links both first helices of each repeat in one protomer to the osmosensing C-terminal domain of the adjacent protomer. Moreover, the periplasmic ionic interaction network conformationally locks the four-TM-helix bundle between the same neighbor protomers. By a combination of site-directed mutagenesis, cross-linking, and betaine uptake measurements, we demonstrate how conformational changes in individual bundle helices are transduced to the entire bundle by specific inter-helical interactions. We suggest that one purpose of bundle networking is to assist crosstalk between protomers during transport regulation by specifically modulating the transition from outward-facing to inward-facing state. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen*

PubMed Central

Terajima, Masahiko; Taga, Yuki; Chen, Yulong; Cabral, Wayne A.; Hou-Fu, Guo; Srisawasdi, Sirivimol; Nagasawa, Masako; Sumida, Noriko; Hattori, Shunji; Kurie, Jonathan M.; Marini, Joan C.; Yamauchi, Mitsuo

2016-01-01

Covalent intermolecular cross-linking provides collagen fibrils with stability. The cross-linking chemistry is tissue-specific and determined primarily by the state of lysine hydroxylation at specific sites. A recent study on cyclophilin B (CypB) null mice, a model of recessive osteogenesis imperfecta, demonstrated that lysine hydroxylation at the helical cross-linking site of bone type I collagen was diminished in these animals (Cabral, W. A., Perdivara, I., Weis, M., Terajima, M., Blissett, A. R., Chang, W., Perosky, J. E., Makareeva, E. N., Mertz, E. L., Leikin, S., Tomer, K. B., Kozloff, K. M., Eyre, D. R., Yamauchi, M., and Marini, J. C. (2014) PLoS Genet. 10, e1004465). However, the extent of decrease appears to be tissue- and molecular site-specific, the mechanism of which is unknown. Here we report that although CypB deficiency resulted in lower lysine hydroxylation in the helical cross-linking sites, it was increased in the telopeptide cross-linking sites in tendon type I collagen. This resulted in a decrease in the lysine aldehyde-derived cross-links but generation of hydroxylysine aldehyde-derived cross-links. The latter were absent from the wild type and heterozygous mice. Glycosylation of hydroxylysine residues was moderately increased in the CypB null tendon. We found that CypB interacted with all lysyl hydroxylase isoforms (isoforms 1–3) and a putative lysyl hydroxylase-2 chaperone, 65-kDa FK506-binding protein. Tendon collagen in CypB null mice showed severe size and organizational abnormalities. The data indicate that CypB modulates collagen cross-linking by differentially affecting lysine hydroxylation in a site-specific manner, possibly via its interaction with lysyl hydroxylases and associated molecules. This study underscores the critical importance of collagen post-translational modifications in connective tissue formation. PMID:26934917

Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen.

PubMed

Terajima, Masahiko; Taga, Yuki; Chen, Yulong; Cabral, Wayne A; Hou-Fu, Guo; Srisawasdi, Sirivimol; Nagasawa, Masako; Sumida, Noriko; Hattori, Shunji; Kurie, Jonathan M; Marini, Joan C; Yamauchi, Mitsuo

2016-04-29

Covalent intermolecular cross-linking provides collagen fibrils with stability. The cross-linking chemistry is tissue-specific and determined primarily by the state of lysine hydroxylation at specific sites. A recent study on cyclophilin B (CypB) null mice, a model of recessive osteogenesis imperfecta, demonstrated that lysine hydroxylation at the helical cross-linking site of bone type I collagen was diminished in these animals (Cabral, W. A., Perdivara, I., Weis, M., Terajima, M., Blissett, A. R., Chang, W., Perosky, J. E., Makareeva, E. N., Mertz, E. L., Leikin, S., Tomer, K. B., Kozloff, K. M., Eyre, D. R., Yamauchi, M., and Marini, J. C. (2014) PLoS Genet 10, e1004465). However, the extent of decrease appears to be tissue- and molecular site-specific, the mechanism of which is unknown. Here we report that although CypB deficiency resulted in lower lysine hydroxylation in the helical cross-linking sites, it was increased in the telopeptide cross-linking sites in tendon type I collagen. This resulted in a decrease in the lysine aldehyde-derived cross-links but generation of hydroxylysine aldehyde-derived cross-links. The latter were absent from the wild type and heterozygous mice. Glycosylation of hydroxylysine residues was moderately increased in the CypB null tendon. We found that CypB interacted with all lysyl hydroxylase isoforms (isoforms 1-3) and a putative lysyl hydroxylase-2 chaperone, 65-kDa FK506-binding protein. Tendon collagen in CypB null mice showed severe size and organizational abnormalities. The data indicate that CypB modulates collagen cross-linking by differentially affecting lysine hydroxylation in a site-specific manner, possibly via its interaction with lysyl hydroxylases and associated molecules. This study underscores the critical importance of collagen post-translational modifications in connective tissue formation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A Solid-State Deuterium NMR and SFG Study of the Side Chain Dynamics of Peptides Adsorbed onto Surfaces

PubMed Central

Breen, Nicholas F.; Weidner, Tobias; Li, Kun; Castner, David G.; Drobny, Gary P.

2011-01-01

The artificial amphiphilic peptide LKα14 adopts a helical structure at interfaces, with opposite orientation of its leucine (L, hydrophobic) and lysine (K, hydrophilic) side chains. When adsorbed onto surfaces, different residue side chains necessarily have different proximities to the surface, depending on both their position in the helix and the composition of the surface itself. Deuterating the individual leucine residues (isopropyl-d7) permits the use of solid-state deuterium NMR as a site-specific probe of side chain dynamics. In conjunction with SFG as a probe of the peptide binding face, we demonstrate that the mobility of specific leucine side chains at the interface is quantifiable in terms of their surface proximity. PMID:19764755

Computer Simulations of Polytetrafluoroethylene in the Solid State

NASA Astrophysics Data System (ADS)

Holt, D. B.; Farmer, B. L.; Eby, R. K.; Macturk, K. S.

1996-03-01

Force field parameters (Set I) for fluoropolymers were previously derived from MOPAC AM1 semiempirical data on model molecules. A second set (Set II) was derived from the AM1 results augmented by ab initio calculations. Both sets yield reasonable helical and phase II packing structures for polytetrafluoroethylene (PTFE) chains. However, Set I and Set II differ in the strength of van der Waals interactions, with Set II having deeper potential wells (order of magnitude). To differentiate which parameter set provides a better description of PTFE behavior, molecular dynamics simulations have been performed with Biosym Discover on clusters of PTFE chains which begin in a phase II packing environment. Added to the model are artificial constraints which allow the simulation of thermal expansion without having to define periodic boundary conditions for each specific temperature of interest. The preliminary dynamics simulations indicate that the intra- and intermolecular interactions provided by Set I are too weak. The degree of helical disorder and chain motion are high even at temperatures well below the phase II-phase IV transition temperature (19 C). Set II appears to yield a better description of PTFE in the solid state.

Consortium for Osteogenesis Imperfecta Mutations in the Helical Domain of Type I Collagen: Regions Rich in Lethal Mutations Align With Collagen Binding Sites for Integrins and Proteoglycans

PubMed Central

Marini, Joan C.; Forlino, Antonella; Cabral, Wayne A.; Barnes, Aileen M.; San Antonio, James D.; Milgrom, Sarah; Hyland, James C.; Körkkö, Jarmo; Prockop, Darwin J.; De Paepe, Anne; Coucke, Paul; Symoens, Sofie; Glorieux, Francis H.; Roughley, Peter J.; Lund, Alan M.; Kuurila-Svahn, Kaija; Hartikka, Heini; Cohn, Daniel H.; Krakow, Deborah; Mottes, Monica; Schwarze, Ulrike; Chen, Diana; Yang, Kathleen; Kuslich, Christine; Troendle, James; Dalgleish, Raymond; Byers, Peter H.

2014-01-01

Osteogenesis imperfecta (OI) is a generalized disorder of connective tissue characterized by fragile bones and easy susceptibility to fracture. Most cases of OI are caused by mutations in type I collagen. We have identified and assembled structural mutations in type I collagen genes (COL1A1 and COL1A2, encoding the proα1(I) and proα2(I) chains, respectively) that result in OI. Quantitative defects causing type I OI were not included. Of these 832 independent mutations, 682 result in substitution for glycine residues in the triple helical domain of the encoded protein and 150 alter splice sites. Distinct genotype–phenotype relationships emerge for each chain. One-third of the mutations that result in glycine substitutions in α1(I) are lethal, especially when the substituting residues are charged or have a branched side chain. Substitutions in the first 200 residues are nonlethal and have variable outcome thereafter, unrelated to folding or helix stability domains. Two exclusively lethal regions (helix positions 691–823 and 910–964) align with major ligand binding regions (MLBRs), suggesting crucial interactions of collagen monomers or fibrils with integrins, matrix metalloproteinases (MMPs), fibronectin, and cartilage oligomeric matrix protein (COMP). Mutations in COL1A2 are predominantly nonlethal (80%). Lethal substitutions are located in eight regularly spaced clusters along the chain, supporting a regional model. The lethal regions align with proteoglycan binding sites along the fibril, suggesting a role in fibril–matrix interactions. Recurrences at the same site in α2(I) are generally concordant for outcome, unlike α1(I). Splice site mutations comprise 20% of helical mutations identified in OI patients, and may lead to exon skipping, intron inclusion, or the activation of cryptic splice sites. Splice site mutations in COL1A1 are rarely lethal; they often lead to frameshifts and the mild type I phenotype. In α2(I), lethal exon skipping events are located in the carboxyl half of the chain. Our data on genotype–phenotype relationships indicate that the two collagen chains play very different roles in matrix integrity and that phenotype depends on intracellular and extracellular events. PMID:17078022

Optimizing an undulating magnetic microswimmer for cargo towing

NASA Astrophysics Data System (ADS)

Or, Yizhar; Gutman, Emiliya

2015-11-01

One of the promising applications of robotic microswimmers is towing a cargo for controlled drug delivery, micro-surgery or tumor detection. This capability has been demonstrated by the magnetically-actuated microswimmer of Dreyfus et al. [Nature 2005] in which a red blood cell was attached to a chain of magnetic beads connected by flexible DNA links. A key question is what should be the optimal size of the magnetic tail for towing a given cargo. This question is addressed here for the simplest theoretical model of a magnetic microswimmer under planar undulations - a spherical load connected by a torsion spring to a magnetized rigid slender link. The swimmer's dynamics is formulated assuming negligible hydrodynamic interaction and leading-order expressions for the resulting motion are obtained explicitly under small amplitude approximation. Optimal combinations of magnetic actuation frequency, torsion stiffness, and tail length for maximizing displacement or average speed are obtained. The theoretical results are compared with several reported magnetic microswimmers, and also agree qualitatively with recent results on cargo towing by screw rotation of magnetic helical tails [Walker et al., ACS Nano Letters 2015]. This work is supported by the Israeli Science Foundation (ISF) under Grant No. 567/14.

Folding and trimerization of clathrin subunits at the triskelion hub.

PubMed

Näthke, I S; Heuser, J; Lupas, A; Stock, J; Turck, C W; Brodsky, F M

1992-03-06

The triskelion shape of the clathrin molecule enables it to form the polyhedral protein network that covers clathrin-coated pits and vesicles. Domains within the clathrin heavy chain that are responsible for maintaining triskelion shape and function were identified and localized. Sequences that mediate trimerization are distal to the carboxyl terminus and are adjacent to a domain that mediates both light chain binding and clathrin assembly. Structural modeling predicts that within this domain, the region of heavy chain-light chain interaction is a bundle of three or four alpha helices. These studies establish a low resolution model of clathrin subunit folding in the central portion (hub) of the triskelion, thus providing a basis for future mutagenesis experiments.

Unraveling double stranded alpha-helical coiled coils: an x-ray diffraction study on hard alpha-keratin fibers.

PubMed

Kreplak, L; Doucet, J; Briki, F

2001-04-15

Transformations of proteins secondary and tertiary structures are generally studied in globular proteins in solution. In fibrous proteins, such as hard alpha-keratin, that contain long and well-defined double stranded alpha-helical coiled coil domains, such study can be directly done on the native fibrous tissue. In order to assess the structural behavior of the coiled coil domains under an axial mechanical stress, wide angle x-ray scattering and small angle x-ray scattering experiments have been carried out on stretched horse hair fibers at relative humidity around 30%. Our observations of the three major axial spacings as a function of the applied macroscopic strain have shown two rates. Up to 4% macroscopic strain the coiled coils were slightly distorted but retained their overall conformation. Above 4% the proportion of coiled coil domains progressively decreased. The main and new result of our study is the observation of the transition from alpha-helical coiled coils to disordered chains instead of the alpha-helical coiled coil to beta-sheet transition that occurs in wet fibers.

A tendril perversion in a helical oligomer: trapping and characterizing a mobile screw-sense reversal† †Electronic supplementary information (ESI) available. CCDC X-ray crystal data for 1a and 1b have been deposited with the CCDC, deposition numbers 1518806 and 1518807. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc05474a Click here for additional data file. Click here for additional data file.

PubMed Central

Tomsett, Michael; Maffucci, Irene; Le Bailly, Bryden A. F.; Byrne, Liam; Bijvoets, Stefan M.; Lizio, M. Giovanna; Raftery, James; Butts, Craig P.; Webb, Simon J.; Contini, Alessandro

2017-01-01

Helical oligomers of achiral monomers adopt domains of uniform screw sense, which are occasionally interrupted by screw-sense reversals. These rare, elusive, and fast-moving features have eluded detailed characterization. We now describe the structure and habits of a screw-sense reversal trapped within a fragment of a helical oligoamide foldamer of the achiral quaternary amino acid 2-aminoisobutyric acid (Aib). The reversal was enforced by compelling the amide oligomer to adopt a right-handed screw sense at one end and a left-handed screw sense at the other. The trapped reversal was characterized by X-ray crystallography, and its dynamic properties were monitored by NMR and circular dichroism, and modelled computationally. Raman spectroscopy indicated that a predominantly helical architecture was maintained despite the reversal. NMR and computational results indicated a stepwise shift from one screw sense to another on moving along the helical chain, indicating that in solution the reversal is not localised at a specific location, but is free to migrate across a number of residues. Analogous unconstrained screw-sense reversals that are free to move within a helical structure are likely to provide the mechanism by which comparable helical polymers and foldamers undergo screw-sense inversion. PMID:28451368

Co-assembly of Zn(SPh){sub 2} and organic linkers into helical and zig-zag polymer chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Yi; Yu Lingmin; Loo, Say Chye Joachim

2012-07-15

Two novel one-dimensional coordination polymers, single helicate [Zn(SPh){sub 2}(TPyTA)(EG)]{sub n} (EG=ethylene glycol) (1) and zig-zag structure [Zn(SPh){sub 2}(BPyVB)]{sub n} (2), were synthesized under solvothermal conditions at 150 Degree-Sign C or room temperature by the co-assembly of Zn(SPh){sub 2} and organic linkers such as 2,4,6-tri(4-pyridyl)-1,3,5-triazine (TPyTA) and 1,3-bis(trans-4-pyridylvinyl)benzene (BPyVB). X-ray crystallography study reveals that both polymers 1 and 2 crystallize in space group P2{sub 1}/c of the monoclinic system. The solid-state UV-vis absorption spectra show that 1 and 2 have maxium absorption onsets at 400 nm and 420 nm, respectively. TGA analysis indicates that 1 and 2 are stable up tomore » 110 Degree-Sign C and 210 Degree-Sign C. - Graphical abstract: Two novel one-dimensional coordination polymers, single helicate [Zn(SPh){sub 2}(TPyTA)(EG)]{sub n} (1) and zig-zag structure [Zn(SPh){sub 2}(BPyVB)]{sub n} (2), were synthesized. Solid-state UV-vis absorptions show that 1 and 2 have maxium absorption onsets at 400 nm and 420 nm, respectively. TGA analysis indicates that 1 and 2 are stable up to 110 Degree-Sign C and 210 Degree-Sign C. Highlights: Black-Right-Pointing-Pointer Two novel one-dimensional coordination polymers have been synthesized. Black-Right-Pointing-Pointer TPyTA results in helical structures in 1 while BPyVB leads to zig-zag chains in 2. Black-Right-Pointing-Pointer Solid-state UV-vis absorption spectra and TGA analysis of the title polymers were studied.« less

Effect of double-tailed surfactant architecture on the conformation, self-assembly, and processing in polypeptide-surfactant complexes.

PubMed

Junnila, Susanna; Hanski, Sirkku; Oakley, Richard J; Nummelin, Sami; Ruokolainen, Janne; Faul, Charl F J; Ikkala, Olli

2009-10-12

This work describes the solid-state conformational and structural properties of self-assembled polypeptide-surfactant complexes with double-tailed surfactants. Poly(L-lysine) was complexed with three dialkyl esters of phosphoric acid (i.e., phosphodiester surfactants), where the surfactant tail branching and length was varied to tune the supramolecular architecture in a facile way. After complexation with the branched surfactant bis(2-ethylhexyl) phosphate in an aqueous solution, the polypeptide chains adopted an alpha-helical conformation. These rod-like helices self-assembled into cylindrical phases with the amorphous alkyl tails pointing outward. In complexes with dioctyl phosphate and didodecyl phosphate, which have two linear n-octyl or n-dodecyl tails, respectively, the polypeptide formed antiparallel beta-sheets separated by alkyl layers, resulting in well-ordered lamellar self-assemblies. By heating, it was possible to trigger a partial opening of the beta-sheets and disruption of the lamellar phase. After repeated heating/cooling, all of these complexes also showed a glass transition between 37 and 50 degrees C. Organic solvent treatment and plasticization by overstoichiometric amount of surfactant led to structure modification in poly(L-lysine)-dioctyl phosphate complexes, PLL(diC8)(x) (x = 1.0-3.0). Here, the alpha-helical PLL is surrounded by the surfactants and these bottle-brush-like chains self-assemble in a hexagonal cylindrical morphology. As x is increased, the materials are clearly plasticized and the degree of ordering is improved: The stiff alpha-helical backbones in a softened surfactant matrix give rise to thermotropic liquid-crystalline phases. The complexes were examined by Fourier transform infrared spectroscopy, small- and wide-angle X-ray scattering, transmission electron microscopy, differential scanning calorimetry, polarized optical microscopy, and circular dichroism.

Protein-linked Ubiquitin Chain Structure Restricts Activity of Deubiquitinating Enzymes*

PubMed Central

Schaefer, Jonathan B.; Morgan, David O.

2011-01-01

The attachment of lysine 48 (Lys48)-linked polyubiquitin chains to proteins is a universal signal for degradation by the proteasome. Here, we report that long Lys48-linked chains are resistant to many deubiquitinating enzymes (DUBs). Representative enzymes from this group, Ubp15 from yeast and its human ortholog USP7, rapidly remove mono- and diubiquitin from substrates but are slow to remove longer Lys48-linked chains. This resistance is lost if the structure of Lys48-linked chains is disrupted by mutation of ubiquitin or if chains are linked through Lys63. In contrast to Ubp15 and USP7, Ubp12 readily cleaves the ends of long chains, regardless of chain structure. We propose that the resistance to many DUBs of long, substrate-attached Lys48-linked chains helps ensure that proteins are maintained free from ubiquitin until a threshold of ubiquitin ligase activity enables degradation. PMID:22072716

Computational Prediction of Atomic Structures of Helical Membrane Proteins Aided by EM Maps

PubMed Central

Kovacs, Julio A.; Yeager, Mark; Abagyan, Ruben

2007-01-01

Integral membrane proteins pose a major challenge for protein-structure prediction because only ≈100 high-resolution structures are available currently, thereby impeding the development of rules or empirical potentials to predict the packing of transmembrane α-helices. However, when an intermediate-resolution electron microscopy (EM) map is available, it can be used to provide restraints which, in combination with a suitable computational protocol, make structure prediction feasible. In this work we present such a protocol, which proceeds in three stages: 1), generation of an ensemble of α-helices by flexible fitting into each of the density rods in the low-resolution EM map, spanning a range of rotational angles around the main helical axes and translational shifts along the density rods; 2), fast optimization of side chains and scoring of the resulting conformations; and 3), refinement of the lowest-scoring conformations with internal coordinate mechanics, by optimizing the van der Waals, electrostatics, hydrogen bonding, torsional, and solvation energy contributions. In addition, our method implements a penalty term through a so-called tethering map, derived from the EM map, which restrains the positions of the α-helices. The protocol was validated on three test cases: GpA, KcsA, and MscL. PMID:17496035

Exerting control over the helical chirality in the main chain of sergeants-and-soldiers-type poly(quinoxaline-2,3-diyl)s by changing from random to block copolymerization protocols.

PubMed

Nagata, Yuuya; Nishikawa, Tsuyoshi; Suginome, Michinori

2015-04-01

Chiral random poly(quinoxaline-2,3-diyl) polymers of the sergeants-and-soldiers-type (sergeant units bearing (S)-3-octyloxymethyl groups) adopt an M- or P-helical conformation in the presence of achiral units bearing propoxymethyl or butoxy groups (soldier units), respectively. Unusual bidirectional induction of the helical sense can be observed for a copolymer with butoxy soldier units upon changing the mole fraction of the sergeant units. In the presence of 16-20% of sergeant units, the selective induction of a P-helix was observed, while the selective induction of an M-helix was observed for a mole fraction of sergeant units of more than 60%. This phenomenon could be successfully employed to control the helical chirality of copolymers by applying either random or block copolymerization protocols. Random or block copolymerization of sergeant and soldier monomers in a 18:82 ratio resulted in the formation of 250mers with almost absolute P- or M-helical conformation, respectively (>99% ee). Incorporation of a small amount of coordination sites into the random and block copolymers resulted in chiral macromolecular ligands, which allowed the enantioselective synthesis of both enantiomers in the Pd-catalyzed asymmetric hydrosilylation of β-methylstyrene.

Nanostructure Control of Biologically Inspired Polymers

NASA Astrophysics Data System (ADS)

Rosales, Adrianne Marie

Biological polymers, such as polypeptides, are responsible for many of life's most sophisticated functions due to precisely evolved hierarchical structures. These protein structures are the result of monodisperse sequences of amino acids that fold into well-defined chain shapes and tertiary structures. Recently, there has been much interest in the design of such sequence-specific polymers for materials applications in fields ranging from biotechnology to separations membranes. Non-natural polymers offer the stability and robustness necessary for materials applications; however, our ability to control monomer sequence in non-natural polymers has traditionally operated on a much simpler level. In addition, the relationship between monomer sequence and self-assembly is not well understood for biological molecules, much less synthetic polymers. Thus, there is a need to explore self-assembly phase space with sequence using a model system. Polypeptoids are non-natural, sequence-specific polymers that offer the opportunity to probe the effect of sequence on self-assembly. A variety of monomer interactions have an impact on polymer properties, such as chirality, hydrophobicity, and electrostatic interactions. Thus, a necessary starting point for this project was to investigate monomer sequence effects on the bulk properties of polypeptoid homopolymers. It was found that several polypeptoids have experimentally accessible melting transitions that are dependent on the choice of side chains, and it was shown that this transition is tuned by the incorporation of "defects" or a comonomer. The polypeptoid chain shape is also controlled with the choice of monomer and monomer sequence. By using at least 50% monomers with bulky, chiral side chains, the polypeptoid backbone is sterically twisted into a helix, and as found for the first time in this work, the persistence length is increased. However, this persistence length, which is a measure of the stiffness of the polymer, is small compared to other folded helices, indicating the conformational flexibility of polypeptoid chains. With a firmer understanding of how monomer sequence and composition influence polypeptoid bulk properties, we designed block copolymer systems for self-assembly. Because the governing parameters of block copolymer self-assembly are well understood, this architecture provides a convenient starting point for probing the effect of changing polymer sequence. We found that polystyrene-polypeptoid block copolymers readily self-assemble into hexagonally-packed and lamellar morphologies with long range order, and furthermore, sequence control of the polypeptoid block enables us to tune the strength of segregation (and therefore the order-disorder transition) of the block copolymer. Polypeptoid chain shape also affects self-assembly. In classical synthetic block copolymers, it has typically been difficult to change chain shape without also changing polymer chemistry and therefore other factors affecting self-assembly. The advantage of the polypeptoid system is that it is modular, as the side chain chemistry (and therefore polymer properties) can easily be changed without changing the backbone chemistry. Thus, we have decoupled conformational effects from chemical composition by comparing the self-assembly of block copolymers containing either a helical peptoid block or its racemic, non-helical analog. The increase in the persistence length of the peptoid block due to helicity translates to an increase in the morphological domain spacing. In this work, we further the understanding of the effect of monomer sequence on bulk polypeptoid properties and self-assembly. Our findings pave the way for the rational design of structured synthetic polymers with tunable, sequence-specific properties.

Theoretical description of the decays Λb→Λ(*)(1/2±,3/2±)+J /ψ

NASA Astrophysics Data System (ADS)

Gutsche, Thomas; Ivanov, Mikhail A.; Körner, Jürgen G.; Lyubovitskij, Valery E.; Lyubushkin, Vladimir V.; Santorelli, Pietro

2017-07-01

We calculate the invariant and helicity amplitudes for the transitions Λb→Λ(*)(JP)+J /ψ , where the Λ(*)(JP) are Λ (s u d )-type ground and excited states with JP quantum numbers JP=1/2± , 3/2± . The calculations are performed in the framework of a covariant confined quark model previously developed by us. We find that the values of the helicity amplitudes for the Λ*(1520 ,3/2-) and the Λ*(1890 ,3/2+) are suppressed compared with those for the ground state Λ (1116 ,1/2+) and the excited state Λ*(1405 ,1/2-). This analysis is important for the identification of the hidden charm pentaquark states Pc+(4380 ) and Pc+(4450 ) which were discovered in the decay chain Λb0→Pc+(→p J /ψ )+K- because the cascade decay chain Λb→Λ*(3/2±)(→p K-)+J /ψ involves the same final state.

Converting One-Face α-Helix Mimetics into Amphiphilic α-Helix Mimetics as Potent Inhibitors of Protein-Protein Interactions.

PubMed

Lee, Ji Hoon; Oh, Misook; Kim, Hyun Soo; Lee, Huisun; Im, Wonpil; Lim, Hyun-Suk

2016-01-11

Many biologically active α-helical peptides adopt amphiphilic helical structures that contain hydrophobic residues on one side and hydrophilic residues on the other side. Therefore, α-helix mimetics capable of mimicking such amphiphilic helical peptides should possess higher binding affinity and specificity to target proteins. Here we describe an efficient method for generating amphiphilic α-helix mimetics. One-face α-helix mimetics having hydrophobic side chains on one side was readily converted into amphiphilic α-helix mimetics by introducing appropriate charged residues on the opposite side. We also demonstrate that such two-face amphiphilic α-helix mimetics indeed show remarkably improved binding affinity to a target protein, compared to one-face hydrophobic α-helix mimetics. We believe that generating a large combinatorial library of these amphiphilic α-helix mimetics can be valuable for rapid discovery of highly potent and specific modulators of protein-protein interactions.

On the energy density of helical proteins.

PubMed

Barros, Manuel; Ferrández, Angel

2014-12-01

We solve the problem of determining the energy actions whose moduli space of extremals contains the class of Lancret helices with a prescribed slope. We first see that the energy density should be linear both in the total bending and in the total twisting, such that the ratio between the weights of them is the prescribed slope. This will give an affirmative answer to the conjecture stated in Barros and Ferrández (J Math Phys 50:103529, 2009). Then, we normalize to get the best choice for the helical energy. It allows us to show that the energy, for instance of a protein chain, does not depend on the slope and is invariant under homotopic changes of the cross section which determines the cylinder where the helix is lying. In particular, the energy of a helix is not arbitrary, but it is given as natural multiples of some basic quantity of energy.

High-resolution structures of a heterochiral coiled coil

DOE PAGES

Mortenson, David E.; Steinkruger, Jay D.; Kreitler, Dale F.; ...

2015-10-12

Interactions between polypeptide chains containing amino acid residues with opposite absolute configurations have long been a source of interest and speculation, but there is very little structural information for such heterochiral associations. The need to address this lacuna has grown in recent years because of increasing interest in the use of peptides generated from D amino acids (D peptides) as specific ligands for natural proteins, e.g., to inhibit deleterious protein–protein interactions. Coiled–coil interactions, between or among α-helices, represent the most common tertiary and quaternary packing motif in proteins. Heterochiral coiled–coil interactions were predicted over 50 years ago by Crick, andmore » limited experimental data obtained in solution suggest that such interactions can indeed occur. To address the dearth of atomic-level structural characterization of heterochiral helix pairings, we report in this paper two independent crystal structures that elucidate coiled-coil packing between L- and D-peptide helices. Both structures resulted from racemic crystallization of a peptide corresponding to the transmembrane segment of the influenza M2 protein. Networks of canonical knobs-into-holes side-chain packing interactions are observed at each helical interface. Finally, however, the underlying patterns for these heterochiral coiled coils seem to deviate from the heptad sequence repeat that is characteristic of most homochiral analogs, with an apparent preference for a hendecad repeat pattern.« less

Localization of functional receptor epitopes on the structure of ciliary neurotrophic factor indicates a conserved, function-related epitope topography among helical cytokines.

PubMed

Panayotatos, N; Radziejewska, E; Acheson, A; Somogyi, R; Thadani, A; Hendrickson, W A; McDonald, N Q

1995-06-09

By rational mutagenesis, receptor-specific functional analysis, and visualization of complex formation in solution, we identified individual amino acid side chains involved specifically in the interaction of ciliary neurotrophic factor (CNTF) with CNTFR alpha and not with the beta-components, gp130 and LIFR. In the crystal structure, the side chains of these residues, which are located in helix A, the AB loop, helix B, and helix D, are surface accessible and are clustered in space, thus constituting an epitope for CNTFR alpha. By the same analysis, a partial epitope for gp130 was also identified on the surface of helix A that faces away from the alpha-epitope. Superposition of the CNTF and growth hormone structures showed that the location of these epitopes on CNTF is analogous to the location of the first and second receptor epitopes on the surface of growth hormone. Further comparison with proposed binding sites for alpha- and beta-receptors on interleukin-6 and leukemia inhibitory factor indicated that this epitope topology is conserved among helical cytokines. In each case, epitope I is utilized by the specificity-conferring component, whereas epitopes II and III are used by accessory components. Thus, in addition to a common fold, helical cytokines share a conserved order of receptor epitopes that is function related.

Structure, Function, Self-Assembly and Origin of Simple Membrane Proteins

NASA Technical Reports Server (NTRS)

Pohorille, Andrew

2003-01-01

Integral membrane proteins perform such essential cellular functions as transport of ions, nutrients and waste products across cell walls, transduction of environmental signals, regulation of cell fusion, recognition of other cells, energy capture and its conversion into high-energy compounds. In fact, 30-40% of genes in modem organisms codes for membrane proteins. Although contemporary membrane proteins or their functional assemblies can be quite complex, their transmembrane fragments are usually remarkably simple. The most common structural motif for these fragments is a bundle of alpha-helices, but occasionally it could be a beta-barrel. In a series of molecular dynamics computer simulations we investigated self-organizing properties of simple membrane proteins based on these structural motifs. Specifically, we studied folding and insertion into membranes of short, nonpolar or amphiphatic peptides. We also investigated glycophorin A, a peptide that forms sequence-specific dimers, and a transmembrane aggregate of four identical alpha-helices that forms an efficient and selective voltage-gated proton channel was investigated. Many peptides are attracted to water-membrane interfaces. Once at the interface, nonpolar peptides spontaneously fold to a-helices. Whenever the sequence permits, peptides that contain both polar and nonpolar amino also adopt helical structures, in which polar and nonpolar amino acid side chains are immersed in water and membrane, respectively. Specific identity of side chains is less important. Helical peptides at the interface could insert into the membrane and adopt a transmembrane conformation. However, insertion of a single helix is unfavorable because polar groups in the peptide become completely dehydrated upon insertion. The unfavorable free energy of insertion can be regained by spontaneous association of peptides in the membrane. The first step in this process is the formation of dimers, although the most common are aggregates of 4-7 helices. The helices could arrange themselves such that they formed pores capable of transporting ions and small molecules across membranes. Stability of transmembrane aggregates of simple proteins is often only marginal and, therefore, it can be regulated by environmental signals or small sequence modifications in the region of interhelical interactions. A key step in the earliest evolution of membrane proteins was the emergence of selectivity for specific substrates. Many channels could become selective if one or only a few properly chosen amino acids are properly placed along the channel, acting as filters or gates. This is a convenient evolutionary solution because it does not require imposing conditions on the whole sequence.

A Cobalt Supramolecular Triple-Stranded Helicate-based Discrete Molecular Cage

PubMed Central

Mai, Hien Duy; Kang, Philjae; Kim, Jin Kyung; Yoo, Hyojong

2017-01-01

We report a strategy to achieve a discrete cage molecule featuring a high level of structural hierarchy through a multiple-assembly process. A cobalt (Co) supramolecular triple-stranded helicate (Co-TSH)-based discrete molecular cage (1) is successfully synthesized and fully characterized. The solid-state structure of 1 shows that it is composed of six triple-stranded helicates interconnected by four linking cobalt species. This is an unusual example of a highly symmetric cage architecture resulting from the coordination-driven assembly of metallosupramolecular modules. The molecular cage 1 shows much higher CO2 uptake properties and selectivity compared with the separate supramolecular modules (Co-TSH, complex 2) and other molecular platforms. PMID:28262690

Helicity of a toroidal vortex with swirl

NASA Astrophysics Data System (ADS)

Bannikova, E. Yu.; Kontorovich, V. M.; Poslavsky, S. A.

2016-04-01

Based on the solutions of the Bragg-Hawthorne equation, we discuss the helicity of a thin toroidal vortex in the presence of swirl, orbital motion along the torus directrix. The relation between the helicity and circulations along the small and large linked circumferences (the torus directrix and generatrix) is shown to depend on the azimuthal velocity distribution in the core of the swirling ring vortex. In the case of nonuniform swirl, this relation differs from the well-known Moffat relation, viz., twice the product of such circulations multiplied by the number of linkages. The results can find applications in investigating the vortices in planetary atmospheres and the motions in the vicinity of active galactic nuclei.

Novel spin dynamics in ferrimagnetic molecular chains from 1H NMR and μSR spin-lattice relaxation measurements

NASA Astrophysics Data System (ADS)

Micotti, E.; Lascialfari, A.; Rigamonti, A.; Aldrovandi, S.; Caneschi, A.; Gatteschi, D.; Bogani, L.

2004-05-01

The spin dynamics in the helical chain Co(hfac) 2NITPhOMe has been investigated by 1H NMR and μSR relaxation. In the temperature range 15

Interaction of collagen with chlorosulphonated paraffin tanning agents: Fourier transform infrared spectroscopic analysis and molecular dynamics simulations.

PubMed

Monti, Susanna; Bramanti, Emilia; Della Porta, Valentina; Onor, Massimo; D'Ulivo, Alessandro; Barone, Vincenzo

2013-09-21

The binding of chlorosulphonated paraffins to collagen triple helices is studied by means of classical molecular dynamics simulations and experimental spectroscopic techniques in order to disclose the principal characteristics of their interaction during the leather fattening process. Indeed, collagen is the main target to develop new leather modifying agents with specific characteristics, and an accurate design of the collagen binders, supported by predictive computational strategies, could be a successful tool to obtain new effective eco-compatible compounds able to impart to the leather the required functionalities and distinctive mechanical properties. Possible effects caused by the tanning agents on the collagen matrix have been identified from both experimental and theoretical points of view. Computational data in agreement with experiment have revealed that chlorosulphonated paraffins can interact favorably with the collagen residues having amine groups in their side chains (Arg, Lys, Asn and Gln) and reduce the tendency of the solvated collagen matrix to swell. However, the interference of chlorosulphonated paraffins with the unfolding process, which is operated mainly by the action of water, can be due both to covalent cross-linking of the collagen chains and intermolecular hydrogen bonding interactions involving also the hydroxyl groups of Hyp, Ser and Thr residues.

Pyridinium cross-links in bone of patients with osteogenesis imperfecta: evidence of a normal intrafibrillar collagen packing.

PubMed

Bank, R A; Tekoppele, J M; Janus, G J; Wassen, M H; Pruijs, H E; Van der Sluijs, H A; Sakkers, R J

2000-07-01

The brittleness of bone in patients with osteogenesis imperfecta (OI) has been attributed to an aberrant collagen network. However, the role of collagen in the loss of tissue integrity has not been well established. To gain an insight into the biochemistry and structure of the collagen network, the cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) and the level of triple helical hydroxylysine (Hyl) were determined in bone of OI patients (types I, III, and IV) as well as controls. The amount of triple helical Hyl was increased in all patients. LP levels in OI were not significantly different; in contrast, the amount of HP (and as a consequence the HP/LP ratio and the total pyridinoline level) was significantly increased. There was no relationship between the sum of pyridinolines and the amount of triple helical Hyl, indicating that lysyl hydroxylation of the triple helix and the telopeptides are under separate control. Cross-linking is the result of a specific three-dimensional arrangement of collagens within the fibril; only molecules that are correctly aligned are able to form cross-links. Inasmuch as the total amount of pyridinoline cross-links in OI bone is similar to control bone, the packing geometry of intrafibrillar collagen molecules is not disturbed in OI. Consequently, the brittleness of bone is not caused by a disorganized intrafibrillar collagen packing and/or loss of cross-links. This is an unexpected finding, because mutant collagen molecules with a random distribution within the fibril are expected to result in disruptions of the alignment of neighboring collagen molecules. Pepsin digestion of OI bone revealed that collagen located at the surface of the fibril had lower cross-link levels compared with collagen located at the inside of the fibril, indicating that mutant molecules are not distributed randomly within the fibril but are located preferentially at the surface of the fibril.

Molecular Dynamics Simulation of Membranes and a Transmembrane Helix

NASA Astrophysics Data System (ADS)

Duong, Tap Ha; Mehler, Ernest L.; Weinstein, Harel

1999-05-01

Three molecular dynamics (MD) simulations of 1.5-ns length were carried out on fully hydrated patches of dimyristoyl phosphatidylcholine (DMPC) bilayers in the liquid-crystalline phase. The simulations were performed using different ensembles and electrostatic conditions: a microcanonical ensemble or constant pressure-temperature ensemble, with or without truncated electrostatic interactions. Calculated properties of the membrane patches from the three different protocols were compared to available data from experiments. These data include the resulting overall geometrical dimensions, the order characteristics of the lipid hydrocarbon chains, as well as various measures of the conformations of the polar head groups. The comparisons indicate that the simulation carried out within the microcanonical ensemble with truncated electrostatic interactions yielded results closest to the experimental data, provided that the initial equilibration phase preceding the production run was sufficiently long. The effects of embedding a non-ideal helical protein domain in the membrane patch were studied with the same MD protocols. This simulation was carried out for 2.5 ns. The protein domain corresponds to the seventh transmembrane segment (TMS7) of the human serotonin 5HT 2Areceptor. The peptide is composed of two α-helical segments linked by a hinge domain around a perturbing Asn-Pro motif that produces at the end of the simulation a kink angle of nearly 80° between the two helices. Several aspects of the TMS7 structure, such as the bending angle, backbone Φ and Ψ torsion angles, the intramolecular hydrogen bonds, and the overall conformation, were found to be very similar to those determined by NMR for the corresponding transmembrane segment of the tachykinin NK-1 receptor. In general, the simulations were found to yield structural and dynamic characteristics that are in good agreement with experiment. These findings support the application of simulation methods to the study of the complex biomolecular systems at the membrane interface of cells.

Free energy landscapes of short peptide chains using adaptively biased molecular dynamics

NASA Astrophysics Data System (ADS)

Karpusenka, Vadzim; Babin, Volodymyr; Roland, Christopher; Sagui, Celeste

2009-03-01

We present the results of a computational study of the free energy landscapes of short polypeptide chains, as a function of several reaction coordinates meant to distinguish between several known types of helices. The free energy landscapes were calculated using the recently developed adaptively biased molecular dynamics method followed up with equilibrium ``umbrella correction'' runs. Specific polypeptides investigated include small chains of pure and mixed alanine, glutamate, leucine, lysine and methionine (all amino acids with strong helix-forming propensities), as well as glycine, proline(having a low helix forming propensities), tyrosine, serine and arginine. Our results are consistent with the existing experimental and other theoretical evidence.

Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S proteasome

PubMed Central

Saeki, Yasushi; Kudo, Tai; Sone, Takayuki; Kikuchi, Yoshiko; Yokosawa, Hideyoshi; Toh-e, Akio; Tanaka, Keiji

2009-01-01

Recruitment of substrates to the 26S proteasome usually requires covalent attachment of the Lys48-linked polyubiquitin chain. In contrast, modifications with the Lys63-linked polyubiquitin chain and/or monomeric ubiquitin are generally thought to function in proteasome-independent cellular processes. Nevertheless, the ubiquitin chain-type specificity for the proteasomal targeting is still poorly understood, especially in vivo. Using mass spectrometry, we found that Rsp5, a ubiquitin-ligase in budding yeast, catalyzes the formation of Lys63-linked ubiquitin chains in vitro. Interestingly, the 26S proteasome degraded well the Lys63-linked ubiquitinated substrate in vitro. To examine whether Lys63-linked ubiquitination serves in degradation in vivo, we investigated the ubiquitination of Mga2-p120, a substrate of Rsp5. The polyubiquitinated p120 contained relatively high levels of Lys63-linkages, and the Lys63-linked chains were sufficient for the proteasome-binding and subsequent p120-processing. In addition, Lys63-linked chains as well as Lys48-linked chains were detected in the 26S proteasome-bound polyubiquitinated proteins. These results raise the possibility that Lys63-linked ubiquitin chain also serves as a targeting signal for the 26S proteaseome in vivo. PMID:19153599

Investigating the role of GXXXG motifs in helical folding and self-association of plasticins, Gly/Leu-rich antimicrobial peptides.

PubMed

Carlier, Ludovic; Joanne, Pierre; Khemtémourian, Lucie; Lacombe, Claire; Nicolas, Pierre; El Amri, Chahrazade; Lequin, Olivier

2015-01-01

Plasticins (PTC) are dermaseptin-related antimicrobial peptides characterized by a large number of leucine and glycine residues arranged in GXXXG motifs that are often described to promote helix association within biological membranes. We report the structure and interaction properties of two plasticins, PTC-B1 from Phyllomedusa bicolor and a cationic analog of PTC-DA1 from Pachymedusa dacnicolor, which exhibit membrane-lytic activities on a broad range of microorganisms. Despite a high number of glycine, CD and NMR spectroscopy show that the two plasticins adopt mainly alpha-helical conformations in a wide variety of environments such as trifluoroethanol, detergent micelles and lipid vesicles. In DPC and SDS, plasticins adopt well-defined helices that lie parallel to the micelle surface, all glycine residues being located on the solvent-exposed face. Spectroscopic data and cross-linking experiments indicate that the GXXXG repeats in these amphipathic helices do not provide a strong oligomerization interface, suggesting a different role from GXXXG motifs found in transmembrane helices. Copyright © 2014 Elsevier B.V. All rights reserved.

NMR structural and dynamic characterization of the acid-unfolded state of apomyoglobin provides insights into the early events in protein folding.

PubMed

Yao, J; Chung, J; Eliezer, D; Wright, P E; Dyson, H J

2001-03-27

Apomyoglobin forms a denatured state under low-salt conditions at pH 2.3. The conformational propensities and polypeptide backbone dynamics of this state have been characterized by NMR. Nearly complete backbone and some side chain resonance assignments have been obtained, using a triple-resonance assignment strategy tailored to low protein concentration (0.2 mM) and poor chemical shift dispersion. An estimate of the population and location of residual secondary structure has been made by examining deviations of (13)C(alpha), (13)CO, and (1)H(alpha) chemical shifts from random coil values, scalar (3)J(HN,H)(alpha) coupling constants and (1)H-(1)H NOEs. Chemical shifts constitute a highly reliable indicator of secondary structural preferences, provided the appropriate random coil chemical shift references are used, but in the case of acid-unfolded apomyoglobin, (3)J(HN,H)(alpha) coupling constants are poor diagnostics of secondary structure formation. Substantial populations of helical structure, in dynamic equilibrium with unfolded states, are formed in regions corresponding to the A and H helices of the folded protein. In addition, the deviation of the chemical shifts from random coil values indicates the presence of helical structure encompassing the D helix and extending into the first turn of the E helix. The polypeptide backbone dynamics of acid-unfolded apomyoglobin have been investigated using reduced spectral density function analysis of (15)N relaxation data. The spectral density J(omega(N)) is particularly sensitive to variations in backbone fluctuations on the picosecond to nanosecond time scale. The central region of the polypeptide spanning the C-terminal half of the E helix, the EF turn, and the F helix behaves as a free-flight random coil chain, but there is evidence from J(omega(N)) of restricted motions on the picosecond to nanosecond time scale in the A and H helix regions where there is a propensity to populate helical secondary structure in the acid-unfolded state. Backbone fluctuations are also restricted in parts of the B and G helices due to formation of local hydrophobic clusters. Regions of restricted backbone flexibility are generally associated with large buried surface area. A significant increase in J(0) is observed for the NH resonances of some residues located in the A and G helices of the folded protein and is associated with fluctuations on a microsecond to millisecond time scale that probably arise from transient contacts between these distant regions of the polypeptide chain. Our results indicate that the equilibrium unfolded state of apomyoglobin formed at pH 2.3 is an excellent model for the events that are expected to occur in the earliest stages of protein folding, providing insights into the regions of the polypeptide that spontaneously undergo local hydrophobic collapse and sample nativelike secondary structure.

Configuration of the magnetosome chain: a natural magnetic nanoarchitecture.

PubMed

Orue, I; Marcano, L; Bender, P; García-Prieto, A; Valencia, S; Mawass, M A; Gil-Cartón, D; Alba Venero, D; Honecker, D; García-Arribas, A; Fernández Barquín, L; Muela, A; Fdez-Gubieda, M L

2018-04-26

Magnetospirillum gryphiswaldense is a microorganism with the ability to biomineralize magnetite nanoparticles, called magnetosomes, and arrange them into a chain that behaves like a magnetic compass. Rather than straight lines, magnetosome chains are slightly bent, as evidenced by electron cryotomography. Our experimental and theoretical results suggest that due to the competition between the magnetocrystalline and shape anisotropies, the effective magnetic moment of individual magnetosomes is tilted out of the [111] crystallographic easy axis of magnetite. This tilt does not affect the direction of the chain net magnetic moment, which remains along the [111] axis, but explains the arrangement of magnetosomes in helical-like shaped chains. Indeed, we demonstrate that the chain shape can be reproduced by considering an interplay between the magnetic dipolar interactions between magnetosomes, ruled by the orientation of the magnetosome magnetic moment, and a lipid/protein-based mechanism, modeled as an elastic recovery force exerted on the magnetosomes.

Mouse interleukin-2 structure-function studies: substitutions in the first alpha-helix can specifically inactivate p70 receptor binding and mutations in the fifth alpha-helix can specifically inactivate p55 receptor binding.

PubMed Central

Zurawski, S M; Zurawski, G

1989-01-01

The function of two alpha-helical regions of mouse interleukin-2 were analyzed by saturation substitution analysis. The functional parts of the first alpha-helix (A) was defined as residues 31-39 by the observation that proline substitutions within this region inactivate the protein. Four residues within alpha-helix A, Leu31, Asp34, Leu35 and Leu38, were found to be crucial for biological activity. Structural modeling suggested that these four residues are clustered on one face of alpha-helix A. Residues 31 and 35 had to remain hydrophobic for the molecule to be functional. At residue 38 there was a preference for hydrophobic side chain residues, while at residue 34 some small side chain residues as well as acidic or amide side chain residues were functionally acceptable. Inactivating changes at residue 34 had no effect upon the ability of the protein to interact with the p55 receptor. Disruption of the fifth alpha-helix (E), which had little effect upon biological activity, resulted in an inability of the protein to interact with the p55 receptor. Mutagenesis of the alpha-helix E region demonstrated that alpha-helicity and the nature of the side chain residues in this region were unimportant for biological activity. The region immediately proximal to alpha-helix E was important only for the single intramolecular disulfide linkage. PMID:2583124

Impact on molecular organization of amylopectin in starch granules upon annealing.

PubMed

Vamadevan, Varatharajan; Bertoft, Eric; Soldatov, Dmitriy V; Seetharaman, Koushik

2013-10-15

This study investigated the influence of the internal structure of amylopectin on annealing (3h, 24h) of starches from four different types of amylopectin (Bertoft, Koch, & Aman, 2012; Bertoft, Piyachomkwan, Chatakanonda, & Sriroth, 2008). Regardless of the starch source and incubation time, annealing significantly increased the onset gelatinization temperature (To) and narrowed and deepened the amylopectin endotherm. However, the extent of the change in the melting temperature (Tm) and the enthalpy of gelatinization (ΔH) differed among the types. In terms of the To and Tm, starches from type 1 (oat, rye, barley, and waxy barley) showed the most significant response to annealing. The Tm of starches belonging to type 2 (waxy maize, rice, waxy rice, and sago) remained unchanged after 3h of annealing. Type 1 and type 2 starches with the lowest gelatinization temperatures showed the greatest increase in melting temperature after annealing. However, type 3 (tapioca, mung bean, and arrowroot) and type 4 (potato, waxy potato, canna, and yam) starches were not in line with these observations. Instead, starches from type 3 and type 4 showed a pronounced increase in the ΔH. The inter-block chain length (IB-CL) (distance between tightly branched units within a cluster) correlated positively (r=0.93, p<0.01) with the change in enthalpy after 24h of annealing. These data indicate that a short IB-CL affects the optimum registration of double helices within the crystalline lamellae. The relationship between the gelatinization parameters before and after annealing suggests that type 1 and 2 starches might possess a high number of unpacked double helices (type 1>type 2) compared to other types. Longer IB-CLs, which facilitate the parallel packing of splayed double helices, and the lengthening of double helices likely increased the ΔH in type 3 and type 4 starches. It is concluded that annealing can be used as a probe for visualizing the organization of glucan chains (alignment of double helices/degree of perfection) within crystalline lamellae. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dioleoyl-phosphatidic acid selectively binds to α-synuclein and strongly induces its aggregation.

PubMed

Mizuno, Satoru; Sasai, Hirotaka; Kume, Aiko; Takahashi, Daisuke; Satoh, Mamoru; Kado, Sayaka; Sakane, Fumio

2017-03-01

α-Synuclein (α-syn), which causally links to Parkinson's disease, binds to vesicles containing phosphatidic acid (PA). However, the effects of the fatty acyl chains of PA on its ability to bind to α-syn protein remain unclear. Intriguingly, we reveal that among several PA species, 18:1/18:1-PA is the most strongly bound PA to the α-syn protein. Moreover, 18:1/18:1-PA more strongly enhances secondary structural changes from the random coil form to the α-helical form than 16:0/18:1-PA. Furthermore, 18:1/18:1-PA more markedly accelerates generation of multimeric and proteinase K-resistant α-syn protein compared to 16:0/18:1-PA. These results indicate that among phospholipids examined so far, 18:1/18:1-PA demonstrates the strongest binding to α-syn, as well as the most effective enhancement of its secondary structural changes and aggregation formation. © 2017 Federation of European Biochemical Societies.

Physical-chemical studies of proteins of squid nerve axoplasm, with special reference to the axon fibrous protein.

PubMed

DAVISON, P F; TAYLOR, E W

1960-03-01

The proteins in the axoplasm of the squid, Dosidicus gigas, have been resolved electrophoretically into a major fraction including the fibrous protein, and possibly its structural subunits, and a minor fraction including at least two proteins with low sedimentation coefficients. A partially reversible change in the structure of the fibrous protein occurs under the action of 0.4 M salt or high pH. These experiments have been interpreted to indicate that in the intact fiber one, or a few, protofibrils are arranged helically or longitudinally along the fiber axis, and linked by electrostatic bonds. On the dissociation of these bonds the separated protofibrils assume a less extended form and sediment more rapidly than the intact fibers. Some material with a lower sedimentation rate is also released on the dissociation. This fraction may comprise smaller chain fragments. The volume fraction and the approximate refractive index of the fibers have been calculated.

Physical-Chemical Studies of Proteins of Squid Nerve Axoplasm, with Special Reference to the Axon Fibrous Protein

PubMed Central

Davison, Peter F.; Taylor, Edwin W.

1960-01-01

The proteins in the axoplasm of the squid, Dosidicus gigas, have been resolved electrophoretically into a major fraction including the fibrous protein, and possibly its structural subunits, and a minor fraction including at least two proteins with low sedimentation coefficients. A partially reversible change in the structure of the fibrous protein occurs under the action of 0.4 M salt or high pH. These experiments have been interpreted to indicate that in the intact fiber one, or a few, protofibrils are arranged helically or longitudinally along the fiber axis, and linked by electrostatic bonds. On the dissociation of these bonds the separated protofibrils assume a less extended form and sediment more rapidly than the intact fibers. Some material with a lower sedimentation rate is also released on the dissociation. This fraction may comprise smaller chain fragments. The volume fraction and the approximate refractive index of the fibers have been calculated. PMID:13814536

Fifty years of coiled-coils and alpha-helical bundles: a close relationship between sequence and structure.

PubMed

Parry, David A D; Fraser, R D Bruce; Squire, John M

2008-09-01

alpha-Helical coiled coils are remarkable for the diversity of related conformations that they adopt in both fibrous and globular proteins, and for the range of functions that they exhibit. The coiled coils are based on a heptad (7-residue), hendecad (11-residue) or a related quasi-repeat of apolar residues in the sequences of the alpha-helical regions involved. Most of these, however, display one or more sequence discontinuities known as stutters or stammers. The resulting coiled coils vary in length, in the number of chains participating, in the relative polarity of the contributing alpha-helical regions (parallel or antiparallel), and in the pitch length and handedness of the supercoil (left- or right-handed). Functionally, the concept that a coiled coil can act only as a static rod is no longer valid, and the range of roles that these structures have now been shown to exhibit has expanded rapidly in recent years. An important development has been the recognition that the delightful simplicity that exists between sequence and structure, and between structure and function, allows coiled coils with specialized features to be designed de novo.

Helix-packing motifs in membrane proteins.

PubMed

Walters, R F S; DeGrado, W F

2006-09-12

The fold of a helical membrane protein is largely determined by interactions between membrane-imbedded helices. To elucidate recurring helix-helix interaction motifs, we dissected the crystallographic structures of membrane proteins into a library of interacting helical pairs. The pairs were clustered according to their three-dimensional similarity (rmsd

Conformational and orientational order and disorder in solid polytetrafluoroethylene

NASA Astrophysics Data System (ADS)

Sprik, Michiel; Rothlisberger, Ursula; Klein, Michael L.

The low pressure phase diagram of solid polytetrafluoroethylene (PTFE/Teflon) has been investigated using constant temperature-constant pressure molecular dynamics techniques and a new all-atom potential model for fluorocarbons. The simulation was started in an ordered low temperature phase in which the molecules are parallel and have a helical conformation with a pitch of uniform magnitude and sign (chirality). In accordance with experiment, a transition to an orientationally disordered state is observed upon heating. The coherent helical winding of CF2 groups also disappears abruptly at the transition but short helical segments remain and become equally distributed between left and right chirality with increasing temperature. The orientational and conformational disorder is accompanied by translational diffusion along the chain direction. At a still higher temperature melting sets in. On cooling, the disordered solid phase is recovered and its structure is shown to be identical to that generated on heating. On further cooling, a spontaneous ordering transition is observed but the system fails to recover a uniform helical ground state. Instead, the high pressure ordered monoclinic all- trans (alkane-like) structure is obtained: an observation that indicates a deficiency in the potential model.

Photoreactive Stapled BH3 Peptides to Dissect the BCL-2 Family Interactome

PubMed Central

Braun, Craig R.; Mintseris, Julian; Gavathiotis, Evripidis; Bird, Gregory H.; Gygi, Steven P.; Walensky, Loren D.

2010-01-01

SUMMARY Defining protein interactions forms the basis for discovery of biological pathways, disease mechanisms, and opportunities for therapeutic intervention. To harness the robust binding affinity and selectivity of structured peptides for interactome discovery, we engineered photoreactive stapled BH3 peptide helices that covalently capture their physiologic BCL-2 family targets. The crosslinking α-helices covalently trap both static and dynamic protein interactors, and enable rapid identification of interaction sites, providing a critical link between interactome discovery and targeted drug design. PMID:21168768

Decay of helical and nonhelical magnetic knots

NASA Astrophysics Data System (ADS)

Candelaresi, Simon; Brandenburg, Axel

2011-07-01

We present calculations of the relaxation of magnetic field structures that have the shape of particular knots and links. A set of helical magnetic flux configurations is considered, which we call n-foil knots of which the trefoil knot is the most primitive member. We also consider two nonhelical knots; namely, the Borromean rings as well as a single interlocked flux rope that also serves as the logo of the Inter-University Centre for Astronomy and Astrophysics in Pune, India. The field decay characteristics of both configurations is investigated and compared with previous calculations of helical and nonhelical triple-ring configurations. Unlike earlier nonhelical configurations, the present ones cannot trivially be reduced via flux annihilation to a single ring. For the n-foil knots the decay is described by power laws that range form t-2/3 to t-1/3, which can be as slow as the t-1/3 behavior for helical triple-ring structures that were seen in earlier work. The two nonhelical configurations decay like t-1, which is somewhat slower than the previously obtained t-3/2 behavior in the decay of interlocked rings with zero magnetic helicity. We attribute the difference to the creation of local structures that contain magnetic helicity which inhibits the field decay due to the existence of a lower bound imposed by the realizability condition. We show that net magnetic helicity can be produced resistively as a result of a slight imbalance between mutually canceling helical pieces as they are being driven apart. We speculate that higher order topological invariants beyond magnetic helicity may also be responsible for slowing down the decay of the two more complicated nonhelical structures mentioned above.

Cooperative alpha-helix formation of beta-lactoglobulin induced by sodium n-alkyl sulfates.

PubMed

Chamani, J; Moosavi-Movahedi, A A; Rajabi, O; Gharanfoli, M; Momen-Heravi, M; Hakimelahi, G H; Neamati-Baghsiah, A; Varasteh, A R

2006-01-01

It is generally assumed that folding intermediates contain partially formed native-like secondary structures. However, if we consider the fact that the conformational stability of the intermediate state is simpler than that of the native state, it would be expected that the secondary structures in a folding intermediate would not necessarily be similar to those of the native state. beta-Lactoglobulin is a predominantly beta-sheet protein, although it has a markedly high intrinsic preference for alpha-helical structure. The formation of non-native alpha-helical intermediate of beta-lactoglobulin was induced by n-alkyl sulfates including sodium octyl sulfate, SOS; sodium decyl sulfate, SDeS; sodium dodecyl sulfate, SDS; and sodium tetradecyl sulfate, STS at special condition. The effect of n-alkyl sulfates on the structure of native beta-lactoglobulin at pH 2 was utilized to investigate the contribution of hydrophobic interactions to the stability of non-native alpha-helical intermediate. The addition of various concentrations of n-alkyl sulfates to the native state of beta-lactoglobulin (pH 2) appears to support the stabilized form of non-native alpha-helical intermediate at pH 2. The m values of the intermediate state of beta-lactoglobulin by SOS, SDeS, SDS and STS showed substantial variation. The enhancement of m values as the stability criterion of non-native alpha-helical intermediate state corresponded with increasing chain length of the cited n-alkyl sulfates. The present results suggest that the folding reaction of beta-lactoglobulin follows a non-hierarchical mechanism and hydrophobic interactions play important roles in stabilizing the non-native alpha-helical intermediate state.

Infrared and Raman spectroscopy and quantum chemistry calculation studies of C H⋯O hydrogen bondings and thermal behavior of biodegradable polyhydroxyalkanoate

NASA Astrophysics Data System (ADS)

Sato, Harumi; Dybal, Jiří; Murakami, Rumi; Noda, Isao; Ozaki, Yukihiro

2005-06-01

This review paper reports infrared (IR) and Raman spectroscopy and quantum chemistry calculation studies of C-H⋯O hydrogen bondings and thermal behavior of biodegradable polyhydroxyalkanoates. IR and Raman spectra were measured for poly(3-hydroxybutyrate) (PHB) and a new type of bacterial copolyester, poly(3-hydroxybutyrate- co-3-hydroxyhexanoate), P(HB- co-HHx) (HHx=12 mol%) over a temperature range of 20 °C to higher temperatures (PHB, 200 °C; HHx=12 mol%, 140 °C) to explore their structure and thermal behavior. One of bands due to the CH 3 asymmetric stretching modes appears near 3010 cm -1 in the IR and Raman spectra of PHB and P(HB- co-HHx) at 20 °C. These frequencies of IR and Raman CH 3 asymmetric stretching bands are much higher than usual. These anomalous frequencies of the CH 3 asymmetric stretching bands together with the X-ray crystallographic structure of PHB have suggested that there is an inter- or intra-molecular C-H⋯O hydrogen bond between the C dbnd6 O group in one helical structure and the CH 3 group in the other helical structure in PHB and P(HB- co-HHx). The quantum chemical calculation of model compounds of PHB also has suggested the existence of C-H⋯O hydrogen bonds in PHB and P(HB- co-HHx). It is very likely that a chain of C-H⋯O hydrogen bond pairs link two parallel helical structures in the crystalline parts. The temperature-dependent IR and Raman spectral variations have revealed that the crystallinity of P(HB- co-HHx) (HHx=12 mol%) decreases gradually from a fairly low temperature (about 60 °C), while the crystallinity of PHB remains almost unchanged until just below its melting temperature. It has also been found from the IR and Raman studies that for both PHB and P(HB- co-HHx) the weakening of the C-H⋯O hydrogen bonds starts from just above room temperature, but the deformation of helical structures occurs after the weakening of the C-H⋯O hydrogen bonds advances to some extent.

Evidence That GH115 α-Glucuronidase Activity, Which Is Required to Degrade Plant Biomass, Is Dependent on Conformational Flexibility*

PubMed Central

Rogowski, Artur; Baslé, Arnaud; Farinas, Cristiane S.; Solovyova, Alexandra; Mortimer, Jennifer C.; Dupree, Paul; Gilbert, Harry J.; Bolam, David N.

2014-01-01

The microbial degradation of the plant cell wall is an important biological process that is highly relevant to environmentally significant industries such as the bioenergy and biorefining sectors. A major component of the wall is glucuronoxylan, a β1,4-linked xylose polysaccharide that is decorated with α-linked glucuronic and/or methylglucuronic acid (GlcA/MeGlcA). Recently three members of a glycoside hydrolase family, GH115, were shown to hydrolyze MeGlcA side chains from the internal regions of xylan, an activity that has not previously been described. Here we show that a dominant member of the human microbiota, Bacteroides ovatus, contains a GH115 enzyme, BoAgu115A, which displays glucuronoxylan α-(4-O-methyl)-glucuronidase activity. The enzyme is significantly more active against substrates in which the xylose decorated with GlcA/MeGlcA is flanked by one or more xylose residues. The crystal structure of BoAgu115A revealed a four-domain protein in which the active site, comprising a pocket that abuts a cleft-like structure, is housed in the second domain that adopts a TIM barrel-fold. The third domain, a five-helical bundle, and the C-terminal β-sandwich domain make inter-chain contacts leading to protein dimerization. Informed by the structure of the enzyme in complex with GlcA in its open ring form, in conjunction with mutagenesis studies, the potential substrate binding and catalytically significant amino acids were identified. Based on the catalytic importance of residues located on a highly flexible loop, the enzyme is required to undergo a substantial conformational change to form a productive Michaelis complex with glucuronoxylan. PMID:24214982

Comprehensive analysis of all triple helical repeats in beta-spectrins reveals patterns of selective evolutionary conservation.

PubMed

Baines, Anthony J

2003-01-01

The spectrin superfamily (spectrin, alpha-actinin, utrophin and dystrophin) has in common a triple helical repeating unit of ~106 amino acid residues. In spectrin, alpha and beta chains contain multiple copies of this repeat. beta-spectrin chains contain the majority of binding activities in spectrin and are essential for animal life. Canonical beta-spectrins have 17 repeats; beta-heavy spectrins have 30. Here, the repeats of five human beta-spectrins, plus beta-spectrins from several other vertebrates and invertebrates, have been analysed. Repeats 1, 2, 14 and 17 in canonical beta are highly conserved between invertebrates and vertebrates, and repeat 8 in some isoforms. This is consistent with conservation of critical functions, since repeats 1, 2 and 17 bind alpha-spectrin. Repeats 1 of beta-spectrins are not always detected by SMART or Pfam tools. A profile hidden Markov model of beta-spectrin repeat 1 detects alpha-actinins, but not utrophin or dystrophin. Novel examples of repeat 1 were detected in the spectraplakins MACF1, BPAG1 and plectin close to the actin-binding domain. Ankyrin binds to the C-terminal portion of repeat 14; the high conservation of this entire repeat may point to additional, undiscovered ligand-binding activities. This analysis indicates that the basic triple helical repeat pattern was adapted early in the evolution of the spectrin superfamily to encompass essential binding activities, which characterise individual repeats in proteins extant today.

Biomolecular dynamics studied with IR-spectroscopy using quantum cascade lasers combined with nanosecond perturbation techniques

NASA Astrophysics Data System (ADS)

Popp, Alexander; Scheerer, David; Heck, Benjamin; Hauser, Karin

2017-06-01

Early events of protein folding can be studied with fast perturbation techniques triggering non-equilibrium relaxation dynamics. A nanosecond laser-excited pH-jump or temperature-jump (T-jump) was applied to initiate helix folding or unfolding of poly-L-glutamic acid (PGA). PGA is a homopolypeptide with titratable carboxyl side-chains whose protonation degree determines the PGA conformation. A pH-jump was realized by the photochemical release of protons and induces PGA folding due to protonation of the side-chains. Otherwise, the helical conformation can be unfolded by a T-jump. We operated under conditions where PGA does not aggregate and temperature and pH are the regulatory properties of its conformation. The experiments were performed in such a manner that the folding/unfolding jump proceeded to the same PGA conformation. We quantified the increase/decrease in helicity induced by the pH-/T-jump and demonstrated that the T-jump results in a relatively small change in helical content in contrast to the pH-jump. This is caused by the strong pH-dependence of the PGA conformation. The conformational changes were detected by time-resolved single wavelength IR-spectroscopy using quantum cascade lasers (QCL). We could independently observe the kinetics for α-helix folding and unfolding in PGA by using different perturbation techniques and demonstrate the high sensitivity of time-resolved IR-spectroscopy to study protein folding mechanisms.

Biomolecular dynamics studied with IR-spectroscopy using quantum cascade lasers combined with nanosecond perturbation techniques.

PubMed

Popp, Alexander; Scheerer, David; Heck, Benjamin; Hauser, Karin

2017-06-15

Early events of protein folding can be studied with fast perturbation techniques triggering non-equilibrium relaxation dynamics. A nanosecond laser-excited pH-jump or temperature-jump (T-jump) was applied to initiate helix folding or unfolding of poly-l-glutamic acid (PGA). PGA is a homopolypeptide with titratable carboxyl side-chains whose protonation degree determines the PGA conformation. A pH-jump was realized by the photochemical release of protons and induces PGA folding due to protonation of the side-chains. Otherwise, the helical conformation can be unfolded by a T-jump. We operated under conditions where PGA does not aggregate and temperature and pH are the regulatory properties of its conformation. The experiments were performed in such a manner that the folding/unfolding jump proceeded to the same PGA conformation. We quantified the increase/decrease in helicity induced by the pH-/T-jump and demonstrated that the T-jump results in a relatively small change in helical content in contrast to the pH-jump. This is caused by the strong pH-dependence of the PGA conformation. The conformational changes were detected by time-resolved single wavelength IR-spectroscopy using quantum cascade lasers (QCL). We could independently observe the kinetics for α-helix folding and unfolding in PGA by using different perturbation techniques and demonstrate the high sensitivity of time-resolved IR-spectroscopy to study protein folding mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Engineering one-dimensional topological phases on p -wave superconductors

NASA Astrophysics Data System (ADS)

Sahlberg, Isac; Westström, Alex; Pöyhönen, Kim; Ojanen, Teemu

2017-05-01

In this paper, we study how, with the aid of impurity engineering, two-dimensional p -wave superconductors can be employed as a platform for one-dimensional topological phases. We discover that, while chiral and helical parent states themselves are topologically nontrivial, a chain of scalar impurities on both systems supports multiple topological phases and Majorana end states. We develop an approach which allows us to extract the topological invariants and subgap spectrum, even away from the center of the gap, for the representative cases of spinless, chiral, and helical superconductors. We find that the magnitude of the topological gaps protecting the nontrivial phases may be a significant fraction of the gap of the underlying superconductor.

Reduced viscosity for flagella moving in a solution of long polymer chains

NASA Astrophysics Data System (ADS)

Zhang, Yuchen; Li, Gaojin; Ardekani, Arezoo M.

2018-02-01

The bacterial flagellum thickness is smaller than the radius of gyration of long polymer chain molecules. The flow velocity gradient over the length of polymer chains can be nonuniform and continuum models of polymeric liquids break in this limit. In this work, we use Brownian dynamics simulations to study a rotating helical flagellum in a polymer solution and overcome this limitation. As the polymer size increases, the viscosity experienced by the flagellum asymptotically reduces to the solvent viscosity. The contribution of polymer molecules to the local viscosity in a solution of long polymer chains decreases with the inverse of polymer size to the power 1/2. The difference in viscosity experienced by the bacterial cell body and flagella can predict the nonmonotonic swimming speed of bacteria in polymer solutions.

Structural stability of proteins in aqueous and nonpolar environments

NASA Astrophysics Data System (ADS)

Yasuda, Satoshi; Oshima, Hiraku; Kinoshita, Masahiro

2012-10-01

A protein folds into its native structure with the α-helix and/or β-sheet in aqueous solution under the physiological condition. The relative content of these secondary structures largely varies from protein to protein. However, such structural variability is not exhibited in nonaqueous environment. For example, there is a strong trend that alcohol induces a protein to form α-helices, and many of the membrane proteins within the lipid bilayer consists of α-helices. Here we investigate the structural stability of proteins in aqueous and nonpolar environments using our recently developed free-energy function F = (Λ - TS)/(kBT0) = Λ/(kBT0) - S/kB (T0 = 298 K and the absolute temperature T is set at T0) which is based on statistical thermodynamics. Λ/(kBT0) and S/kB are the energetic and entropic components, respectively, and kB is Boltzmann's constant. A smaller value of the positive quantity, -S, represents higher efficiency of the backbone and side-chain packing promoted by the entropic effect arising from the translational displacement of solvent molecules or the CH2, CH3, and CH groups which constitute nonpolar chains of lipid molecules. As for Λ, in aqueous solution, a transition to a more compact structure of a protein accompanies the break of protein-solvent hydrogen bonds: As the number of donors and acceptors buried without protein intramolecular hydrogen bonding increases, Λ becomes higher. In nonpolar solvent, lower Λ simply implies more intramolecular hydrogen bonds formed. We find the following. The α-helix and β-sheet are advantageous with respect to -S as well as Λ and to be formed as much as possible. In aqueous solution, the solvent-entropy effect on the structural stability is so strong that the close packing of side chains is dominantly important, and the α-helix and β-sheet contents are judiciously adjusted to accomplish it. In nonpolar solvent, the solvent-entropy effect is substantially weaker than in aqueous solution. Λ is crucial and the α-helix is more stable than the β-sheet in terms of Λ, which develops a tendency that α-helices are exclusively chosen. For a membrane protein, α-helices are stabilized as fundamental structural units for the same reason, but their arrangement is performed through the entropic effect mentioned above.

Amylose-dicarboxylic acid inclusion complexes: Characterization and comparison to monocarboxylic acid complexes

USDA-ARS?s Scientific Manuscript database

One of the main components in starch, amylose is an essentially linear polymer composed of glucose connected through alpha-1,4-bonds. Amylose is well known to form helical inclusion complexes with various types of ligands such as iodine, medium and long chain fatty acids, alcohols, lactones, and fl...

Entropic (de)stabilization of surface-bound peptides conjugated with polymers

NASA Astrophysics Data System (ADS)

Carmichael, Scott P.; Shell, M. Scott

2015-12-01

In many emerging biotechnologies, functional proteins must maintain their native structures on or near interfaces (e.g., tethered peptide arrays, protein coated nanoparticles, and amphiphilic peptide micelles). Because the presence of a surface is known to dramatically alter the thermostability of tethered proteins, strategies to stabilize surface-bound proteins are highly sought. Here, we show that polymer conjugation allows for significant control over the secondary structure and thermostability of a model surface-tethered peptide. We use molecular dynamics simulations to examine the folding behavior of a coarse-grained helical peptide that is conjugated to polymers of various lengths and at various conjugation sites. These polymer variations reveal surprisingly diverse behavior, with some stabilizing and some destabilizing the native helical fold. We show that ideal-chain polymer entropies explain these varied effects and can quantitatively predict shifts in folding temperature. We then develop a generic theoretical model, based on ideal-chain entropies, that predicts critical lengths for conjugated polymers to effect changes in the folding of a surface-bound protein. These results may inform new design strategies for the stabilization of surface-associated proteins important for a range technological applications.

Bilinear forms and soliton solutions for a fourth-order variable-coefficient nonlinear Schrödinger equation in an inhomogeneous Heisenberg ferromagnetic spin chain or an alpha helical protein

NASA Astrophysics Data System (ADS)

Yang, Jin-Wei; Gao, Yi-Tian; Wang, Qi-Min; Su, Chuan-Qi; Feng, Yu-Jie; Yu, Xin

2016-01-01

In this paper, a fourth-order variable-coefficient nonlinear Schrödinger equation is studied, which might describe a one-dimensional continuum anisotropic Heisenberg ferromagnetic spin chain with the octuple-dipole interaction or an alpha helical protein with higher-order excitations and interactions under continuum approximation. With the aid of auxiliary function, we derive the bilinear forms and corresponding constraints on the variable coefficients. Via the symbolic computation, we obtain the Lax pair, infinitely many conservation laws, one-, two- and three-soliton solutions. We discuss the influence of the variable coefficients on the solitons. With different choices of the variable coefficients, we obtain the parabolic, cubic, and periodic solitons, respectively. We analyse the head-on and overtaking interactions between/among the two and three solitons. Interactions between a bound state and a single soliton are displayed with different choices of variable coefficients. We also derive the quasi-periodic formulae for the three cases of the bound states.

Entropic (de)stabilization of surface-bound peptides conjugated with polymers.

PubMed

Carmichael, Scott P; Shell, M Scott

2015-12-28

In many emerging biotechnologies, functional proteins must maintain their native structures on or near interfaces (e.g., tethered peptide arrays, protein coated nanoparticles, and amphiphilic peptide micelles). Because the presence of a surface is known to dramatically alter the thermostability of tethered proteins, strategies to stabilize surface-bound proteins are highly sought. Here, we show that polymer conjugation allows for significant control over the secondary structure and thermostability of a model surface-tethered peptide. We use molecular dynamics simulations to examine the folding behavior of a coarse-grained helical peptide that is conjugated to polymers of various lengths and at various conjugation sites. These polymer variations reveal surprisingly diverse behavior, with some stabilizing and some destabilizing the native helical fold. We show that ideal-chain polymer entropies explain these varied effects and can quantitatively predict shifts in folding temperature. We then develop a generic theoretical model, based on ideal-chain entropies, that predicts critical lengths for conjugated polymers to effect changes in the folding of a surface-bound protein. These results may inform new design strategies for the stabilization of surface-associated proteins important for a range technological applications.

Crystal Structure of FadA Adhesin from Fusobacterium nucleatum Reveals a Novel Oligomerization Motif, the Leucine Chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nithianantham, Stanley; Xu, Minghua; Yamada, Mitsunori

2009-04-07

Many bacterial appendages have filamentous structures, often composed of repeating monomers assembled in a head-to-tail manner. The mechanisms of such linkages vary. We report here a novel protein oligomerization motif identified in the FadA adhesin from the Gram-negative bacterium Fusobacterium nucleatum. The 2.0 {angstrom} crystal structure of the secreted form of FadA (mFadA) reveals two antiparallel {alpha}-helices connected by an intervening 8-residue hairpin loop. Leucine-leucine contacts play a prominent dual intra- and intermolecular role in the structure and function of FadA. First, they comprise the main association between the two helical arms of the monomer; second, they mediate the head-to-tailmore » association of monomers to form the elongated polymers. This leucine-mediated filamentous assembly of FadA molecules constitutes a novel structural motif termed the 'leucine chain.' The essential role of these residues in FadA is corroborated by mutagenesis of selected leucine residues, which leads to the abrogation of oligomerization, filament formation, and binding to host cells.« less

The Structural Basis for Matrix Metalloproteinase 1 Catalyzed Collagenolysis

PubMed Central

Bertini, Ivano; Fragai, Marco; Luchinat, Claudio; Melikian, Maxime; Toccafondi, Mirco; Lauer, Janelle L.; Fields, Gregg B.

2012-01-01

The proteolysis of collagen triple-helical structure (collagenolysis) is a poorly understood yet critical physiological process. Presently, matrix metalloproteinase 1 (MMP-1) and collagen triple-helical peptide models have been utilized to characterize the events and calculate the energetics of collagenolysis via NMR spectroscopic analysis of 12 enzyme-substrate complexes. The triple-helix is bound initially by the MMP-1 hemopexin-like (HPX) domain via a four amino acid stretch (analogous to type I collagen residues 782–785). The triple-helix is then presented to the MMP-1 catalytic (CAT) domain in a distinct orientation. The HPX and CAT domains are rotated with respect to one another compared with the X-ray “closed” conformation of MMP-1. Back-rotation of the CAT and HPX domains to the X-ray closed conformation releases one chain out of the triple-helix, and this chain is properly positioned in the CAT domain active site for subsequent hydrolysis. The aforementioned steps provide a detailed, experimentally-derived, and energetically favorable collagenolytic mechanism, as well as significant insight into the roles of distinct domains in extracellular protease function. PMID:22239621

Huntingtin interacting protein 1 (HIP1) regulates clathrin assembly through direct binding to the regulatory region of the clathrin light chain.

PubMed

Legendre-Guillemin, Valerie; Metzler, Martina; Lemaire, Jean-Francois; Philie, Jacynthe; Gan, Lu; Hayden, Michael R; McPherson, Peter S

2005-02-18

Huntingtin interacting protein 1 (HIP1) is a component of clathrin coats. We previously demonstrated that HIP1 promotes clathrin assembly through its central helical domain, which binds directly to clathrin light chains (CLCs). To better understand the relationship between CLC binding and clathrin assembly we sought to dissect this interaction. Using C-terminal deletion constructs of the HIP1 helical domain, we identified a region between residues 450 and 456 that is required for CLC binding. Within this region, point mutations showed the importance of residues Leu-451, Leu-452, and Arg-453. Mutants that fail to bind CLC are unable to promote clathrin assembly in vitro but still mediate HIP1 homodimerization and heterodimerization with the family member HIP12/HIP1R. Moreover, HIP1 binding to CLC is necessary for HIP1 targeting to clathrin-coated pits and clathrin-coated vesicles. Interestingly, HIP1 binds to a highly conserved region of CLC previously demonstrated to regulate clathrin assembly. These results suggest a role for HIP1/CLC interactions in the regulation of clathrin assembly.

Historical review: another 50th anniversary--new periodicities in coiled coils.

PubMed

Gruber, Markus; Lupas, Andrei N

2003-12-01

In 1953, Francis Crick and Linus Pauling both proposed models of supercoiled alpha helices ('coiled coils') for the structure of keratin. These were the first attempts at modelling the tertiary structure of a protein. Crick emphasized the packing mode of the side-chains ('knobs-into-holes'), which required a periodicity of seven residues over two helical turns (7/2) and a supercoil in the opposite sense of the constituent helices. By contrast, Pauling envisaged a broader set of periodicities (4/1, 7/2, 18/5, 15/4, 11/3) and supercoils of both senses. Crick's model became canonical and the 'heptad repeat' essentially synonymous with coiled coils, but 50 years later new crystal structures and protein sequences show that the less common periodicities envisaged by Pauling also occur in coiled coils, adding a variant packing mode ('knobs-to-knobs') to the standard model. Pauling's laboratory notebooks suggest that he searched unsuccessfully for this packing mode in 1953.

S46 Peptidases are the First Exopeptidases to be Members of Clan PA

PubMed Central

Sakamoto, Yasumitsu; Suzuki, Yoshiyuki; Iizuka, Ippei; Tateoka, Chika; Roppongi, Saori; Fujimoto, Mayu; Inaka, Koji; Tanaka, Hiroaki; Masaki, Mika; Ohta, Kazunori; Okada, Hirofumi; Nonaka, Takamasa; Morikawa, Yasushi; Nakamura, Kazuo T.; Ogasawara, Wataru; Tanaka, Nobutada

2014-01-01

The dipeptidyl aminopeptidase BII (DAP BII) belongs to a serine peptidase family, S46. The amino acid sequence of the catalytic unit of DAP BII exhibits significant similarity to those of clan PA endopeptidases, such as chymotrypsin. However, the molecular mechanism of the exopeptidase activity of family S46 peptidase is unknown. Here, we report crystal structures of DAP BII. DAP BII contains a peptidase domain including a typical double β-barrel fold and previously unreported α-helical domain. The structures of peptide complexes revealed that the α-helical domain covers the active-site cleft and the side chain of Asn330 in the domain forms hydrogen bonds with the N-terminus of the bound peptide. These observations indicate that the α-helical domain regulates the exopeptidase activity of DAP BII. Because S46 peptidases are not found in mammals, we expect that our study will be useful for the design of specific inhibitors of S46 peptidases from pathogens. PMID:24827749

Chiral expression from molecular to macroscopic level via pH modulation in terbium coordination polymers.

PubMed

Huang, Jian; Ding, Hong-Ming; Xu, Yan; Zeng, Dai; Zhu, Hui; Zang, Dong-Mian; Bao, Song-Song; Ma, Yu-Qiang; Zheng, Li-Min

2017-12-14

Chiral expression from the molecular to macroscopic level is common in biological systems, but is difficult to realise for coordination polymers (CPs). The assembly of homochiral CPs in both crystalline and helical forms can provide a bridge for understanding the relationship between the molecular and macroscopic scales of chirality. Herein, we report homochiral helices of [Tb(R- or S-pempH) 3 ]∙2H 2 O (R - or S -1) (pempH 2  = (1-phenylethylamino)methylphosphonic acid) and their crystalline counterparts (R - or S -3), which are formed at different pH of the reaction mixtures under hydrothermal conditions. By combining the experiments and molecular simulations, we propose that the formation of helices of R -1 or S -1 occurs via a hierarchical self-assembly route, which involves twisted packing due to the geometric incompatibility of the different types of chains. The observed chiral transcription from molecules to morphologies is significant for understanding bio-related self-assembly processes on the nano- to macro-scale.

Optically pure, water-stable metallo-helical ‘flexicate’ assemblies with antibiotic activity

NASA Astrophysics Data System (ADS)

Howson, Suzanne E.; Bolhuis, Albert; Brabec, Viktor; Clarkson, Guy J.; Malina, Jaroslav; Rodger, Alison; Scott, Peter

2012-01-01

The helicates—chiral assemblies of two or more metal atoms linked by short or relatively rigid multidentate organic ligands—may be regarded as non-peptide mimetics of α-helices because they are of comparable size and have shown some relevant biological activity. Unfortunately, these beautiful helical compounds have remained difficult to use in the medicinal arena because they contain mixtures of isomers, cannot be optimized for specific purposes, are insoluble, or are too difficult to synthesize. Instead, we have now prepared thermodynamically stable single enantiomers of monometallic units connected by organic linkers. Our highly adaptable self-assembly approach enables the rapid preparation of ranges of water-stable, helicate-like compounds with high stereochemical purity. One such iron(II) ‘flexicate’ system exhibits specific interactions with DNA, promising antimicrobial activity against a Gram-positive bacterium (methicillin-resistant Staphylococcus aureus, MRSA252), but also, unusually, a Gram-negative bacterium (Escherichia coli, MC4100), as well as low toxicity towards a non-mammalian model organism (Caenorhabditis elegans).

Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome

PubMed Central

Shi, Yuan; Chen, Xiang; Elsasser, Suzanne; Stocks, Bradley B.; Tian, Geng; Lee, Byung-Hoon; Shi, Yanhong; Zhang, Naixia; de Poot, Stefanie A. H.; Tuebing, Fabian; Sun, Shuangwu; Vannoy, Jacob; Tarasov, Sergey G.; Engen, John R.; Finley, Daniel; Walters, Kylie J.

2016-01-01

Structured Abstract INTRODUCTION The ubiquitin-proteasome system comprises hundreds of distinct pathways of degradation, which converge at the step of ubiquitin recognition by the proteasome. Five proteasomal ubiquitin receptors have been identified, two that are intrinsic to the proteasome (Rpn10 and Rpn13) and three reversibly associated proteasomal ubiquitin receptors (Rad23, Dsk2, and Ddi1). RATIONALE We found that the five known proteasomal ubiquitin receptors of yeast are collectively nonessential for ubiquitin recognition by the proteasome. We therefore screened for additional ubiquitin receptors in the proteasome and identified subunit Rpn1 as a candidate. We used nuclear magnetic resonance (NMR) spectroscopy to characterize the structure of the binding site within Rpn1, which we term the T1 site. Mutational analysis of this site showed its functional importance within the context of intact proteasomes. T1 binds both ubiquitin and ubiquitin-like (UBL) proteins, in particular the substrate-delivering shuttle factor Rad23. A second site within the Rpn1 toroid, T2, recognizes the UBL domain of deubiquitinating enzyme Ubp6, as determined by hydrogen-deuterium exchange mass spectrometry analysis and validated by amino acid substitution and functional assays. The Rpn1 toroid thus serves a critical scaffolding role within the proteasome, helping to assemble multiple proteasome cofactors as well as substrates. RESULTS Our results indicate that proteasome subunit Rpn1 can recognize both ubiquitin and UBL domains of substrate shuttling factors that themselves bind ubiquitin and function as reversibly-associated proteasomal ubiquitin receptors. Recognition is mediated by the T1 site within the Rpn1 toroid, which supports proteasome function in vivo. We found that the capacity of T1 to recognize both ubiquitin and UBL proteins was shared with Rpn10 and Rpn13. The surprising multiplicity of ubiquitin-recognition domains within the proteasome may promote enhanced, multipoint binding of ubiquitin chains. The structures of the T1 site in its free state and complexed with monoubiquitin or K48-linked diubiquitin were solved, revealing that three neighboring outer helices from the T1 toroid engage two ubiquitins. This binding mode leads to a preference for certain ubiquitin chain types, especially K6- and K48-linked chains, in a distinct configuration that can position substrates close to the entry port of the proteasome. The fate of proteasome-docked ubiquitin conjugates is determined by a competition between deubiquitination and substrate degradation. We find that proximal to the T1 site within the Rpn1 toroid is a second UBL-binding site, T2, that does not assist in ubiquitin chain recognition, but rather in chain disassembly, by binding to the UBL domain of deubiquitinating enzyme Ubp6. Importantly, the UBL interactors at T1 and T2 are distinct, assigning substrate localization to T1 and substrate deubiquitination to T2. CONCLUSION A ligand-binding hotspot was identified in the Rpn1 toroid, consisting of two adjacent receptor sites, T1 and T2. The Rpn1 toroid represents a novel class of binding domains for ubiquitin and UBL proteins. This study thus defines a novel two-site recognition domain intrinsic to the proteasome that uses homologous ubiquitin/UBL-class ligands to assemble substrates, substrate shuttling factors, and a deubiquitinating enzyme in close proximity. A ligand-binding hotspot in the proteasome for assembling substrates and cofactors Schematic (top) and model structure (bottom, left) mapping the UBL-binding Rpn1 T1 (indigo) and T2 (orange) sites. (Bottom, right) Enlarged region of the proteasome to illustrate the Rpn1 T1 and T2 sites bound to a ubiquitin chain (yellow) and deubiquitinating enzyme Ubp6 (green), respectively. PDB 4CR2 and 2B9R were used for this figure. Hundreds of pathways for degradation converge at ubiquitin recognition by proteasome. Here we found that the five known proteasomal ubiquitin receptors are collectively nonessential for ubiquitin recognition, and identified a sixth receptor, Rpn1. A site (T1) in the Rpn1 toroid recognized ubiquitin and ubiquitin-like (UBL) domains of substrate shuttling factors. T1 structures with monoubiquitin or K48 diubiquitin show three neighboring outer helices engaging two ubiquitins. T1 contributes a distinct substrate-binding pathway with preference for K48-linked chains. Proximal to T1 within the Rpn1 toroid is a second UBL-binding site (T2) that assists in ubiquitin chain disassembly, by binding the UBL of deubiquitinating enzyme Ubp6. Thus a two-site recognition domain intrinsic to the proteasome uses homologous ubiquitin/UBL-class ligands to assemble substrates, shuttling factors, and a deubiquitinating enzyme. PMID:26912900

Linking Regions between Helices in Bacteriorhodopsin Revealed

PubMed Central

Agard, David A.; Stroud, Robert M.

1982-01-01

Three-dimensional electron-microscopic structural analysis requires the combination of many different tilted views of the same specimen. The relative difficulty of tilting the sample to high angles >60° without introducing severe distortion due to different focal distances across the specimen entails that the observable range of electron diffraction data is often limited to this range of angles. Thus, it is generally not possible to observe the diffraction maxima that lie within the conical region of reciprocal space around the direction perpendicular to the electron microscope grid. The absence of data in this region leads to a predictable distortion in the object, and for ±60° tilting makes the resolution essentially twice as bad in the direction perpendicular to the grid as it is for the in-plane image. Constrained density map modification and refinement methods can significantly reduce these effects. A method has been developed, tested on model cases, and applied to the electron-microscopic structure determination of bacteriorhodopsin in order to visualize the location of linking regions between helices. Electron-microscopic structural analysis of bacteriorhodopsin (Henderson and Unwin. 1975 Nature [Lond.] 257:28-32.) showed that the molecule consists of seven rods of density each nearly spanning the lipid bilayer. Owing to the distortion introduced by the missing conical region of reciprocal space data, no density was visible for the polypeptide segments linking the α-helices. Density in the refined maps indicates the location of at least five of the extrahelical segments of the polypeptide. The total number of possible ways of interconnecting the helices is reduced from 7! (5,040) to the five most consistent possibilities without recourse to other considerations. In addition, the density for the helical regions is more uniform and cylindrical throughout their length, and the length of the helices increases from 35 to 45 Å, close to the membrane thickness of 49 Å obtained for membranes dried in vacuo. Only three of the five structures consistent with the location of observed linkers place the seventh helix, onto which the chromophore can be attached by reduction in the light, at a position consistent with the main peak for deuterated retinal in the structure, as derived from neutron diffraction analysis. Two of these models are also consistent with the possible location of some of the reduced chromophore on helix B, at lys 40/41 after reduction in the dark, as well as lys 216 on helix G. ImagesFIGURE 8 PMID:7074187

Crystal structure, phase transition and structural deformations in iron borate (Y0.95Bi0.05)Fe3(BO3)4 in the temperature range 90-500 K.

PubMed

Smirnova, Ekaterina S; Alekseeva, Olga A; Dudka, Alexander P; Artemov, Vladimir V; Zubavichus, Yan V; Gudim, Irina A; Bezmaterhykh, Leonard N; Frolov, Kirill V; Lyubutin, Igor S

2018-04-01

An accurate X-ray diffraction study of (Y 0.95 Bi 0.05 )Fe 3 (BO 3 ) 4 single crystals in the temperature range 90-500 K was performed on a laboratory diffractometer and used synchrotron radiation. It was established that the crystal undergoes a diffuse structural phase transition in the temperature range 350-380 K. The complexity of localization of such a transition over temperature was overcome by means of special analysis of systematic extinction reflections by symmetry. The transition temperature can be considered to be T str ≃ 370 K. The crystal has a trigonal structure in the space group P3 1 21 at temperatures of 90-370 K, and it has a trigonal structure in the space group R32 at 375-500 K. There is one type of chain formed by the FeO 6 octahedra along the c axis in the R32 phase. When going into the P3 1 21 phase, two types of nonequivalent chains arise, in which Fe atoms are separated from the Y atoms by a different distance. Upon lowering the temperature from 500 to 90 K, a distortion of the Y(Bi)O 6 , FeO 6 , B(2,3)O 3 coordination polyhedra is observed. The distances between atoms in helical Fe chains and Fe-O-Fe angles change non-uniformly. A sharp jump in the equivalent isotropic displacement parameters of O1 and O2 atoms within the Fe-Fe chains and fluctuations of the equivalent isotropic displacement parameters of B2 and B3 atoms were observed in the region of structural transition as well as noticeable elongation of O1, O2, B2, B3, Fe1, Fe2 atomic displacement ellipsoids. It was established that the helices of electron density formed by Fe, O1 and O2 atoms may be structural elements determining chirality, optical activity and multiferroicity of rare-earth iron borates. Compression and stretching of these helices account for the symmetry change and for the manifestation of a number of properties, whose geometry is controlled by an indirect exchange interaction between iron cations that compete with the thermal motion of atoms in the structure. Structural analysis detected these changes as variations of a number of structural characteristics in the c unit-cell direction, that is, the direction of the helices. Structural results for the local surrounding of the atoms in (Y 0.95 Bi 0.05 )Fe 3 (BO 3 ) 4 were confirmed by EXAFS and Mössbauer spectroscopies.

Spontaneous translocation of antitumor oxaliplatin, its enantiomeric analogue, and Cisplatin from one strand to another in double-helical DNA.

PubMed

Malina, Jaroslav; Natile, Giovanni; Brabec, Viktor

2013-09-02

Oxaliplatin and cisplatin belong to the class of platinum-based anticancer agents. Formation of DNA adducts by these complexes and the consequences for its structure and function, is the mechanistic paradigm by which these drugs exert their antitumor activity. We show that employing short oligonucleotide duplexes containing single, site-specific 1,3-intrastrand cross-links of oxaliplatin, its enantiomeric analogue, or cisplatin and by using gel electrophoresis that under physiological conditions the coordination bonds between platinum and the N7 position of guanine residues involved in the cross-links of the Pt(II) complexes can be cleaved. This cleavage may lead to linkage isomerization reactions between these metallodrugs and double-helical DNA. For instance, approximately 25 % 1,3-intrastrand cross-links of the platinum complexes isomerized after 192 h (at 310 K in 200 mM NaClO4). Differential scanning calorimetry of duplexes containing single, site-specific cross-links of oxaliplatin, its enantiomeric analogue, and cisplatin reveals that one of the driving forces that leads to the lability of DNA cross-links of these metallodrugs is a difference between the thermodynamic destabilization induced by the cross-link and by the adduct into which it could isomerize. The rearrangements may proceed in the way that cross-links originally formed in one strand of the DNA can spontaneously translocate from one DNA strand to its complementary counterpart, which may evoke walking of the platinum complex on DNA molecule. In addition, the differences in the kinetics of the rearrangement reactions and the thermodynamic destabilization of DNA observed for adducts of oxaliplatin and its enantiomeric analogue confirm that the chirality at the carrier 1,2-diaminocyclohexane ligand can considerably affect structural and other physical properties of DNA adducts and consequently their biological effects. In aggregate, interesting generalization of the results described in this work might be that the migration of oxaliplatin, its enantiomeric analogue, or cisplatin from one strand to another in double-helical DNA controlled by energetic signatures of these agents might contribute to a better understanding of their cytotoxic and mutagenic potential. Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of Magnetic Flux Rope Chains Embedded in Martian Current Sheets Using MAVEN Data

NASA Astrophysics Data System (ADS)

Bowers, C. F.; DiBraccio, G. A.; Brain, D.; Hara, T.; Gruesbeck, J.; Espley, J. R.; Connerney, J. E. P.; Halekas, J. S.

2017-12-01

The magnetotail of Mars is formed as the interplanetary magnetic field (IMF) drapes around the planet's conducting ionosphere and localized crustal magnetic fields. In this scenario, a cross-tail current sheet separates the sunward and anti-sunward tail lobes. This tail current sheet is a highly dynamic region where magnetic reconnection is able to occur between the oppositely oriented fields. Magnetic flux ropes, a by-product of magnetic reconnection in the tail or in the ionosphere characterized by their helical outer wraps and strong axial core field, are commonly observed in the Martian magnetotail. An initial study using Mars Global Surveyor measurements reported a chain of flux ropes in the tail. During this event, 3 flux ropes were observed during a single traversal of the tail current sheet with a duration of 4 minutes. Here, we perform a statistical survey of these chain-of-flux-rope events to characterize their occurrence in the tail current sheet using Mars Atmosphere and Volatile EvolutioN (MAVEN) data. We implement the well-established technique of Minimum Variance Analysis to confirm the helical structure of the flux ropes and also determine local current sheet orientation. Thorough visual examination of more than 1600 orbits has resulted in the identification of 784 tail current sheet traversals. We determine the current sheet thickness to be on the order of 100-1000 km. From these current sheet observations, a subset of 30 events include embedded chain of flux ropes within the current sheet structure. We find that 87% of these flux rope chain events are identified in the southern latitude regions of Mars, associated with crustal fields. Their location suggests that magnetic reconnection occurring near crustal fields may be the source of these flux ropes. These statistical measurements of both current sheets and associated flux rope chains provide information about the complex magnetospheric dynamics at Mars, and how these dynamics affect atmospheric loss to space.

Analysis of Nuclear Factor-κB (NF-κB) Essential Modulator (NEMO) Binding to Linear and Lysine-linked Ubiquitin Chains and Its Role in the Activation of NF-κB*

PubMed Central

Kensche, Tobias; Tokunaga, Fuminori; Ikeda, Fumiyo; Goto, Eiji; Iwai, Kazuhiro; Dikic, Ivan

2012-01-01

Nuclear factor-κB (NF-κB) essential modulator (NEMO), a component of the inhibitor of κB kinase (IKK) complex, controls NF-κB signaling by binding to ubiquitin chains. Structural studies of NEMO provided a rationale for the specific binding between the UBAN (ubiquitin binding in ABIN and NEMO) domain of NEMO and linear (Met-1-linked) di-ubiquitin chains. Full-length NEMO can also interact with Lys-11-, Lys-48-, and Lys-63-linked ubiquitin chains of varying length in cells. Here, we show that purified full-length NEMO binds preferentially to linear ubiquitin chains in competition with lysine-linked ubiquitin chains of defined length, including long Lys-63-linked deca-ubiquitins. Linear di-ubiquitins were sufficient to activate both the IKK complex in vitro and to trigger maximal NF-κB activation in cells. In TNFα-stimulated cells, NEMO chimeras engineered to bind exclusively to Lys-63-linked ubiquitin chains mediated partial NF-κB activation compared with cells expressing NEMO that binds to linear ubiquitin chains. We propose that NEMO functions as a high affinity receptor for linear ubiquitin chains and a low affinity receptor for long lysine-linked ubiquitin chains. This phenomenon could explain quantitatively distinct NF-κB activation patterns in response to numerous cell stimuli. PMID:22605335

Favorable Influence of Hydrophobic Surfaces on Protein Structure in Porous Organically-modified Silica Glasses

PubMed Central

Menaa, Bouzid; Herrero, Mar; Rives, Vicente; Lavrenko, Mayya; Eggers, Daryl K.

2008-01-01

Organically-modified siloxanes were used as host materials to examine the influence of surface chemistry on protein conformation in a crowded environment. The sol-gel materials were prepared from tetramethoxysilane and a series of monosubstituted alkoxysilanes, RSi(OR′)3, featuring alkyl groups of increasing chain length in the R-position. Using circular dichroism spectroscopy in the far-UV region, apomyoglobin was found to transit from an unfolded state to a native-like helical state as the content of the hydrophobic precursor increased from 0–15%. At a fixed molar content of 5% RSi(OR’)3, the helical structure of apomyoglobin increased with the chain length of the R-group, i.e. methyl < ethyl < n-propyl < n-butyl < n-hexyl. This trend also was observed for the tertiary structure of ribonuclease A, suggesting that protein folding and biological activity are sensitive to the hydrophilic/hydrophobic balance of neighboring surfaces. The observed changes in protein structure did not correlate with total surface area or the average pore size of the modified glasses, but scanning electron microscopy images revealed an interesting relationship between surface morphology and alkyl chain length. The unexpected benefit of incorporating a low content of hydrophobic groups into a hydrophilic surface may lead to materials with improved biocompatibility for use in biosensors and implanted devices. PMID:18359512

The Role of Magnetic Helicity in Structuring the Solar Corona

NASA Technical Reports Server (NTRS)

Knizhnik, K. J.; Antiochos, S. K.; DeVore, C. R.

2017-01-01

Two of the most widely observed and striking features of the Suns magnetic field are coronal loops, which are smooth and laminar, and prominences or filaments, which are strongly sheared. Loops are puzzling because they show little evidence of tangling or braiding, at least on the quiet Sun, despite the chaotic nature of the solar surface convection. Prominences are mysterious because the origin of their underlying magnetic structure filament channels is poorly understood at best. These two types of features would seem to be quite unrelated and wholly distinct. We argue that, on the contrary, they are inextricably linked and result from a single process: the injection of magnetic helicity into the corona by photospheric motions and the subsequent evolution of this helicity by coronal reconnection. In this paper, we present numerical simulations of the response of a Parker (1972) corona to photospheric driving motions that have varying degrees of helicity preference. We obtain four main conclusions: (1) in agreement with the helicity condensation model of Antiochos (2013), the inverse cascade of helicity by magnetic reconnection in the corona results in the formation of filament channels localized about polarity inversion lines; (2) this same process removes most complex fine structure from the rest of the corona, resulting in smooth and laminar coronal loops; (3) the amount of remnant tangling in coronal loops is inversely dependent on the net helicity injected by the driving motions; and (4) the structure of the solar corona depends only on the helicity preference of the driving motions and not on their detailed time dependence. We discuss the implications of our results for high-resolution observations of the corona.

THE ROLE OF MAGNETIC HELICITY IN STRUCTURING THE SOLAR CORONA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knizhnik, K. J.; Antiochos, S. K.; DeVore, C. R.

Two of the most widely observed and striking features of the Sun's magnetic field are coronal loops, which are smooth and laminar, and prominences or filaments, which are strongly sheared. Loops are puzzling because they show little evidence of tangling or braiding, at least on the quiet Sun, despite the chaotic nature of the solar surface convection. Prominences are mysterious because the origin of their underlying magnetic structure—filament channels—is poorly understood at best. These two types of features would seem to be quite unrelated and wholly distinct. We argue that, on the contrary, they are inextricably linked and result frommore » a single process: the injection of magnetic helicity into the corona by photospheric motions and the subsequent evolution of this helicity by coronal reconnection. In this paper, we present numerical simulations of the response of a Parker (1972) corona to photospheric driving motions that have varying degrees of helicity preference. We obtain four main conclusions: (1) in agreement with the helicity condensation model of Antiochos (2013), the inverse cascade of helicity by magnetic reconnection in the corona results in the formation of filament channels localized about polarity inversion lines; (2) this same process removes most complex fine structure from the rest of the corona, resulting in smooth and laminar coronal loops; (3) the amount of remnant tangling in coronal loops is inversely dependent on the net helicity injected by the driving motions; and (4) the structure of the solar corona depends only on the helicity preference of the driving motions and not on their detailed time dependence. We discuss the implications of our results for high-resolution observations of the corona.« less

Conversion of Natively Unstructured α-Synuclein to Its α-Helical Conformation Significantly Attenuates Production of Reactive Oxygen Species

PubMed Central

Zhou, Binbin; Hao, Yuanqiang; Wang, Chengshan; Li, Ding; Liu, You-Nian; Zhou, Feimeng

2012-01-01

The intracellular α-synuclein (α-syn) protein, whose conformational change and aggregation have been closely linked to the pathology of Parkingson’s disease (PD), is highly populated at the presynaptic termini and remains there in the α-helical conformation. In this study, circular dichroism confirmed that natively unstructured α-syn in aqueous solution was transformed to its α-helical conformation upon addition of trifluoroethanol (TFE). Electrochemical and UV–visible spectroscopic experiments reveal that both Cu(I) and Cu(II) are stabilized, with the former being stabilized by about two orders of magnitude. Compared to unstructured α-syn (Binolfi et al., J. Am. Chem. Soc. 133 (2011) 194–196), α-helical α-syn stabilizes Cu(I) by more than three orders of magnitude. Through the measurements of H2O2 and hydroxyl radicals (OH•) in solutions containing different forms of Cu(II) (free and complexed by unstructured or α-helical α-syn), we demonstrate that the significantly enhanced Cu(I) binding affinity helps inhibit the production of highly toxic reactive oxygen species, especially the hydroxyl radicals. Our study provides strong evidence that, as a possible means to prevent neuronal cell damage, conversion of the natively unstructured α-syn to its α-helical conformation in vivo could significantly attenuate the copper-modulated ROS production. PMID:23123341

Effect of Chain Conformation on the Single-Molecule Melting Force in Polymer Single Crystals: Steered Molecular Dynamics Simulations Study.

PubMed

Feng, Wei; Wang, Zhigang; Zhang, Wenke

2017-02-28

Understanding the relationship between polymer chain conformation as well as the chain composition within the single crystal and the mechanical properties of the corresponding single polymer chain will facilitate the rational design of high performance polymer materials. Here three model systems of polymer single crystals, namely poly(ethylene oxide) (PEO), polyethylene (PE), and nylon-66 (PA66) have been chosen to study the effects of chain conformation, helical (PEO) versus planar zigzag conformation (PE, PA66), and chain composition (PE versus PA66) on the mechanical properties of a single polymer chain. To do that, steered molecular dynamics simulations were performed on those polymer single crystals by pulling individual polymer chains out of the crystals. Our results show that the patterns of force-extension curve as well as the chain moving mode are closely related to the conformation of the polymer chain in the single crystal. In addition, hydrogen bonds can enhance greatly the force required to stretch the polymer chain out of the single crystal. The dynamic breaking and reformation of multivalent hydrogen bonds have been observed for the first time in PA66 at the single molecule level.

Stereochemical model for proflavin intercalation in A-DNA.

PubMed Central

Alden, C J; Arnott, S

1977-01-01

Linked-atom molecular modelling was employed to determine the steric and torsional requirements for intercalation of proflavine into a double-stranded region of DNA compatible with adjacent regions of cohelical A-DNA. The optimum intercalation conformation is characterized by the dihedral angles xi and psi becoming trans, with all sugars retaining the characteristics C3'-endo pucker. This extended conformation results in virtually no helical unwinding, suggesting it may be an appropriate model for an intercalative intermediary in mutagenesis by virtue of its similarity to standard helical DNA. PMID:593890

The hydration of amides in helices; a comprehensive picture from molecular dynamics, IR, and NMR

PubMed Central

Walsh, Scott T.R.; Cheng, Richard P.; Wright, Wayne W.; Alonso, Darwin O.V.; Daggett, Valerie; Vanderkooi, Jane M.; DeGrado, William F.

2003-01-01

We examined the hydration of amides of α3D, a simple, designed three-helix bundle protein. Molecular dynamics calculations show that the amide carbonyls on the surface of the protein tilt away from the helical axis to interact with solvent water, resulting in a lengthening of the hydrogen bonds on this face of the helix. Water molecules are bonded to these carbonyl groups with partial occupancy (∼50%–70%), and their interaction geometries show a large variation in their hydrogen bond lengths and angles on the nsec time scale. This heterogeneity is reflected in the carbonyl stretching vibration (amide I′ band) of a group of surface Ala residues. The surface-exposed amides are broad, and shift to lower frequency (reflecting strengthening of the hydrogen bonds) as the temperature is decreased. By contrast, the amide I′ bands of the buried 13C-labeled Leu residues are significantly sharper and their frequencies are consistent with the formation of strong hydrogen bonds, independent of temperature. The rates of hydrogen-deuterium exchange and the proton NMR chemical shifts of the helical amide groups also depend on environment. The partial occupancy of the hydration sites on the surface of helices suggests that the interaction is relatively weak, on the order of thermal energy at room temperature. One unexpected feature that emerged from the dynamics calculations was that a Thr side chain subtly disrupted the helical geometry 4–7 residues N-terminal in sequence, which was reflected in the proton chemical shifts and the rates of amide proton exchange for several amides that engage in a mixed 310/α/π-helical conformation. PMID:12592022

The structure of the ends of α-helices in globular proteins: effect of additional hydrogen bonds and implications for helix formation.

PubMed

Leader, David P; Milner-White, E James

2011-03-01

We prepared a set of about 2000 α-helices from a relational database of high-resolution three-dimensional structures of globular proteins, and identified additional main chain i ← i+3 hydrogen bonds at the ends of the helices (i.e., where the hydrogen bonding potential is not fulfilled by canonical i ← i+4 hydrogen bonds). About one-third of α-helices have such additional hydrogen bonds at the N-terminus, and more than half do so at the C-terminus. Although many of these additional hydrogen bonds at the C-terminus are associated with Schellman loops, the majority are not. We compared the dihedral angles at the termini of α-helices having or lacking the additional hydrogen bonds. Significant differences were found, especially at the C-terminus, where the dihedral angles at positions C2 and C1 in the absence of additional hydrogen bonds deviate substantially from those occurring within the α-helix. Using a novel approach we show how the structure of the C-terminus of the α-helix can emerge from that of constituent overlapping α-turns and β-turns, which individually show a variation in dihedral angles at different positions. We have also considered the direction of propagation of the α-helix using this approach. If one assumes that helices start as a single α-turn and grow by successive addition of further α-turns, the paths for growth in the N → C and C → N directions differ in a way that suggests that extension in the C → N direction is favored. Copyright © 2010 Wiley-Liss, Inc.

Structural and biophysical characterization of an epitope-specific engineered Fab fragment and complexation with membrane proteins: implications for co-crystallization.

PubMed

Johnson, Jennifer L; Entzminger, Kevin C; Hyun, Jeongmin; Kalyoncu, Sibel; Heaner, David P; Morales, Ivan A; Sheppard, Aly; Gumbart, James C; Maynard, Jennifer A; Lieberman, Raquel L

2015-04-01

Crystallization chaperones are attracting increasing interest as a route to crystal growth and structure elucidation of difficult targets such as membrane proteins. While strategies to date have typically employed protein-specific chaperones, a peptide-specific chaperone to crystallize multiple cognate peptide epitope-containing client proteins is envisioned. This would eliminate the target-specific chaperone-production step and streamline the co-crystallization process. Previously, protein engineering and directed evolution were used to generate a single-chain variable (scFv) antibody fragment with affinity for the peptide sequence EYMPME (scFv/EE). This report details the conversion of scFv/EE to an anti-EE Fab format (Fab/EE) followed by its biophysical characterization. The addition of constant chains increased the overall stability and had a negligible impact on the antigen affinity. The 2.0 Å resolution crystal structure of Fab/EE reveals contacts with larger surface areas than those of scFv/EE. Surface plasmon resonance, an enzyme-linked immunosorbent assay, and size-exclusion chromatography were used to assess Fab/EE binding to EE-tagged soluble and membrane test proteins: namely, the β-barrel outer membrane protein intimin and α-helical A2a G protein-coupled receptor (A2aR). Molecular-dynamics simulation of the intimin constructs with and without Fab/EE provides insight into the energetic complexities of the co-crystallization approach.

Conformation and hydration of surface grafted and free polyethylene oxide chains in solutions

NASA Astrophysics Data System (ADS)

Dahal, Udaya; Wang, Zilu; Dormidontova, Elena

Due to the wide application of polyethylene oxide (PEO), ranging from biomedicine to fuel cells, it is one of the most studied polymers in the scientific world. In order to elucidate detailed molecular-level insights on the impact of surface grafting on PEO conformation, we performed atomistic molecular dynamics simulations of PEO chains in solution and grafted to a flat gold surface in different solvents. We examined the hydration as well as conformation of the free chain compared to the grafted polymer in pure water and mixed solvents. We find that grafted chains are stiffer and have a stronger tendency to form helical structures in isobutyric acid or mixture of isobutyric acid and water solution than the free chains in corresponding solutions. For grafted chains exposed to pure water the random coil conformation is retained at low grafting density, but becomes stretched and more dehydrated as the grafting density or temperature increases. This research is supported by NSF (DMR-1410928).

SSEP: secondary structural elements of proteins

PubMed Central

Shanthi, V.; Selvarani, P.; Kiran Kumar, Ch.; Mohire, C. S.; Sekar, K.

2003-01-01

SSEP is a comprehensive resource for accessing information related to the secondary structural elements present in the 25 and 90% non-redundant protein chains. The database contains 1771 protein chains from 1670 protein structures and 6182 protein chains from 5425 protein structures in 25 and 90% non-redundant protein chains, respectively. The current version provides information about the α-helical segments and β-strand fragments of varying lengths. In addition, it also contains the information about 310-helix, β- and ν-turns and hairpin loops. The free graphics program RASMOL has been interfaced with the search engine to visualize the three-dimensional structures of the user queried secondary structural fragment. The database is updated regularly and is available through Bioinformatics web server at http://cluster.physics.iisc.ernet.in/ssep/ or http://144.16.71.148/ssep/. PMID:12824336

Disordering Chain Motions in Fluoropolymers

NASA Astrophysics Data System (ADS)

Holt, David B.; Farmer, Barry L.

1998-03-01

Rotational and conformational disorder play important roles in the solid state phases of fluoropolymers such as polytetrafluoro- ethylene (PTFE). Modeling disordering processes and transitions which occur in fluoropolymers has been hampered due to a lack of force field parameters that adequately describe both the intra- and intermolecular characteristics (conformations and distances) of these polymers in the solid state. A force field has been developed which overcomes these inadequacies and has been utilized in molecular dynamics simulations on a system of PTFE oligomers to investigate two of the primary disordering processes that occur in the solid phases: rotations of chains about their helical axes and the formation and subsequent behavior of helix reversals. The simulation results confirm helix reversal activity at low temperatures and demonstrate correlations between chain segment rotations or librations and helix reversal motion. A mechanism for large scale chain segment rotations is proposed.

HTLV-1 Tax Induces Formation of the Active Macromolecular IKK Complex by Generating Lys63- and Met1-Linked Hybrid Polyubiquitin Chains.

PubMed

Shibata, Yuri; Tokunaga, Fuminori; Goto, Eiji; Komatsu, Ginga; Gohda, Jin; Saeki, Yasushi; Tanaka, Keiji; Takahashi, Hirotaka; Sawasaki, Tatsuya; Inoue, Satoshi; Oshiumi, Hiroyuki; Seya, Tsukasa; Nakano, Hiroyasu; Tanaka, Yuetsu; Iwai, Kazuhiro; Inoue, Jun-Ichiro

2017-01-01

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation.

HTLV-1 Tax Induces Formation of the Active Macromolecular IKK Complex by Generating Lys63- and Met1-Linked Hybrid Polyubiquitin Chains

PubMed Central

Tokunaga, Fuminori; Goto, Eiji; Komatsu, Ginga; Saeki, Yasushi; Tanaka, Keiji; Takahashi, Hirotaka; Sawasaki, Tatsuya; Inoue, Satoshi; Oshiumi, Hiroyuki; Seya, Tsukasa; Nakano, Hiroyasu; Tanaka, Yuetsu; Iwai, Kazuhiro

2017-01-01

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation. PMID:28103322

A periodic table of coiled-coil protein structures.

PubMed

Moutevelis, Efrosini; Woolfson, Derek N

2009-01-23

Coiled coils are protein structure domains with two or more alpha-helices packed together via interlacing of side chains known as knob-into-hole packing. We analysed and classified a large set of coiled-coil structures using a combination of automated and manual methods. This led to a systematic classification that we termed a "periodic table of coiled coils," which we have made available at http://coiledcoils.chm.bris.ac.uk/ccplus/search/periodic_table. In this table, coiled-coil assemblies are arranged in columns with increasing numbers of alpha-helices and in rows of increased complexity. The table provides a framework for understanding possibilities in and limits on coiled-coil structures and a basis for future prediction, engineering and design studies.

The parallel reaction monitoring method contributes to a highly sensitive polyubiquitin chain quantification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsuchiya, Hikaru; Tanaka, Keiji, E-mail: tanaka-kj@igakuken.or.jp; Saeki, Yasushi, E-mail: saeki-ys@igakuken.or.jp

2013-06-28

Highlights: •The parallel reaction monitoring method was applied to ubiquitin quantification. •The ubiquitin PRM method is highly sensitive even in biological samples. •Using the method, we revealed that Ufd4 assembles the K29-linked ubiquitin chain. -- Abstract: Ubiquitylation is an essential posttranslational protein modification that is implicated in a diverse array of cellular functions. Although cells contain eight structurally distinct types of polyubiquitin chains, detailed function of several chain types including K29-linked chains has remained largely unclear. Current mass spectrometry (MS)-based quantification methods are highly inefficient for low abundant atypical chains, such as K29- and M1-linked chains, in complex mixtures thatmore » typically contain highly abundant proteins. In this study, we applied parallel reaction monitoring (PRM), a quantitative, high-resolution MS method, to quantify ubiquitin chains. The ubiquitin PRM method allows us to quantify 100 attomole amounts of all possible ubiquitin chains in cell extracts. Furthermore, we quantified ubiquitylation levels of ubiquitin-proline-β-galactosidase (Ub-P-βgal), a historically known model substrate of the ubiquitin fusion degradation (UFD) pathway. In wild-type cells, Ub-P-βgal is modified with ubiquitin chains consisting of 21% K29- and 78% K48-linked chains. In contrast, K29-linked chains are not detected in UFD4 knockout cells, suggesting that Ufd4 assembles the K29-linked ubiquitin chain(s) on Ub-P-βgal in vivo. Thus, the ubiquitin PRM is a novel, useful, quantitative method for analyzing the highly complicated ubiquitin system.« less

cDNA cloning and characterization of Type I procollagen alpha1 chain in the skate Raja kenojei.

PubMed

Hwang, Jae-Ho; Yokoyama, Yoshihiro; Mizuta, Shoshi; Yoshinaka, Reiji

2006-05-01

A full-length cDNA of the Type I procollagen alpha1 [pro-alpha1(I)] chain (4388 bp), coding for 1463 amino acid residues in the total length, was determined by RACE PCR using a cDNA library constructed from 4-week embryo of the skate Raja kenojei. The helical region of the skate pro-alpha1(I) chain consisted of 1014 amino acid residues - the same as other fibrillar collagen alpha chains from higher vertebrates. Comparison on denaturation temperatures of Type I collagens from the skate, rainbow trout (Oncorhynchus mykiss) and rat (Rattus norvegicus) revealed that the number of Gly-Pro-Pro and Gly-Gly in the alpha1(I) chains could be directly related to the thermal stability of the helix. The expression property of the skate pro-alpha1(I) chain mRNA and phylogenetic analysis with other vertebrate pro-alpha1(I) chains suggested that skate pro-alpha1(I) chain could be a precursor form of the skate Type I collagen alpha1 chain. The present study is the first evidence for the primary structure of full-length pro-alpha1(I) chain in an elasmobranch.

Raman spectroscopic study of the conformation of dicarboxylic acid salts in aqueous solutions

NASA Astrophysics Data System (ADS)

Fukushima, Kunio; Watanabe, Toshiaki; Umemura, Matome

1986-08-01

It is already known that the molecules of long chain monocarboxylic acid salts have a tendency to form micelles in aqueous solutions, the molecular chain taking the all- trans zigzag structure. However it is considered difficult for dicarboxylic acid salts to adopt the same structure as the monocarboxylic acid salts as they have two carboxyl groups, one on each end of the molecular chain. Therefore, a special structure is expected to exist for dicarboxylic acid salts in aqueous solution. In order to examine this, Raman spectra of suberic acid salt and azelaic acid salt in aqueous solution were measured and the normal vibrational calculation carried out, showing that dicarboxylic acid salts have a helical structure in aqueous solution.

Nonlinear vibrational excitations in molecular crystals molecular mechanics calculations

NASA Astrophysics Data System (ADS)

Pumilia, P.; Abbate, S.; Baldini, G.; Ferro, D. R.; Tubino, R.

1992-03-01

The coupling constant for vibrational solitons χ has been examined in a molecular mechanics model for acetanilide (ACN) molecular crystal. According to A.C. Scott, solitons can form and propagate in solid acetanilide over a threshold energy value. This can be regarded as a structural model for the spines of hydrogen bond chains stabilizing the α helical structure of proteins. A one dimensional hydrogen bond chain of ACN has been built, for which we have found that, even though experimental parameters are correctly predicted, the excessive rigidity of the isolated chain prevents the formation of a localized distortion around the excitation. Yet, C=O coupling value with softer lattice modes could be rather high, allowing self-trapping to take place.

Ufd2p synthesizes branched ubiquitin chains to promote the degradation of substrates modified with atypical chains

PubMed Central

Liu, Chao; Liu, Weixiao; Ye, Yihong; Li, Wei

2017-01-01

Ubiquitination of a subset of proteins by ubiquitin chain elongation factors (E4), represented by Ufd2p in Saccharomyces cerevisiae, is a pivotal regulator for many biological processes. However, the mechanism of Ufd2p-mediated ubiquitination is largely unclear. Here, we show that Ufd2p catalyses K48-linked multi-monoubiquitination on K29-linked ubiquitin chains assembled by the ubiquitin ligase (Ufd4p), resulting in branched ubiquitin chains. This reaction depends on the interaction of K29-linked ubiquitin chains with two N-terminal loops of Ufd2p. Only following the addition of K48-linked ubiquitin to substrates modified with K29-linked ubiquitin chains, can the substrates be escorted to the proteasome for degradation. We demonstrate that this ubiquitin chain linkage switching reaction is essential for ERAD, oleic acid and acid pH resistance in yeast. Thus, our results suggest that Ufd2p functions by switching ubiquitin chain linkages to allow the degradation of proteins modified with a ubiquitin linkage, which is normally not targeted to the proteasome. PMID:28165462

Effects of hydrophobic helix length and side chain chemistry on biomimicry in peptoid analogues of SP-C.

PubMed

Brown, Nathan J; Wu, Cindy W; Seurynck-Servoss, Shannon L; Barron, Annelise E

2008-02-12

The hydrophobic proteins of lung surfactant (LS), SP-B and SP-C, are critical constituents of an effective surfactant replacement therapy for the treatment of respiratory distress syndrome. Because of concerns and difficulties associated with animal-derived surfactants, recent investigations have focused on the creation of synthetic analogues of the LS proteins. However, creating an accurate mimic of SP-C that retains its biophysical surface activity is extraordinarily challenging given the lipopeptide's extreme hydrophobicity and propensity to misfold and aggregate. One successful approach that overcomes these difficulties is the use of poly-N-substituted glycines, or peptoids, to mimic SP-C. To develop a non-natural, bioactive mimic of SP-C and to investigate the effects of side chain chemistry and length of the helical hydrophobic region, we synthesized, purified, and performed in vitro testing of two classes of peptoid SP-C mimics: those having a rigid alpha-chiral aromatic helix and those having a biomimetic alpha-chiral aliphatic helix. The length of the two classes of mimics was also systematically altered. Circular dichroism spectroscopy gave evidence that all of the peptoid-based mimics studied here emulated SP-C's secondary structure, forming stable helical structures in solution. Langmuir-Wilhelmy surface balance, fluorescence microscopy, and pulsating bubble surfactometry experiments provide evidence that the aromatic-based SP-C peptoid mimics, in conjunction with a synthetic lipid mixture, have superior surface activity and biomimetic film morphology in comparison to the aliphatic-based mimics and that there is an increase in surface activity corresponding to increasing helical length.

Conformational statistics of stiff macromolecules as solutions to partial differential equations on the rotation and motion groups

PubMed

Chirikjian; Wang

2000-07-01

Partial differential equations (PDE's) for the probability density function (PDF) of the position and orientation of the distal end of a stiff macromolecule relative to its proximal end are derived and solved. The Kratky-Porod wormlike chain, the Yamakawa helical wormlike chain, and the original and revised Marko-Siggia models are examples of stiffness models to which the present formulation is applied. The solution technique uses harmonic analysis on the rotation and motion groups to convert PDE's governing the PDF's of interest into linear algebraic equations which have mathematically elegant solutions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chao, Tzu-Ling; Yang, Chen-I., E-mail: ciyang@thu.edu.tw

The preparations and properties of three new homochiral three-dimensional (3D) coordination polymers, [M(D-cam)(pyz)(H{sub 2}O){sub 2}]{sub n} (M=Co (1) and Ni (2); D-H{sub 2}cam=(+) D-camphoric acid; pyz=pyrazine) and [Mn{sub 2}(D-cam){sub 2}(H{sub 2}O){sub 2}] (3), under solvothermal conditions is described. Single-crystal X-ray diffraction analyses revealed that all of compounds are homochiral 3D structure. 1 and 2 are isostructural and crystallize in the trigonal space group P3{sub 2}21, while 3 crystallizes in monoclinic space group P2{sub 1}. The structure of 1 and 2 consists of metal-D-cam helical chains which are pillared with pyrazine ligands into a 3D framework structure and 3 features amore » 3D homochiral framework involving one-dimensional manganese-carboxylate chains that are aligned parallel to the b axis. Magnetic susceptibility data of all compounds were collected. The findings indicate that μ{sub 2}-pyrazine dominate weak antiferromagnetic coupling within 1 and 2, while 3 exhibits antiferromagnetic behavior through the carboxylate groups of D-cam ligand. -- Graphical abstract: The preparations and properties of three new homochiral three-dimensional (3D) coordination polymers, [M(D-cam)(pyz)(H{sub 2}O){sub 2}]{sub n} (M=Co (1) and Ni (2); D-H{sub 2}cam=(+) D-camphoric acid; pyz=pyrazine) and [Mn{sub 2}(D-cam){sub 2}(H{sub 2}O){sub 2}] (3), under solvothermal conditions is described. Single-crystal X-ray diffraction analyses revealed that all of compounds are homochiral 3D structure. 1 and 2 are isostructural and crystallize in the trigonal space group P3{sub 2}21, while 3 crystallizes in monoclinic space group P2{sub 1}. The structure of 1 and 2 consists of metal-D-cam helical chains which are pillared with pyrazine ligands into a 3D framework structure and 3 features a 3D homochiral framework involving one-dimensional manganese-carboxylate chains that are aligned parallel to the b axis. Magnetic susceptibility data of all compounds were collected. The findings indicate that μ{sub 2}-pyrazine dominate weak antiferromagnetic coupling within 1 and 2, while 3 exhibits antiferromagnetic behavior through the carboxylate groups of D-cam ligand. Highlights: • Three homochiral 3D coordination polymers were synthesized. • 1 and 2 are 3D structure with metal-D-cam helical chains pillared by pyrazine. • 3 shows a 3D homochiral framework involving 1D manganese-carboxylate chains. • Magnetic data analysis indicates that 1–3 exhibit weak antiferromagnetic coupling.« less

Walking of antitumor bifunctional trinuclear PtII complex on double-helical DNA

PubMed Central

Malina, Jaroslav; Kasparkova, Jana; Farrell, Nicholas P.; Brabec, Viktor

2011-01-01

The trinuclear BBR3464 ([{trans-PtCl(NH3)2}2µ-(trans-Pt(NH3)2(H2N(CH2)6NH2)2)]4+) belongs to the polynuclear class of platinum-based anticancer agents. DNA adducts of this complex differ significantly in structure and type from those of clinically used mononuclear platinum complexes, especially, long-range (Pt, Pt) intrastrand and interstrand cross-links are formed in both 5′–5′ and 3′–3′ orientations. We show employing short oligonucleotide duplexes containing single, site-specific cross-links of BBR3464 and gel electrophoresis that in contrast to major DNA adducts of clinically used platinum complexes, under physiological conditions the coordination bonds between platinum and N7 of G residues involved in the cross-links of BBR3464 can be cleaved. This cleavage may lead to the linkage isomerization reactions between this metallodrug and double-helical DNA. Differential scanning calorimetry of duplexes containing single, site-specific cross-links of BBR3464 reveals that one of the driving forces that leads to the lability of DNA cross-links of this metallodrug is a difference between the thermodynamic destabilization induced by the cross-link and by the adduct into which it could isomerize. The rearrangements may proceed in the way that cross-links originally formed in one strand of DNA can spontaneously translocate from one DNA strand to its complementary counterpart, which may evoke walking of the platinum complex on DNA molecule. PMID:20833634

Recombinant expression and solution structure of antimicrobial peptide aurelin from jellyfish Aurelia aurita

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shenkarev, Zakhar O.; Panteleev, Pavel V.; Balandin, Sergey V.

Highlights: Black-Right-Pointing-Pointer Aurelin was overexpressed in Escherichia coli, and its spatial structure was studied by NMR. Black-Right-Pointing-Pointer Aurelin compact structure encloses helical regions cross-linked by three disulfide bonds. Black-Right-Pointing-Pointer Aurelin shows structural homology to the BgK and ShK toxins of sea anemones. Black-Right-Pointing-Pointer Aurelin binds to the anionic lipid vesicles, but does not interact with zwitterionic ones. Black-Right-Pointing-Pointer Aurelin binds to DPC micelle surface with moderate affinity via two helical regions. -- Abstract: Aurelin is a 40-residue cationic antimicrobial peptide isolated from the mezoglea of a scyphoid jellyfish Aurelia aurita. Aurelin and its {sup 15}N-labeled analogue were overexpressed in Escherichiamore » coli and purified. Antimicrobial activity of the recombinant peptide was examined, and its spatial structure was studied by NMR spectroscopy. Aurelin represents a compact globule, enclosing one 3{sub 10}-helix and two {alpha}-helical regions cross-linked by three disulfide bonds. The peptide binds to anionic lipid (POPC/DOPG, 3:1) vesicles even at physiological salt concentration, it does not interact with zwitterionic (POPC) vesicles and interacts with the DPC micelle surface with moderate affinity via two {alpha}-helical regions. Although aurelin shows structural homology to the BgK and ShK toxins of sea anemones, its surface does not possess the 'functional dyad' required for the high-affinity interaction with the K{sup +}-channels. The obtained data permit to correlate the modest antibacterial properties and membrane activity of aurelin.« less

Weaving Knotted Vector Fields with Tunable Helicity.

PubMed

Kedia, Hridesh; Foster, David; Dennis, Mark R; Irvine, William T M

2016-12-30

We present a general construction of divergence-free knotted vector fields from complex scalar fields, whose closed field lines encode many kinds of knots and links, including torus knots, their cables, the figure-8 knot, and its generalizations. As finite-energy physical fields, they represent initial states for fields such as the magnetic field in a plasma, or the vorticity field in a fluid. We give a systematic procedure for calculating the vector potential, starting from complex scalar functions with knotted zero filaments, thus enabling an explicit computation of the helicity of these knotted fields. The construction can be used to generate isolated knotted flux tubes, filled by knots encoded in the lines of the vector field. Lastly, we give examples of manifestly knotted vector fields with vanishing helicity. Our results provide building blocks for analytical models and simulations alike.

Structural models of the MscL gating mechanism

NASA Technical Reports Server (NTRS)

Sukharev, S.; Durell, S. R.; Guy, H. R.

2001-01-01

Three-dimensional structural models of the mechanosensitive channel of large conductance, MscL, from the bacteria Mycobacterium tuberculosis and Escherichia coli were developed for closed, intermediate, and open conformations. The modeling began with the crystal structure of M. tuberculosis MscL, a homopentamer with two transmembrane alpha-helices, M1 and M2, per subunit. The first 12 N-terminal residues, not resolved in the crystal structure, were modeled as an amphipathic alpha-helix, called S1. A bundle of five parallel S1 helices are postulated to form a cytoplasmic gate. As membrane tension induces expansion, the tilts of M1 and M2 are postulated to increase as they move away from the axis of the pore. Substantial expansion is postulated to occur before the increased stress in the S1 to M1 linkers pulls the S1 bundle apart. During the opening transition, the S1 helices and C-terminus amphipathic alpha-helices, S3, are postulated to dock parallel to the membrane surface on the perimeter of the complex. The proposed gating mechanism reveals critical spatial relationships between the expandable transmembrane barrel formed by M1 and M2, the gate formed by S1 helices, and "strings" that link S1s to M1s. These models are consistent with numerous experimental results and modeling criteria.

Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations

PubMed Central

Baxa, Michael C.; Haddadian, Esmael J.; Jumper, John M.; Freed, Karl F.; Sosnick, Tobin R.

2014-01-01

The loss of conformational entropy is a major contribution in the thermodynamics of protein folding. However, accurate determination of the quantity has proven challenging. We calculate this loss using molecular dynamic simulations of both the native protein and a realistic denatured state ensemble. For ubiquitin, the total change in entropy is TΔSTotal = 1.4 kcal⋅mol−1 per residue at 300 K with only 20% from the loss of side-chain entropy. Our analysis exhibits mixed agreement with prior studies because of the use of more accurate ensembles and contributions from correlated motions. Buried side chains lose only a factor of 1.4 in the number of conformations available per rotamer upon folding (ΩU/ΩN). The entropy loss for helical and sheet residues differs due to the smaller motions of helical residues (TΔShelix−sheet = 0.5 kcal⋅mol−1), a property not fully reflected in the amide N-H and carbonyl C=O bond NMR order parameters. The results have implications for the thermodynamics of folding and binding, including estimates of solvent ordering and microscopic entropies obtained from NMR. PMID:25313044

Amylopectin molecular structure reflected in macromolecular organization of granular starch.

PubMed

Vermeylen, Rudi; Goderis, Bart; Reynaers, Harry; Delcour, Jan A

2004-01-01

For lintners with negligible amylose retrogradation, crystallinity related inversely to starch amylose content and, irrespective of starch source, incomplete removal of amorphous material was shown. The latter was more pronounced for B-type than for A-type starches. The two predominant lintner populations, with modal degrees of polymerization (DP) of 13-15 and 23-27, were best resolved for amylose-deficient and A-type starches. Results indicate a more specific hydrolysis of amorphous lamellae in such starches. Small-angle X-ray scattering showed a more intense 9-nm scattering peak for native amylose-deficient A-type starches than for their regular or B-type analogues. The experimental evidence indicates a lower contrasting density within the "crystalline" shells of the latter starches. A higher density in the amorphous lamellae, envisaged by the lamellar helical model, explains the relative acid resistance of linear amylopectin chains with DP > 20, observed in lintners of B-type starches. Because amylopectin chain length distributions were similar for regular and amylose-deficient starches of the same crystal type, we deduce that the more dense (and ordered) packing of double helices into lamellar structures in amylose-deficient starches is due to a different amylopectin branching pattern.

Local conformational dynamics in alpha-helices measured by fast triplet transfer.

PubMed

Fierz, Beat; Reiner, Andreas; Kiefhaber, Thomas

2009-01-27

Coupling fast triplet-triplet energy transfer (TTET) between xanthone and naphthylalanine to the helix-coil equilibrium in alanine-based peptides allowed the observation of local equilibrium fluctuations in alpha-helices on the nanoseconds to microseconds time scale. The experiments revealed faster helix unfolding in the terminal regions compared with the central parts of the helix with time constants varying from 250 ns to 1.4 micros at 5 degrees C. Local helix formation occurs with a time constant of approximately 400 ns, independent of the position in the helix. Comparing the experimental data with simulations using a kinetic Ising model showed that the experimentally observed dynamics can be explained by a 1-dimensional boundary diffusion with position-independent elementary time constants of approximately 50 ns for the addition and of approximately 65 ns for the removal of an alpha-helical segment. The elementary time constant for helix growth agrees well with previously measured time constants for formation of short loops in unfolded polypeptide chains, suggesting that helix elongation is mainly limited by a conformational search.

1D helical cadmium coordination polymers containing hydrazide ligand: The role of solvent and molar ratio

NASA Astrophysics Data System (ADS)

Notash, Behrouz

2018-03-01

Three new cadmium coordination polymers, [Cd(L)(NO3)2CH3OH]n, 1, {[Cd(L)2(NO3)]NO3}n, 2 and {[Cd(L)2(NO3)]NO3.H2O}n3, which L is nicotinohydrazide have been synthesized and characterized by spectroscopic methods as well as single crystal X-ray diffraction. Compounds 1-3 have been synthesized by changing solvent and metal-to-ligand ratio. X-ray crystallography showed that compounds 1-3 have different 1D helical structural motif. Semi-flexible nature of L ligand causes to syn-syn conformation which leading to form 1D helical chains coordination polymers. Compounds 2 and 3 were synthesized under the same reaction conditions with similar molar ratio, but using different solvent system. These compounds are pseudopolymorph which differs in the presence or absence of water molecule in their crystal packing. Hirshfeld surface analysis of the structures 1-3 have been performed and find the percent of participation of intermolecular interactions in the crystal packing of compounds.

Characterization of the geometry and topology of DNA pictured as a discrete collection of atoms

PubMed Central

Olson, Wilma K.

2014-01-01

The structural and physical properties of DNA are closely related to its geometry and topology. The classical mathematical treatment of DNA geometry and topology in terms of ideal smooth space curves was not designed to characterize the spatial arrangements of atoms found in high-resolution and simulated double-helical structures. We present here new and rigorous numerical methods for the rapid and accurate assessment of the geometry and topology of double-helical DNA structures in terms of the constituent atoms. These methods are well designed for large DNA datasets obtained in detailed numerical simulations or determined experimentally at high-resolution. We illustrate the usefulness of our methodology by applying it to the analysis of three canonical double-helical DNA chains, a 65-bp minicircle obtained in recent molecular dynamics simulations, and a crystallographic array of protein-bound DNA duplexes. Although we focus on fully base-paired DNA structures, our methods can be extended to treat the geometry and topology of melted DNA structures as well as to characterize the folding of arbitrary molecules such as RNA and cyclic peptides. PMID:24791158

Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter

NASA Astrophysics Data System (ADS)

Wang, Li-Ying; Ravi, Vidhya M.; Leblanc, Gérard; Padrós, Esteve; Cladera, Josep; Perálvarez-Marín, Alex

2016-09-01

Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes in some loops are followed by changes in the periplasm region of transmembrane helix 7. Helical curvature relaxation and unlocking of hydrophobic and ionic locks promote the outward opening of the transporter making accessible the substrate binding site. In particular, FRET studies on mutants of conserved aromatic residues of extracellular loop 4 showed lack of substrate binding, emphasizing the importance of this loop for making crucial interactions that control the opening of the periplasmic side. This study indicates that the alternate access mechanism for the melibiose transporter fits better into a flexible gating mechanism rather than the archetypical helical rigid-body rocker-switch mechanism.

Structural Basis for Substrate Fatty Acyl Chain Specificity

PubMed Central

McAndrew, Ryan P.; Wang, Yudong; Mohsen, Al-Walid; He, Miao; Vockley, Jerry; Kim, Jung-Ja P.

2008-01-01

Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a member of the family of acyl-CoA dehydrogenases (ACADs). Unlike the other ACADs, which are soluble homotetramers, VLCAD is a homodimer associated with the mitochondrial membrane. VLCAD also possesses an additional 180 residues in the C terminus that are not present in the other ACADs. We have determined the crystal structure of VLCAD complexed with myristoyl-CoA, obtained by co-crystallization, to 1.91-Å resolution. The overall fold of the N-terminal ∼400 residues of VLCAD is similar to that of the soluble ACADs including medium-chain acyl-CoA dehydrogenase (MCAD). The novel C-terminal domain forms an α-helical bundle that is positioned perpendicular to the two N-terminal helical domains. The fatty acyl moiety of the bound substrate/product is deeply imbedded inside the protein; however, the adenosine pyrophosphate portion of the C14-CoA ligand is disordered because of partial hydrolysis of the thioester bond and high mobility of the CoA moiety. The location of Glu-422 with respect to the C2-C3 of the bound ligand and FAD confirms Glu-422 to be the catalytic base. In MCAD, Gln-95 and Glu-99 form the base of the substrate binding cavity. In VLCAD, these residues are glycines (Gly-175 and Gly-178), allowing the binding channel to extend for an additional 12Å and permitting substrate acyl chain lengths as long as 24 carbons to bind. VLCAD deficiency is among the more common defects of mitochondrial β-oxidation and, if left undiagnosed, can be fatal. This structure allows us to gain insight into how a variant VLCAD genotype results in a clinical phenotype. PMID:18227065

Identifying the elusive link between amino acid sequence and charge selectivity in pentameric ligand-gated ion channels.

PubMed

Cymes, Gisela D; Grosman, Claudio

2016-10-10

Among neurotransmitter-gated ion channels, the superfamily of pentameric ligand-gated ion channels (pLGICs) is unique in that its members display opposite permeant-ion charge selectivities despite sharing the same structural fold. Although much effort has been devoted to the identification of the mechanism underlying the cation-versus-anion selectivity of these channels, a careful analysis of past work reveals that discrepancies exist, that different explanations for the same phenomenon have often been put forth, and that no consensus view has yet been reached. To elucidate the molecular basis of charge selectivity for the superfamily as a whole, we performed extensive mutagenesis and electrophysiological recordings on six different cation-selective and anion-selective homologs from vertebrate, invertebrate, and bacterial origin. We present compelling evidence for the critical involvement of ionized side chains-whether pore-facing or buried-rather than backbone atoms and propose a mechanism whereby not only their charge sign but also their conformation determines charge selectivity. Insertions, deletions, and residue-to-residue mutations involving nonionizable residues in the intracellular end of the pore seem to affect charge selectivity by changing the rotamer preferences of the ionized side chains in the first turn of the M2 α-helices. We also found that, upon neutralization of the charged residues in the first turn of M2, the control of charge selectivity is handed over to the many other ionized side chains that decorate the pore. This explains the long-standing puzzle as to why the neutralization of the intracellular-mouth glutamates affects charge selectivity to markedly different extents in different cation-selective pLGICs.

Microscopic artificial swimmers

NASA Astrophysics Data System (ADS)

Dreyfus, Rémi; Baudry, Jean; Roper, Marcus L.; Fermigier, Marc; Stone, Howard A.; Bibette, Jérôme

2005-10-01

Microorganisms such as bacteria and many eukaryotic cells propel themselves with hair-like structures known as flagella, which can exhibit a variety of structures and movement patterns. For example, bacterial flagella are helically shaped and driven at their bases by a reversible rotary engine, which rotates the attached flagellum to give a motion similar to that of a corkscrew. In contrast, eukaryotic cells use flagella that resemble elastic rods and exhibit a beating motion: internally generated stresses give rise to a series of bends that propagate towards the tip. In contrast to this variety of swimming strategies encountered in nature, a controlled swimming motion of artificial micrometre-sized structures has not yet been realized. Here we show that a linear chain of colloidal magnetic particles linked by DNA and attached to a red blood cell can act as a flexible artificial flagellum. The filament aligns with an external uniform magnetic field and is readily actuated by oscillating a transverse field. We find that the actuation induces a beating pattern that propels the structure, and that the external fields can be adjusted to control the velocity and the direction of motion.

Viscoplastic fracture transition of a biopolymer gel.

PubMed

Frieberg, Bradley R; Garatsa, Ray-Shimry; Jones, Ronald L; Bachert, John O; Crawshaw, Benjamin; Liu, X Michael; Chan, Edwin P

2018-06-13

Physical gels are swollen polymer networks consisting of transient crosslink junctions associated with hydrogen or ionic bonds. Unlike covalently crosslinked gels, these physical crosslinks are reversible thus enabling these materials to display highly tunable and dynamic mechanical properties. In this work, we study the polymer composition effects on the fracture behavior of a gelatin gel, which is a thermoreversible biopolymer gel consisting of denatured collagen chains bridging physical network junctions formed from triple helices. Below the critical volume fraction for chain entanglement, which we confirm via neutron scattering measurements, we find that the fracture behavior is consistent with a viscoplastic type process characterized by hydrodynamic friction of individual polymer chains through the polymer mesh to show that the enhancement in fracture scales inversely with the squared of the mesh size of the gelatin gel network. Above this critical volume fraction, the fracture process can be described by the Lake-Thomas theory that considers fracture as a chain scission process due to chain entanglements.

Structure of the starch granule--a curved crystal.

PubMed

Larsson, K

1991-09-01

A structure model of the molecular arrangement in native starch proposed earlier is further considered, with special regard to the lateral packing of cluster units. The amylopectin molecules are radially distributed, with branches concentrated in clusters. Within each cluster the polyglucan chains form double helices which are hexagonally packed. The clusters form spherically concentric crystalline layers with amylose in an amorphous form acting as a space-filler. A translational mechanism for the change of helical direction at boundaries between clusters is proposed which can account for variations in the curvature of the concentric layers. The model is related to X-ray diffraction data and optical birefringence, considering dissembly at gelatinization. The structure is also discussed in relation to biosynthesis. Some aspects of gelatinization, such as the recent glass-transition approach, are then considered.

Proline puckering parameters for collagen structure simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Di, E-mail: diwu@fudan.edu.cn

Collagen is made of triple helices rich in proline residues, and hence is influenced by the conformational motions of prolines. Because the backbone motions of prolines are restricted by the helical structures, the only side chain motion—proline puckering—becomes an influential factor that may affect the stability of collagen structures. In molecular simulations, a proper proline puckering population is desired so to yield valid results of the collagen properties. Here we design the proline puckering parameters in order to yield suitable proline puckering populations as demonstrated in the experimental results. We test these parameters in collagen and the proline dipeptide simulations.more » Compared with the results of the PDB and the quantum calculations, we propose the proline puckering parameters for the selected collagen model simulations.« less

Thermal transport dynamics in the quasi-single helicity state

NASA Astrophysics Data System (ADS)

McKinney, I. J.; Terry, P. W.

2017-06-01

A dynamical model describing oscillations between multiple and single helicity configurations in the quasi-single helicity (QSH) state of the reversed field pinch [P. W. Terry and G. G. Whelan, Plasma Phys. Controlled Fusion 56, 094003 (2014)] is extended to include electron temperature profile dynamics. It is shown that QSH dynamics is linked to the electron temperature profile because the suppression of mode coupling between tearing modes proposed to underlie QSH also suppresses magnetic-fluctuation-induced thermal transport. Above the threshold of dominant-mode shear that marks the transition to QSH, the model produces temperature-gradient steepening in the strong shear region. Oscillations of the dominant and secondary mode amplitudes give rise to oscillations of the temperature gradient. The phasing and amplitude of temperature gradient oscillations relative to those of the dominant mode are in agreement with experiment. This provides further evidence that the model, while heuristic, captures key physical aspects of the QSH state.

Single-molecule magnet behavior in an octanuclear dysprosium(iii) aggregate inherited from helical triangular Dy3 SMM-building blocks.

PubMed

Zhang, Li; Zhang, Peng; Zhao, Lang; Wu, Jianfeng; Guo, Mei; Tang, Jinkui

2016-06-28

An unprecedented octanuclear dysprosium(iii) cluster with the formula [Dy8L6(μ3-OH)4(μ2-CH3O)2(CH3OH)6(H2O)2]·6H2O·10CH3OH·2CH3CN () based on a nonlinearly tritopic aroylhydrazone ligand H3L has been isolated, realizing the successful linking of pairwise interesting triangular Dy3 SMMs. It is noteworthy that two enantiomers (Λ and Δ configurations) individually behaving as a coordination-induced chirality presented in the Dy3 helicate are connected in the meso Dy8 cluster. Remarkably, alternating-current magnetic susceptibility measurements revealed that the Dy8 cluster shows typical SMM behavior inherited from its Dy3 helical precursor. It is one of the rare polynuclear Lnn SMMs (n > 7) under zero dc field.

Effects of enterprise technology on supply chain collaboration: analysis of China-linked supply chain

NASA Astrophysics Data System (ADS)

Li, Ling

2012-02-01

Supply chain collaboration has received increasing attention from scholars and practitioners in recent years. However, our understanding of how enterprise information technology facilitates supply chain collaboration is still very limited, especially with regard to Chinese enterprise ownerships such as state-owned firms, joint-venture firms and local village-owned firms. This paper extends the theory established in enterprise information technology (IT) and supply chain collaboration literature and relates it with coordination in China-linked supply chain. Drawing upon an empirical study from 177 Chinese companies, we provide three major findings: (i) uncovered the importance of leveraging enterprise IT through supply chain collaboration; (ii) identified the relationship between enterprise ownership and enterprise technology use and supply chain collaboration in China-linked supply chain and (iii) illustrated effects of supply chain collaborative activities on operational and market performance.

Tracking polypeptide folds on the free energy surface: effects of the chain length and sequence.

PubMed

Brukhno, Andrey V; Ricchiuto, Piero; Auer, Stefan

2012-07-26

Characterization of the folding transition in polypeptides and assessing the thermodynamic stability of their structured folds are of primary importance for approaching the problem of protein folding. We use molecular dynamics simulations for a coarse grained polypeptide model in order to (1) obtain the equilibrium conformation diagram of homopolypeptides in a broad range of the chain lengths, N = 10, ..., 100, and temperatures, T (in a multicanonical ensemble), and (2) determine free energy profiles (FEPs) projected onto an optimal, so-called "natural", reaction coordinate that preserves the height of barriers and the diffusion coefficients on the underlying free energy hyper-surface. We then address the following fundamental questions. (i) How well does a kinetically determined free energy landscape of a single chain represent the polypeptide equilibrium (ensemble) behavior? In particular, under which conditions might the correspondence be lost, and what are the possible implications for the folding processes? (ii) How does the free energy landscape depend on the chain length (homopolypeptides) and the monomer interaction sequence (heteropolypeptides)? Our data reveal that at low T values equilibrium structures adopted by relatively short homopolypeptides (N < 60) are dominated by α-helical folds which correspond to the primary and secondary minima of the FEP. In contrast, longer homopolypeptides (N > 70), upon quasi-equilibrium cooling, fold preferentially in β-bundles with small helical portions, while the FEPs exhibit no distinct global minima. Moreover, subject to the choice of the initial configuration, at sufficiently low T, essentially metastable structures can be found and prevail far from the true thermodynamic equilibrium. We also show that, by sequence-enabling the polypeptide model, it is possible to restrict the chain to a very specific part of the configuration space, which results in substantial simplification and smoothing of the free energy landscape as compared to the case of the corresponding homopolypeptide.

Study of ordered hadron chains with the ATLAS detector

NASA Astrophysics Data System (ADS)

Aaboud, M.; Aad, G.; Abbott, B.; Abdinov, O.; Abeloos, B.; Abidi, S. H.; Abouzeid, O. S.; Abraham, N. L.; Abramowicz, H.; Abreu, H.; Abreu, R.; Abulaiti, Y.; Acharya, B. S.; Adachi, S.; Adamczyk, L.; Adelman, J.; Adersberger, M.; Adye, T.; Affolder, A. A.; Afik, Y.; Agatonovic-Jovin, T.; Agheorghiesei, C.; Aguilar-Saavedra, J. A.; Ahlen, S. P.; Ahmadov, F.; Aielli, G.; Akatsuka, S.; Akerstedt, H.; Åkesson, T. P. A.; Akilli, E.; Akimov, A. V.; Alberghi, G. L.; Albert, J.; Albicocco, P.; Alconada Verzini, M. J.; Alderweireldt, S. C.; Aleksa, M.; Aleksandrov, I. N.; Alexa, C.; Alexander, G.; Alexopoulos, T.; Alhroob, M.; Ali, B.; Aliev, M.; Alimonti, G.; Alison, J.; Alkire, S. P.; Allbrooke, B. M. M.; Allen, B. W.; Allport, P. P.; Aloisio, A.; Alonso, A.; Alonso, F.; Alpigiani, C.; Alshehri, A. A.; Alstaty, M. I.; Alvarez Gonzalez, B.; Álvarez Piqueras, D.; Alviggi, M. G.; Amadio, B. T.; Amaral Coutinho, Y.; Amelung, C.; Amidei, D.; Amor Dos Santos, S. P.; Amoroso, S.; Amundsen, G.; Anastopoulos, C.; Ancu, L. S.; Andari, N.; Andeen, T.; Anders, C. F.; Anders, J. K.; Anderson, K. J.; Andreazza, A.; Andrei, V.; Angelidakis, S.; Angelozzi, I.; Angerami, A.; Anisenkov, A. V.; Anjos, N.; Annovi, A.; Antel, C.; Antonelli, M.; Antonov, A.; Antrim, D. J.; Anulli, F.; Aoki, M.; Aperio Bella, L.; Arabidze, G.; Arai, Y.; Araque, J. P.; Araujo Ferraz, V.; Arce, A. T. H.; Ardell, R. E.; Arduh, F. A.; Arguin, J.-F.; Argyropoulos, S.; Arik, M.; Armbruster, A. J.; Armitage, L. J.; Arnaez, O.; Arnold, H.; Arratia, M.; Arslan, O.; Artamonov, A.; Artoni, G.; Artz, S.; Asai, S.; Asbah, N.; Ashkenazi, A.; Asquith, L.; Assamagan, K.; Astalos, R.; Atkinson, M.; Atlay, N. B.; Augsten, K.; Avolio, G.; Axen, B.; Ayoub, M. K.; Azuelos, G.; Baas, A. E.; Baca, M. J.; Bachacou, H.; Bachas, K.; Backes, M.; Bagnaia, P.; Bahmani, M.; Bahrasemani, H.; Baines, J. T.; Bajic, M.; Baker, O. K.; Baldin, E. M.; Balek, P.; Balli, F.; Balunas, W. K.; Banas, E.; Bandyopadhyay, A.; Banerjee, Sw.; Bannoura, A. A. E.; Barak, L.; Barberio, E. L.; Barberis, D.; Barbero, M.; Barillari, T.; Barisits, M.-S.; Barkeloo, J. T.; Barklow, T.; Barlow, N.; Barnes, S. L.; Barnett, B. M.; Barnett, R. M.; Barnovska-Blenessy, Z.; Baroncelli, A.; Barone, G.; Barr, A. J.; Barranco Navarro, L.; Barreiro, F.; Barreiro Guimarães da Costa, J.; Bartoldus, R.; Barton, A. E.; Bartos, P.; Basalaev, A.; Bassalat, A.; Bates, R. L.; Batista, S. J.; Batley, J. R.; Battaglia, M.; Bauce, M.; Bauer, F.; Bawa, H. S.; Beacham, J. B.; Beattie, M. D.; Beau, T.; Beauchemin, P. H.; Bechtle, P.; Beck, H. P.; Beck, H. C.; Becker, K.; Becker, M.; Becot, C.; Beddall, A. J.; Beddall, A.; Bednyakov, V. A.; Bedognetti, M.; Bee, C. P.; Beermann, T. A.; Begalli, M.; Begel, M.; Behr, J. K.; Bell, A. S.; Bella, G.; Bellagamba, L.; Bellerive, A.; Bellomo, M.; Belotskiy, K.; Beltramello, O.; Belyaev, N. L.; Benary, O.; Benchekroun, D.; Bender, M.; Bendtz, K.; Benekos, N.; Benhammou, Y.; Benhar Noccioli, E.; Benitez, J.; Benjamin, D. P.; Benoit, M.; Bensinger, J. R.; Bentvelsen, S.; Beresford, L.; Beretta, M.; Berge, D.; Bergeaas Kuutmann, E.; Berger, N.; Beringer, J.; Berlendis, S.; Bernard, N. R.; Bernardi, G.; Bernius, C.; Bernlochner, F. U.; Berry, T.; Berta, P.; Bertella, C.; Bertoli, G.; Bertolucci, F.; Bertram, I. A.; Bertsche, C.; Bertsche, D.; Besjes, G. J.; Bessidskaia Bylund, O.; Bessner, M.; Besson, N.; Betancourt, C.; Bethani, A.; Bethke, S.; Bevan, A. J.; Beyer, J.; Bianchi, R. M.; Biebel, O.; Biedermann, D.; Bielski, R.; Bierwagen, K.; Biesuz, N. V.; Biglietti, M.; Billoud, T. R. V.; Bilokon, H.; Bindi, M.; Bingul, A.; Bini, C.; Biondi, S.; Bisanz, T.; Bittrich, C.; Bjergaard, D. M.; Black, J. E.; Black, K. M.; Blair, R. E.; Blazek, T.; Bloch, I.; Blocker, C.; Blue, A.; Blum, W.; Blumenschein, U.; Blunier, S.; Bobbink, G. J.; Bobrovnikov, V. S.; Bocchetta, S. S.; Bocci, A.; Bock, C.; Boehler, M.; Boerner, D.; Bogavac, D.; Bogdanchikov, A. G.; Bohm, C.; Boisvert, V.; Bokan, P.; Bold, T.; Boldyrev, A. S.; Bolz, A. E.; Bomben, M.; Bona, M.; Boonekamp, M.; Borisov, A.; Borissov, G.; Bortfeldt, J.; Bortoletto, D.; Bortolotto, V.; Boscherini, D.; Bosman, M.; Bossio Sola, J. D.; Boudreau, J.; Bouffard, J.; Bouhova-Thacker, E. V.; Boumediene, D.; Bourdarios, C.; Boutle, S. K.; Boveia, A.; Boyd, J.; Boyko, I. R.; Bracinik, J.; Brandt, A.; Brandt, G.; Brandt, O.; Bratzler, U.; Brau, B.; Brau, J. E.; Breaden Madden, W. D.; Brendlinger, K.; Brennan, A. J.; Brenner, L.; Brenner, R.; Bressler, S.; Briglin, D. L.; Bristow, T. M.; Britton, D.; Britzger, D.; Brochu, F. M.; Brock, I.; Brock, R.; Brooijmans, G.; Brooks, T.; Brooks, W. K.; Brosamer, J.; Brost, E.; Broughton, J. H.; Bruckman de Renstrom, P. A.; Bruncko, D.; Bruni, A.; Bruni, G.; Bruni, L. S.; Brunt, Bh; Bruschi, M.; Bruscino, N.; Bryant, P.; Bryngemark, L.; Buanes, T.; Buat, Q.; Buchholz, P.; Buckley, A. G.; Budagov, I. A.; Buehrer, F.; Bugge, M. K.; Bulekov, O.; Bullock, D.; Burch, T. J.; Burdin, S.; Burgard, C. D.; Burger, A. M.; Burghgrave, B.; Burka, K.; Burke, S.; Burmeister, I.; Burr, J. T. P.; Busato, E.; Büscher, D.; Büscher, V.; Bussey, P.; Butler, J. M.; Buttar, C. M.; Butterworth, J. M.; Butti, P.; Buttinger, W.; Buzatu, A.; Buzykaev, A. R.; Cabrera Urbán, S.; Caforio, D.; Cairo, V. M.; Cakir, O.; Calace, N.; Calafiura, P.; Calandri, A.; Calderini, G.; Calfayan, P.; Callea, G.; Caloba, L. P.; Calvente Lopez, S.; Calvet, D.; Calvet, S.; Calvet, T. P.; Camacho Toro, R.; Camarda, S.; Camarri, P.; Cameron, D.; Caminal Armadans, R.; Camincher, C.; Campana, S.; Campanelli, M.; Camplani, A.; Campoverde, A.; Canale, V.; Cano Bret, M.; Cantero, J.; Cao, T.; Capeans Garrido, M. D. M.; Caprini, I.; Caprini, M.; Capua, M.; Carbone, R. M.; Cardarelli, R.; Cardillo, F.; Carli, I.; Carli, T.; Carlino, G.; Carlson, B. T.; Carminati, L.; Carney, R. M. D.; Caron, S.; Carquin, E.; Carrá, S.; Carrillo-Montoya, G. D.; Casadei, D.; Casado, M. P.; Casolino, M.; Casper, D. W.; Castelijn, R.; Castillo Gimenez, V.; Castro, N. F.; Catinaccio, A.; Catmore, J. R.; Cattai, A.; Caudron, J.; Cavaliere, V.; Cavallaro, E.; Cavalli, D.; Cavalli-Sforza, M.; Cavasinni, V.; Celebi, E.; Ceradini, F.; Cerda Alberich, L.; Cerqueira, A. S.; Cerri, A.; Cerrito, L.; Cerutti, F.; Cervelli, A.; Cetin, S. A.; Chafaq, A.; Chakraborty, D.; Chan, S. K.; Chan, W. S.; Chan, Y. L.; Chang, P.; Chapman, J. D.; Charlton, D. G.; Chau, C. C.; Chavez Barajas, C. A.; Che, S.; Cheatham, S.; Chegwidden, A.; Chekanov, S.; Chekulaev, S. V.; Chelkov, G. A.; Chelstowska, M. A.; Chen, C.; Chen, H.; Chen, J.; Chen, S.; Chen, S.; Chen, X.; Chen, Y.; Cheng, H. C.; Cheng, H. J.; Cheplakov, A.; Cheremushkina, E.; Cherkaoui El Moursli, R.; Cheu, E.; Cheung, K.; Chevalier, L.; Chiarella, V.; Chiarelli, G.; Chiodini, G.; Chisholm, A. S.; Chitan, A.; Chiu, Y. H.; Chizhov, M. V.; Choi, K.; Chomont, A. R.; Chouridou, S.; Chow, Y. S.; Christodoulou, V.; Chu, M. C.; Chudoba, J.; Chuinard, A. J.; Chwastowski, J. J.; Chytka, L.; Ciftci, A. K.; Cinca, D.; Cindro, V.; Cioara, I. A.; Ciocca, C.; Ciocio, A.; Cirotto, F.; Citron, Z. H.; Citterio, M.; Ciubancan, M.; Clark, A.; Clark, B. L.; Clark, M. R.; Clark, P. J.; Clarke, R. N.; Clement, C.; Coadou, Y.; Cobal, M.; Coccaro, A.; Cochran, J.; Colasurdo, L.; Cole, B.; Colijn, A. P.; Collot, J.; Colombo, T.; Conde Muiño, P.; Coniavitis, E.; Connell, S. H.; Connelly, I. A.; Constantinescu, S.; Conti, G.; Conventi, F.; Cooke, M.; Cooper-Sarkar, A. M.; Cormier, F.; Cormier, K. J. R.; Corradi, M.; Corriveau, F.; Cortes-Gonzalez, A.; Cortiana, G.; Costa, G.; Costa, M. J.; Costanzo, D.; Cottin, G.; Cowan, G.; Cox, B. E.; Cranmer, K.; Crawley, S. J.; Creager, R. A.; Cree, G.; Crépé-Renaudin, S.; Crescioli, F.; Cribbs, W. A.; Cristinziani, M.; Croft, V.; Crosetti, G.; Cueto, A.; Cuhadar Donszelmann, T.; Cukierman, A. R.; Cummings, J.; Curatolo, M.; Cúth, J.; Czekierda, S.; Czodrowski, P.; D'Amen, G.; D'Auria, S.; D'Eramo, L.; D'Onofrio, M.; da Cunha Sargedas de Sousa, M. J.; da Via, C.; Dabrowski, W.; Dado, T.; Dai, T.; Dale, O.; Dallaire, F.; Dallapiccola, C.; Dam, M.; Dandoy, J. R.; Daneri, M. F.; Dang, N. P.; Daniells, A. C.; Dann, N. S.; Danninger, M.; Dano Hoffmann, M.; Dao, V.; Darbo, G.; Darmora, S.; Dassoulas, J.; Dattagupta, A.; Daubney, T.; Davey, W.; David, C.; Davidek, T.; Davis, D. R.; Davison, P.; Dawe, E.; Dawson, I.; de, K.; de Asmundis, R.; de Benedetti, A.; de Castro, S.; de Cecco, S.; de Groot, N.; de Jong, P.; de la Torre, H.; de Lorenzi, F.; de Maria, A.; de Pedis, D.; de Salvo, A.; de Sanctis, U.; de Santo, A.; de Vasconcelos Corga, K.; de Vivie de Regie, J. B.; Debbe, R.; Debenedetti, C.; Dedovich, D. V.; Dehghanian, N.; Deigaard, I.; Del Gaudio, M.; Del Peso, J.; Delgove, D.; Deliot, F.; Delitzsch, C. M.; Dell'Acqua, A.; Dell'Asta, L.; Dell'Orso, M.; Della Pietra, M.; Della Volpe, D.; Delmastro, M.; Delporte, C.; Delsart, P. A.; Demarco, D. A.; Demers, S.; Demichev, M.; Demilly, A.; Denisov, S. P.; Denysiuk, D.; Derendarz, D.; Derkaoui, J. E.; Derue, F.; Dervan, P.; Desch, K.; Deterre, C.; Dette, K.; Devesa, M. R.; Deviveiros, P. O.; Dewhurst, A.; Dhaliwal, S.; di Bello, F. A.; di Ciaccio, A.; di Ciaccio, L.; di Clemente, W. K.; di Donato, C.; di Girolamo, A.; di Girolamo, B.; di Micco, B.; di Nardo, R.; di Petrillo, K. F.; di Simone, A.; di Sipio, R.; di Valentino, D.; Diaconu, C.; Diamond, M.; Dias, F. A.; Diaz, M. A.; Diehl, E. B.; Dietrich, J.; Díez Cornell, S.; Dimitrievska, A.; Dingfelder, J.; Dita, P.; Dita, S.; Dittus, F.; Djama, F.; Djobava, T.; Djuvsland, J. I.; Do Vale, M. A. 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T.; Mengarelli, A.; Menke, S.; Meoni, E.; Mergelmeyer, S.; Merlassino, C.; Mermod, P.; Merola, L.; Meroni, C.; Merritt, F. S.; Messina, A.; Metcalfe, J.; Mete, A. S.; Meyer, C.; Meyer, J.-P.; Meyer, J.; Meyer Zu Theenhausen, H.; Miano, F.; Middleton, R. P.; Miglioranzi, S.; Mijović, L.; Mikenberg, G.; Mikestikova, M.; Mikuž, M.; Milesi, M.; Milic, A.; Millar, D. A.; Miller, D. W.; Mills, C.; Milov, A.; Milstead, D. A.; Minaenko, A. A.; Minami, Y.; Minashvili, I. A.; Mincer, A. I.; Mindur, B.; Mineev, M.; Minegishi, Y.; Ming, Y.; Mir, L. M.; Mistry, K. P.; Mitani, T.; Mitrevski, J.; Mitsou, V. A.; Miucci, A.; Miyagawa, P. S.; Mizukami, A.; Mjörnmark, J. U.; Mkrtchyan, T.; Mlynarikova, M.; Moa, T.; Mochizuki, K.; Mogg, P.; Mohapatra, S.; Molander, S.; Moles-Valls, R.; Mondragon, M. C.; Mönig, K.; Monk, J.; Monnier, E.; Montalbano, A.; Montejo Berlingen, J.; Monticelli, F.; Monzani, S.; Moore, R. 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S.; Neumann, M.; Newman, P. R.; Ng, T. Y.; Nguyen Manh, T.; Nickerson, R. B.; Nicolaidou, R.; Nielsen, J.; Nikolaenko, V.; Nikolic-Audit, I.; Nikolopoulos, K.; Nilsen, J. K.; Nilsson, P.; Ninomiya, Y.; Nisati, A.; Nishu, N.; Nisius, R.; Nitsche, I.; Nitta, T.; Nobe, T.; Noguchi, Y.; Nomachi, M.; Nomidis, I.; Nomura, M. A.; Nooney, T.; Nordberg, M.; Norjoharuddeen, N.; Novgorodova, O.; Nowak, S.; Nozaki, M.; Nozka, L.; Ntekas, K.; Nurse, E.; Nuti, F.; O'Connor, K.; O'Neil, D. C.; O'Rourke, A. A.; O'Shea, V.; Oakham, F. G.; Oberlack, H.; Obermann, T.; Ocariz, J.; Ochi, A.; Ochoa, I.; Ochoa-Ricoux, J. P.; Oda, S.; Odaka, S.; Oh, A.; Oh, S. H.; Ohm, C. C.; Ohman, H.; Oide, H.; Okawa, H.; Okumura, Y.; Okuyama, T.; Olariu, A.; Oleiro Seabra, L. F.; Olivares Pino, S. A.; Oliveira Damazio, D.; Olszewski, A.; Olszowska, J.; Onofre, A.; Onogi, K.; Onyisi, P. U. E.; Oppen, H.; Oreglia, M. J.; Oren, Y.; Orestano, D.; Orlando, N.; Orr, R. S.; Osculati, B.; Ospanov, R.; Otero Y Garzon, G.; Otono, H.; Ouchrif, M.; Ould-Saada, F.; Ouraou, A.; Oussoren, K. P.; Ouyang, Q.; Owen, M.; Owen, R. E.; Ozcan, V. E.; Ozturk, N.; Pachal, K.; Pacheco Pages, A.; Pacheco Rodriguez, L.; Padilla Aranda, C.; Pagan Griso, S.; Paganini, M.; Paige, F.; Palacino, G.; Palazzo, S.; Palestini, S.; Palka, M.; Pallin, D.; Panagiotopoulou, E. St.; Panagoulias, I.; Pandini, C. E.; Panduro Vazquez, J. G.; Pani, P.; Panitkin, S.; Pantea, D.; Paolozzi, L.; Papadopoulou, Th. D.; Papageorgiou, K.; Paramonov, A.; Paredes Hernandez, D.; Parker, A. J.; Parker, M. A.; Parker, K. A.; Parodi, F.; Parsons, J. A.; Parzefall, U.; Pascuzzi, V. R.; Pasner, J. M.; Pasqualucci, E.; Passaggio, S.; Pastore, Fr.; Pataraia, S.; Pater, J. R.; Pauly, T.; Pearson, B.; Pedraza Lopez, S.; Pedro, R.; Peleganchuk, S. V.; Penc, O.; Peng, C.; Peng, H.; Penwell, J.; Peralva, B. S.; Perego, M. M.; Perepelitsa, D. V.; Peri, F.; Perini, L.; Pernegger, H.; Perrella, S.; Peschke, R.; Peshekhonov, V. D.; Peters, K.; Peters, R. F. Y.; Petersen, B. A.; Petersen, T. C.; Petit, E.; Petridis, A.; Petridou, C.; Petroff, P.; Petrolo, E.; Petrov, M.; Petrucci, F.; Pettersson, N. E.; Peyaud, A.; Pezoa, R.; Phillips, F. H.; Phillips, P. W.; Piacquadio, G.; Pianori, E.; Picazio, A.; Piccaro, E.; Pickering, M. A.; Piegaia, R.; Pilcher, J. E.; Pilkington, A. D.; Pin, A. W. J.; Pinamonti, M.; Pinfold, J. L.; Pirumov, H.; Pitt, M.; Plazak, L.; Pleier, M.-A.; Pleskot, V.; Plotnikova, E.; Pluth, D.; Podberezko, P.; Poettgen, R.; Poggi, R.; Poggioli, L.; Pogrebnyak, I.; Pohl, D.; Polesello, G.; Poley, A.; Policicchio, A.; Polifka, R.; Polini, A.; Pollard, C. S.; Polychronakos, V.; Pommès, K.; Ponomarenko, D.; Pontecorvo, L.; Popeneciu, G. A.; Pospisil, S.; Potamianos, K.; Potrap, I. N.; Potter, C. J.; Poulsen, T.; Poveda, J.; Pozo Astigarraga, M. 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A.; Scheirich, D.; Schernau, M.; Schiavi, C.; Schier, S.; Schildgen, L. K.; Schillo, C.; Schioppa, M.; Schlenker, S.; Schmidt-Sommerfeld, K. R.; Schmieden, K.; Schmitt, C.; Schmitt, S.; Schmitz, S.; Schnoor, U.; Schoeffel, L.; Schoening, A.; Schoenrock, B. D.; Schopf, E.; Schott, M.; Schouwenberg, J. F. P.; Schovancova, J.; Schramm, S.; Schuh, N.; Schulte, A.; Schultens, M. J.; Schultz-Coulon, H.-C.; Schulz, H.; Schumacher, M.; Schumm, B. A.; Schune, Ph.; Schwartzman, A.; Schwarz, T. A.; Schweiger, H.; Schwemling, Ph.; Schwienhorst, R.; Schwindling, J.; Sciandra, A.; Sciolla, G.; Scornajenghi, M.; Scuri, F.; Scutti, F.; Searcy, J.; Seema, P.; Seidel, S. C.; Seiden, A.; Seixas, J. M.; Sekhniaidze, G.; Sekhon, K.; Sekula, S. J.; Semprini-Cesari, N.; Senkin, S.; Serfon, C.; Serin, L.; Serkin, L.; Sessa, M.; Seuster, R.; Severini, H.; Sfiligoj, T.; Sforza, F.; Sfyrla, A.; Shabalina, E.; Shaikh, N. W.; Shan, L. Y.; Shang, R.; Shank, J. T.; Shapiro, M.; Shatalov, P. B.; Shaw, K.; Shaw, S. M.; Shcherbakova, A.; Shehu, C. Y.; Shen, Y.; Sherafati, N.; Sherwood, P.; Shi, L.; Shimizu, S.; Shimmin, C. O.; Shimojima, M.; Shipsey, I. P. J.; Shirabe, S.; Shiyakova, M.; Shlomi, J.; Shmeleva, A.; Shoaleh Saadi, D.; Shochet, M. J.; Shojaii, S.; Shope, D. R.; Shrestha, S.; Shulga, E.; Shupe, M. A.; Sicho, P.; Sickles, A. M.; Sidebo, P. E.; Sideras Haddad, E.; Sidiropoulou, O.; Sidoti, A.; Siegert, F.; Sijacki, Dj.; Silva, J.; Silverstein, S. B.; Simak, V.; Simic, Lj.; Simion, S.; Simioni, E.; Simmons, B.; Simon, M.; Sinervo, P.; Sinev, N. B.; Sioli, M.; Siragusa, G.; Siral, I.; Sivoklokov, S. Yu.; Sjölin, J.; Skinner, M. B.; Skubic, P.; Slater, M.; Slavicek, T.; Slawinska, M.; Sliwa, K.; Slovak, R.; Smakhtin, V.; Smart, B. H.; Smiesko, J.; Smirnov, N.; Smirnov, S. Yu.; Smirnov, Y.; Smirnova, L. N.; Smirnova, O.; Smith, J. W.; Smith, M. N. K.; Smith, R. W.; Smizanska, M.; Smolek, K.; Snesarev, A. A.; Snyder, I. M.; Snyder, S.; Sobie, R.; Socher, F.; Soffer, A.; Søgaard, A.; Soh, D. A.; Sokhrannyi, G.; Solans Sanchez, C. A.; Solar, M.; Soldatov, E. Yu.; Soldevila, U.; Solodkov, A. A.; Soloshenko, A.; Solovyanov, O. V.; Solovyev, V.; Sommer, P.; Son, H.; Sopczak, A.; Sosa, D.; Sotiropoulou, C. L.; Soualah, R.; Soukharev, A. M.; South, D.; Sowden, B. C.; Spagnolo, S.; Spalla, M.; Spangenberg, M.; Spanò, F.; Sperlich, D.; Spettel, F.; Spieker, T. M.; Spighi, R.; Spigo, G.; Spiller, L. A.; Spousta, M.; St. Denis, R. D.; Stabile, A.; Stamen, R.; Stamm, S.; Stanecka, E.; Stanek, R. W.; Stanescu, C.; Stanitzki, M. M.; Stapf, B. S.; Stapnes, S.; Starchenko, E. A.; Stark, G. H.; Stark, J.; Stark, S. H.; Staroba, P.; Starovoitov, P.; Stärz, S.; Staszewski, R.; Steinberg, P.; Stelzer, B.; Stelzer, H. J.; Stelzer-Chilton, O.; Stenzel, H.; Stewart, G. A.; Stockton, M. C.; Stoebe, M.; Stoicea, G.; Stolte, P.; Stonjek, S.; Stradling, A. R.; Straessner, A.; Stramaglia, M. E.; Strandberg, J.; Strandberg, S.; Strauss, M.; Strizenec, P.; Ströhmer, R.; Strom, D. M.; Stroynowski, R.; Strubig, A.; Stucci, S. A.; Stugu, B.; Styles, N. A.; Su, D.; Su, J.; Suchek, S.; Sugaya, Y.; Suk, M.; Sulin, V. V.; Sultan, Dms; Sultansoy, S.; Sumida, T.; Sun, S.; Sun, X.; Suruliz, K.; Suster, C. J. E.; Sutton, M. R.; Suzuki, S.; Svatos, M.; Swiatlowski, M.; Swift, S. P.; Sykora, I.; Sykora, T.; Ta, D.; Tackmann, K.; Taenzer, J.; Taffard, A.; Tafirout, R.; Tahirovic, E.; Taiblum, N.; Takai, H.; Takashima, R.; Takasugi, E. H.; Takeshita, T.; Takubo, Y.; Talby, M.; Talyshev, A. A.; Tanaka, J.; Tanaka, M.; Tanaka, R.; Tanaka, S.; Tanioka, R.; Tannenwald, B. B.; Tapia Araya, S.; Tapprogge, S.; Tarem, S.; Tartarelli, G. F.; Tas, P.; Tasevsky, M.; Tashiro, T.; Tassi, E.; Tavares Delgado, A.; Tayalati, Y.; Taylor, A. C.; Taylor, A. J.; Taylor, G. N.; Taylor, P. T. E.; Taylor, W.; Teixeira-Dias, P.; Temple, D.; Ten Kate, H.; Teng, P. K.; Teoh, J. J.; Tepel, F.; Terada, S.; Terashi, K.; Terron, J.; Terzo, S.; Testa, M.; Teuscher, R. J.; Theveneaux-Pelzer, T.; Thiele, F.; Thomas, J. P.; Thomas-Wilsker, J.; Thompson, P. D.; Thompson, A. S.; Thomsen, L. A.; Thomson, E.; Tibbetts, M. J.; Ticse Torres, R. E.; Tikhomirov, V. O.; Tikhonov, Yu. A.; Timoshenko, S.; Tipton, P.; Tisserant, S.; Todome, K.; Todorova-Nova, S.; Todt, S.; Tojo, J.; Tokár, S.; Tokushuku, K.; Tolley, E.; Tomlinson, L.; Tomoto, M.; Tompkins, L.; Toms, K.; Tong, B.; Tornambe, P.; Torrence, E.; Torres, H.; Torró Pastor, E.; Toth, J.; Touchard, F.; Tovey, D. R.; Treado, C. J.; Trefzger, T.; Tresoldi, F.; Tricoli, A.; Trigger, I. M.; Trincaz-Duvoid, S.; Tripiana, M. F.; Trischuk, W.; Trocmé, B.; Trofymov, A.; Troncon, C.; Trottier-McDonald, M.; Trovatelli, M.; Truong, L.; Trzebinski, M.; Trzupek, A.; Tsang, K. W.; Tseng, J. C.-L.; Tsiareshka, P. V.; Tsipolitis, G.; Tsirintanis, N.; Tsiskaridze, S.; Tsiskaridze, V.; Tskhadadze, E. G.; Tsui, K. M.; Tsukerman, I. I.; Tsulaia, V.; Tsuno, S.; Tsybychev, D.; Tu, Y.; Tudorache, A.; Tudorache, V.; Tulbure, T. T.; Tuna, A. N.; Tupputi, S. A.; Turchikhin, S.; Turgeman, D.; Turk Cakir, I.; Turra, R.; Tuts, P. M.; Ucchielli, G.; Ueda, I.; Ughetto, M.; Ukegawa, F.; Unal, G.; Undrus, A.; Unel, G.; Ungaro, F. C.; Unno, Y.; Unverdorben, C.; Urban, J.; Urquijo, P.; Urrejola, P.; Usai, G.; Usui, J.; Vacavant, L.; Vacek, V.; Vachon, B.; Vadla, K. O. H.; Vaidya, A.; Valderanis, C.; Valdes Santurio, E.; Valente, M.; Valentinetti, S.; Valero, A.; Valéry, L.; Valkar, S.; Vallier, A.; Valls Ferrer, J. A.; van den Wollenberg, W.; van der Graaf, H.; van Gemmeren, P.; van Nieuwkoop, J.; van Vulpen, I.; van Woerden, M. C.; Vanadia, M.; Vandelli, W.; Vaniachine, A.; Vankov, P.; Vardanyan, G.; Vari, R.; Varnes, E. W.; Varni, C.; Varol, T.; Varouchas, D.; Vartapetian, A.; Varvell, K. E.; Vasquez, J. G.; Vasquez, G. A.; Vazeille, F.; Vazquez Schroeder, T.; Veatch, J.; Veeraraghavan, V.; Veloce, L. M.; Veloso, F.; Veneziano, S.; Ventura, A.; Venturi, M.; Venturi, N.; Venturini, A.; Vercesi, V.; Verducci, M.; Verkerke, W.; Vermeulen, A. T.; Vermeulen, J. C.; Vetterli, M. C.; Viaux Maira, N.; Viazlo, O.; Vichou, I.; Vickey, T.; Vickey Boeriu, O. E.; Viehhauser, G. H. A.; Viel, S.; Vigani, L.; Villa, M.; Villaplana Perez, M.; Vilucchi, E.; Vincter, M. G.; Vinogradov, V. B.; Vishwakarma, A.; Vittori, C.; Vivarelli, I.; Vlachos, S.; Vogel, M.; Vokac, P.; Volpi, G.; von der Schmitt, H.; von Toerne, E.; Vorobel, V.; Vorobev, K.; Vos, M.; Voss, R.; Vossebeld, J. H.; Vranjes, N.; Vranjes Milosavljevic, M.; Vrba, V.; Vreeswijk, M.; Vuillermet, R.; Vukotic, I.; Wagner, P.; Wagner, W.; Wagner-Kuhr, J.; Wahlberg, H.; Wahrmund, S.; Walder, J.; Walker, R.; Walkowiak, W.; Wallangen, V.; Wang, C.; Wang, C.; Wang, F.; Wang, H.; Wang, H.; Wang, J.; Wang, J.; Wang, Q.; Wang, R.; Wang, S. M.; Wang, T.; Wang, W.; Wang, W.; Wang, Z.; Wanotayaroj, C.; Warburton, A.; Ward, C. P.; Wardrope, D. R.; Washbrook, A.; Watkins, P. M.; Watson, A. T.; Watson, M. F.; Watts, G.; Watts, S.; Waugh, B. M.; Webb, A. F.; Webb, S.; Weber, M. S.; Weber, S. W.; Weber, S. A.; Webster, J. S.; Weidberg, A. R.; Weinert, B.; Weingarten, J.; Weirich, M.; Weiser, C.; Weits, H.; Wells, P. S.; Wenaus, T.; Wengler, T.; Wenig, S.; Wermes, N.; Werner, M. D.; Werner, P.; Wessels, M.; Weston, T. D.; Whalen, K.; Whallon, N. L.; Wharton, A. M.; White, A. S.; White, A.; White, M. J.; White, R.; Whiteson, D.; Whitmore, B. W.; Wickens, F. J.; Wiedenmann, W.; Wielers, M.; Wiglesworth, C.; Wiik-Fuchs, L. A. M.; Wildauer, A.; Wilk, F.; Wilkens, H. G.; Williams, H. H.; Williams, S.; Willis, C.; Willocq, S.; Wilson, J. A.; Wingerter-Seez, I.; Winkels, E.; Winklmeier, F.; Winston, O. J.; Winter, B. T.; Wittgen, M.; Wobisch, M.; Wolf, T. M. H.; Wolff, R.; Wolter, M. W.; Wolters, H.; Wong, V. W. S.; Worm, S. D.; Wosiek, B. K.; Wotschack, J.; Wozniak, K. W.; Wu, M.; Wu, S. L.; Wu, X.; Wu, Y.; Wyatt, T. R.; Wynne, B. M.; Xella, S.; Xi, Z.; Xia, L.; Xu, D.; Xu, L.; Xu, T.; Yabsley, B.; Yacoob, S.; Yamaguchi, D.; Yamaguchi, Y.; Yamamoto, A.; Yamamoto, S.; Yamanaka, T.; Yamane, F.; Yamatani, M.; Yamazaki, Y.; Yan, Z.; Yang, H.; Yang, H.; Yang, Y.; Yang, Z.; Yao, W.-M.; Yap, Y. C.; Yasu, Y.; Yatsenko, E.; Yau Wong, K. H.; Ye, J.; Ye, S.; Yeletskikh, I.; Yigitbasi, E.; Yildirim, E.; Yorita, K.; Yoshihara, K.; Young, C.; Young, C. J. S.; Yu, J.; Yu, J.; Yuen, S. P. Y.; Yusuff, I.; Zabinski, B.; Zacharis, G.; Zaidan, R.; Zaitsev, A. M.; Zakharchuk, N.; Zalieckas, J.; Zaman, A.; Zambito, S.; Zanzi, D.; Zeitnitz, C.; Zemaityte, G.; Zemla, A.; Zeng, J. C.; Zeng, Q.; Zenin, O.; Ženiš, T.; Zerwas, D.; Zhang, D.; Zhang, F.; Zhang, G.; Zhang, H.; Zhang, J.; Zhang, L.; Zhang, L.; Zhang, M.; Zhang, P.; Zhang, R.; Zhang, R.; Zhang, X.; Zhang, Y.; Zhang, Z.; Zhao, X.; Zhao, Y.; Zhao, Z.; Zhemchugov, A.; Zhou, B.; Zhou, C.; Zhou, L.; Zhou, M.; Zhou, M.; Zhou, N.; Zhu, C. G.; Zhu, H.; Zhu, J.; Zhu, Y.; Zhuang, X.; Zhukov, K.; Zibell, A.; Zieminska, D.; Zimine, N. I.; Zimmermann, C.; Zimmermann, S.; Zinonos, Z.; Zinser, M.; Ziolkowski, M.; Živković, L.; Zobernig, G.; Zoccoli, A.; Zou, R.; Zur Nedden, M.; Zwalinski, L.; Atlas Collaboration

2017-11-01

The analysis of the momentum difference between charged hadrons in high-energy proton-proton collisions is performed in order to study coherent particle production. The observed correlation pattern agrees with a model of a helical QCD string fragmenting into a chain of ground-state hadrons. A threshold momentum difference in the production of adjacent pairs of charged hadrons is observed, in agreement with model predictions. The presence of low-mass hadron chains also explains the emergence of charge-combination-dependent two-particle correlations commonly attributed to Bose-Einstein interference. The data sample consists of 190 μ b-1 of minimum-bias events collected with proton-proton collisions at a center-of-mass energy √{s }=7 TeV in the early low-luminosity data taking with the ATLAS detector at the LHC.

Wormlike Chain Theory and Bending of Short DNA

NASA Astrophysics Data System (ADS)

Mazur, Alexey K.

2007-05-01

The probability distributions for bending angles in double helical DNA obtained in all-atom molecular dynamics simulations are compared with theoretical predictions. The computed distributions remarkably agree with the wormlike chain theory and qualitatively differ from predictions of the subelastic chain model. The computed data exhibit only small anomalies in the apparent flexibility of short DNA and cannot account for the recently reported AFM data. It is possible that the current atomistic DNA models miss some essential mechanisms of DNA bending on intermediate length scales. Analysis of bent DNA structures reveal, however, that the bending motion is structurally heterogeneous and directionally anisotropic on the length scales where the experimental anomalies were detected. These effects are essential for interpretation of the experimental data and they also can be responsible for the apparent discrepancy.

Influence of ionic liquids on the syntheses and structures of Mn(II) coordination polymers based on multidentate N-heterocyclic aromatic ligands and bridging carboxylate ligands.

PubMed

Qin, Jian-Hua; Wang, Hua-Rui; Pan, Qi; Zang, Shuang-Quan; Hou, Hongwei; Fan, Yaoting

2015-10-28

Seven Mn(ii) coordination polymers, namely {[Mn2(ptptp)Cl2(H2O)3]·H2O}n (1), {[Mn(μ-ptptp)3]2[Mn3(μ3-Cl)]2}·2Cl·16H2O (2), {[Mn2(ptptp)(ip)2(H2O)3]·H2O}n (3), {[Mn2(ptptp)(5-CH3-ip)2(H2O)3]·H2O}n (4), {[Mn4(ptptp)(5-Br-ip)3(H2O)3]·4H2O}n (5), {[Mn2(ptptp)(Hbtc)(H2O)2]·2H2O}n (6) and {[Mn2(ptptp)(tdc)(H2O)2]·1.5H2O}n (7), have been prepared based on multidentate N-heterocyclic aromatic ligands and bridging carboxylate ligands (H2ptptp = 2-(5-{6-[5-(pyrazin-2-yl)-1H-1,2,4-triazol-3-yl]pyridin-2-yl}-1H-1,2,4-triazol-3-yl)pyrazine; R-isophthalic acids, H2ip-R: R = -H (3), -CH3 (4), -Br (5); H3btc = trimesic acid (6); H2tdc = thiophene-2,5-dicarboxylic acid (7)), in order to further probe the multiple roles of [RMI]Br ionic liquids in the hydro/solvothermal synthesis (RMI = 1-alkyl-3-methylimidazolium, R = ethyl, or propyl, or butyl). The successful syntheses of complexes 2-6 suggest that in hydro/solvothermal synthesis the addition of a small amount of [RMI]Br plays a crucial role. Complex 1 exhibits single right-handed helices constructed by ptptp ligands and Mn(ii) ions. Complex 2 possesses octanuclear helicate structures in which two propeller-shaped [Mn(μ-ptptp)3](4-) units embrace two [Mn3(μ3-Cl)](5+) cluster cores inside. Complexes 3 and 4 are isostructural and display a 1D double chain formed by two kinds of pseudo meso-helices: (Mn-ptptp)n and (Mn-5-R-ip)n. Complex 5 has a 2D structure containing 1D Mn(ii) ion chains formed through carboxylates and [ptptp](2-)-N,N bridges. Complex 6 shows a 2D structure formed by a meso-helix (Mn-ptptp)n and the partly deprotonated Hbtc ligands. Complex 7 features a heterochiral [2 + 2] coaxially nested double-helical column formed by using the outer double-helices (Mn-ptptp)n as a template to encapsulate the inner double-helices (Mn-tdc)n with opposite orientation. All complexes were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, single-crystal X-ray crystallography and powder X-ray diffraction. The magnetic properties of 1-7 were also investigated.

Accurate determination of interfacial protein secondary structure by combining interfacial-sensitive amide I and amide III spectral signals.

PubMed

Ye, Shuji; Li, Hongchun; Yang, Weilai; Luo, Yi

2014-01-29

Accurate determination of protein structures at the interface is essential to understand the nature of interfacial protein interactions, but it can only be done with a few, very limited experimental methods. Here, we demonstrate for the first time that sum frequency generation vibrational spectroscopy can unambiguously differentiate the interfacial protein secondary structures by combining surface-sensitive amide I and amide III spectral signals. This combination offers a powerful tool to directly distinguish random-coil (disordered) and α-helical structures in proteins. From a systematic study on the interactions between several antimicrobial peptides (including LKα14, mastoparan X, cecropin P1, melittin, and pardaxin) and lipid bilayers, it is found that the spectral profiles of the random-coil and α-helical structures are well separated in the amide III spectra, appearing below and above 1260 cm(-1), respectively. For the peptides with a straight backbone chain, the strength ratio for the peaks of the random-coil and α-helical structures shows a distinct linear relationship with the fraction of the disordered structure deduced from independent NMR experiments reported in the literature. It is revealed that increasing the fraction of negatively charged lipids can induce a conformational change of pardaxin from random-coil to α-helical structures. This experimental protocol can be employed for determining the interfacial protein secondary structures and dynamics in situ and in real time without extraneous labels.

Energy hyperspace for stacking interaction in AU/AU dinucleotide step: Dispersion-corrected density functional theory study.

PubMed

Mukherjee, Sanchita; Kailasam, Senthilkumar; Bansal, Manju; Bhattacharyya, Dhananjay

2014-01-01

Double helical structures of DNA and RNA are mostly determined by base pair stacking interactions, which give them the base sequence-directed features, such as small roll values for the purine-pyrimidine steps. Earlier attempts to characterize stacking interactions were mostly restricted to calculations on fiber diffraction geometries or optimized structure using ab initio calculations lacking variation in geometry to comment on rather unusual large roll values observed in AU/AU base pair step in crystal structures of RNA double helices. We have generated stacking energy hyperspace by modeling geometries with variations along the important degrees of freedom, roll, and slide, which were chosen via statistical analysis as maximally sequence dependent. Corresponding energy contours were constructed by several quantum chemical methods including dispersion corrections. This analysis established the most suitable methods for stacked base pair systems despite the limitation imparted by number of atom in a base pair step to employ very high level of theory. All the methods predict negative roll value and near-zero slide to be most favorable for the purine-pyrimidine steps, in agreement with Calladine's steric clash based rule. Successive base pairs in RNA are always linked by sugar-phosphate backbone with C3'-endo sugars and this demands C1'-C1' distance of about 5.4 Å along the chains. Consideration of an energy penalty term for deviation of C1'-C1' distance from the mean value, to the recent DFT-D functionals, specifically ωB97X-D appears to predict reliable energy contour for AU/AU step. Such distance-based penalty improves energy contours for the other purine-pyrimidine sequences also. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 107-120, 2014. Copyright © 2013 Wiley Periodicals, Inc.

Stick-slip nanofriction in cold-ion traps

NASA Astrophysics Data System (ADS)

Mandelli, Davide; Vanossi, Andrea; Tosatti, Erio

2013-03-01

Trapped cold ions are known to form linear or planar zigzag chains, helices or clusters depending on trapping conditions. They may be forced to slide over a laser induced corrugated potential, a mimick of sliding friction. We present MD simulations of an incommensurate 101 ions chain sliding subject to an external electric field. As expected with increasing corrugation, we observe the transition from a smooth-sliding, highly lubric regime to a strongly dissipative stick-slip regime. Owing to inhomogeneity the dynamics shows features reminiscent of macroscopic frictional behaviors. While the chain extremities are pinned, the incommensurate central part is initially free to slide. The onset of global sliding is preceded by precursor events consisting of partial slips of chain portions further from the center. We also look for frictional anomalies expected for the chain sliding across the linear-zigzag structural phase transition. Although the chain is too short for a proper critical behavior, the sliding friction displays a frank rise near the transition, due to opening of a new dissipative channel via excitations of transverse modes. Research partly sponsored by Sinergia Project CRSII2 136287/1.

Packing C60 in Boron Nitride Nanotubes

NASA Astrophysics Data System (ADS)

Mickelson, W.; Aloni, S.; Han, Wei-Qiang; Cumings, John; Zettl, A.

2003-04-01

We have created insulated C60 nanowire by packing C60 molecules into the interior of insulating boron nitride nanotubes (BNNTs). For small-diameter BNNTs, the wire consists of a linear chain of C60 molecules. With increasing BNNT inner diameter, unusual C60 stacking configurations are obtained (including helical, hollow core, and incommensurate) that are unknown for bulk or thin-film forms of C60. C60 in BNNTs thus presents a model system for studying the properties of dimensionally constrained ``silo'' crystal structures. For the linear-chain case, we have fused the C60 molecules to form a single-walled carbon nanotube inside the insulating BNNT.

'Boomerang'-like insertion of a fusogenic peptide in a lipid membrane revealed by solid-state 19F NMR.

PubMed

Afonin, Sergii; Dürr, Ulrich H N; Glaser, Ralf W; Ulrich, Anne S

2004-02-01

Solid state (19)F NMR revealed the conformation and alignment of the fusogenic peptide sequence B18 from the sea urchin fertilization protein bindin embedded in flat phospholipid bilayers. Single (19)F labels were introduced into nine distinct positions along the wild-type sequence by substituting each hydrophobic amino acid, one by one, with L-4-fluorophenylglycine. Their anisotropic chemical shifts were measured in uniaxially oriented membrane samples and used as orientational constraints to model the peptide structure in the membrane-bound state. Previous (1)H NMR studies of B18 in 30% TFE and in detergent micelles had shown that the peptide structure consists of two alpha-helical segments that are connected by a flexible hinge. This helix-break-helix motif was confirmed here by the solid-state (19)F NMR data, while no other secondary structure (beta-sheet, 3(10)-helix) was compatible with the set of orientational constraints. For both alpha-helical segments we found that the helical conformation extends all the way to the respective N- and C-termini of the peptide. Analysis of the corresponding tilt and azimuthal rotation angles showed that the N-terminal helix of B18 is immersed obliquely into the bilayer (at a tilt angle tau approximately 54 degrees), whereas the C-terminus is peripherally aligned (tau approximately 91 degrees). The azimuthal orientation of the two segments is consistent with the amphiphilic distribution of side-chains. The observed 'boomerang'-like mode of insertion into the membrane may thus explain how peptide binding leads to lipid dehydration and acyl chain perturbation as a prerequisite for bilayer fusion to occur. Copyright 2004 John Wiley & Sons, Ltd.

Macromolecular ab initio phasing enforcing secondary and tertiary structure.

PubMed

Millán, Claudia; Sammito, Massimo; Usón, Isabel

2015-01-01

Ab initio phasing of macromolecular structures, from the native intensities alone with no experimental phase information or previous particular structural knowledge, has been the object of a long quest, limited by two main barriers: structure size and resolution of the data. Current approaches to extend the scope of ab initio phasing include use of the Patterson function, density modification and data extrapolation. The authors' approach relies on the combination of locating model fragments such as polyalanine α-helices with the program PHASER and density modification with the program SHELXE. Given the difficulties in discriminating correct small substructures, many putative groups of fragments have to be tested in parallel; thus calculations are performed in a grid or supercomputer. The method has been named after the Italian painter Arcimboldo, who used to compose portraits out of fruit and vegetables. With ARCIMBOLDO, most collections of fragments remain a 'still-life', but some are correct enough for density modification and main-chain tracing to reveal the protein's true portrait. Beyond α-helices, other fragments can be exploited in an analogous way: libraries of helices with modelled side chains, β-strands, predictable fragments such as DNA-binding folds or fragments selected from distant homologues up to libraries of small local folds that are used to enforce nonspecific tertiary structure; thus restoring the ab initio nature of the method. Using these methods, a number of unknown macromolecules with a few thousand atoms and resolutions around 2 Å have been solved. In the 2014 release, use of the program has been simplified. The software mediates the use of massive computing to automate the grid access required in difficult cases but may also run on a single multicore workstation (http://chango.ibmb.csic.es/ARCIMBOLDO_LITE) to solve straightforward cases.

Human disease mortality kinetics are explored through a chain model embodying principles of extreme value theory and competing risks.

PubMed

Juckett, D A; Rosenberg, B

1992-04-21

The distributions for human disease-specific mortality exhibit two striking characteristics: survivorship curves that intersect near the longevity limit; and, the clustering of best-fitting Weibull shape parameter values into groups centered on integers. Correspondingly, we have hypothesized that the distribution intersections result from either competitive processes or population partitioning and the integral clustering in the shape parameter results from the occurrence of a small number of rare, rate-limiting events in disease progression. In this report we initiate a theoretical examination of these questions by exploring serial chain model dynamics and parameteric competing risks theory. The links in our chain models are composed of more than one bond, where the number of bonds in a link are denoted the link size and are the number of events necessary to break the link and, hence, the chain. We explored chains with all links of the same size or with segments of the chain composed of different size links (competition). Simulations showed that chain breakage dynamics depended on the weakest-link principle and followed kinetics of extreme-values which were very similar to human mortality kinetics. In particular, failure distributions for simple chains were Weibull-type extreme-value distributions with shape parameter values that were identifiable with the integral link size in the limit of infinite chain length. Furthermore, for chains composed of several segments of differing link size, the survival distributions for the various segments converged at a point in the S(t) tails indistinguishable from human data. This was also predicted by parameteric competing risks theory using Weibull underlying distributions. In both the competitive chain simulations and the parametric competing risks theory, however, the shape values for the intersecting distributions deviated from the integer values typical of human data. We conclude that rare events can be the source of integral shapes in human mortality, that convergence is a salient feature of multiple endpoints, but that pure competition may not be the best explanation for the exact type of convergence observable in human mortality. Finally, while the chain models were not motivated by any specific biological structures, interesting biological correlates to them may be useful in gerontological research.

Structure determination of a peptide model of the repeated helical domain in Samia cynthia ricini silk fibroin before spinning by a combination of advanced solid-state NMR methods.

PubMed

Nakazawa, Yasumoto; Asakura, Tetsuo

2003-06-18

Fibrous proteins unlike globular proteins, contain repetitive amino acid sequences, giving rise to very regular secondary protein structures. Silk fibroin from a wild silkworm, Samia cynthia ricini, consists of about 100 repeats of alternating polyalanine (poly-Ala) regions of 12-13 residues in length and Gly-rich regions. In this paper, the precise structure of the model peptide, GGAGGGYGGDGG(A)(12)GGAGDGYGAG, which is a typical repeated sequence of the silk fibroin, was determined using a combination of three kinds of solid-state NMR studies; a quantitative use of (13)C CP/MAS NMR chemical shift with conformation-dependent (13)C chemical shift contour plots, 2D spin diffusion (13)C solid-state NMR under off magic angle spinning and rotational echo double resonance. The structure of the model peptide corresponding to the silk fibroin structure before spinning was determined. The torsion angles of the central Ala residue, Ala(19), in the poly-Ala region were determined to be (phi, psi) = (-59 degrees, -48 degrees ) which are values typically associated with alpha-helical structures. However, the torsion angles of the Gly(25) residue adjacent to the C-terminal side of the poly-Ala chain were determined to be (phi, psi) = (-66 degrees, -22 degrees ) and those of Gly(12) and Ala(13) residues at the N-terminal of the poly-Ala chain to be (phi, psi) = (-70 degrees, -30 degrees ). In addition, REDOR experiments indicate that the torsion angles of the two C-terminal Ala residues, Ala(23) and Ala(24), are (phi, psi) = (-66 degrees, -22 degrees ) and those of N-terminal two Ala residues, Ala(13) and Ala(14) are (phi, psi) = (-70 degrees, -30 degrees ). Thus, the local structure of N-terminal and C-terminal residues, and also the neighboring residues of alpha-helical poly-Ala chain in the model peptide is a more strongly wound structure than found in typical alpha-helix structures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosh, Tarini Shankar; Chaitanya, S. Krishna; Sankararamakrishnan, Ramasubbu, E-mail: rsankar@iitk.ac.in

New classes of helix–helix interactions in protein structures are reported in which interactions only occur at the terminal regions or between the terminal region of one helix and the middle region of another helix. Helix–helix interactions are important for the structure, stability and function of α-helical proteins. Helices that either cross in the middle or show extensive contacts between each other, such as coiled coils, have been investigated in previous studies. Interactions between two helices can also occur only at the terminal regions or between the terminal region of one helix and the middle region of another helix. Examples ofmore » such helix pairs are found in aquaporin, H{sup +}/Cl{sup −} transporter and Bcl-2 proteins. The frequency of the occurrence of such ‘end-to-end’ (EE) and ‘end-to-middle’ (EM) helix pairs in protein structures is not known. Questions regarding the residue preferences in the interface and the mode of interhelical interactions in such helix pairs also remain unanswered. In this study, high-resolution structures of all-α proteins from the PDB have been systematically analyzed and the helix pairs that interact only in EE or EM fashion have been extracted. EE and EM helix pairs have been categorized into five classes (N–N, N–C, C–C, N–MID and C–MID) depending on the region of interaction. Nearly 13% of 5725 helix pairs belonged to one of the five classes. Analysis of single-residue propensities indicated that hydrophobic and polar residues prefer to occur in the C-terminal and N-terminal regions, respectively. Hydrophobic C-terminal interacting residues and polar N-terminal interacting residues are also highly conserved. A strong correlation exists between some of the residue properties (surface area/volume and length of side chains) and their preferences for occurring in the interface of EE and EM helix pairs. In contrast to interacting non-EE/EM helix pairs, helices in EE and EM pairs are farther apart. In these helix pairs, residues with large surface area/volume and longer side chains are preferred in the interfacial region.« less

Kinetic and Conformational Insights of Protein Adsorption onto Montmorillonite Revealed Using in Situ ATR-FTIR/2D-COS.

PubMed

Schmidt, Michael P; Martínez, Carmen Enid

2016-08-09

Protein adsorption onto clay minerals is a process with wide-ranging impacts on the environmental cycling of nutrients and contaminants. This process is influenced by kinetic and conformational factors that are often challenging to probe in situ. This study represents an in situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopic investigation of the adsorption of a model protein (bovine serum albumin (BSA)) onto a clay mineral (montmorillonite) at four concentrations (1.50, 3.75, 7.50, and 15.0 μM) under environmentally relevant conditions. At all concentrations probed, FTIR spectra show that BSA readily adsorbs onto montmorillonite. Adsorption kinetics follow an Elovich model, suggesting that primary limitations on adsorption rates are surface-related heterogeneous energetic restrictions associated with protein rearrangement and lateral protein-protein interaction. BSA adsorption onto montmorillonite fits the Langmuir model, yielding K = 5.97 × 10(5) M(-1). Deconvolution and curve fitting of the amide I band at the end of the adsorption process (∼120 min) shows a large extent of BSA unfolding upon adsorption at 1.50 μM, with extended chains and turns increasing at the expense of α-helices. At higher concentrations/surface coverages, BSA unfolding is less pronounced and a more compact structure is assumed. Two-dimensional correlation spectroscopic (2D-COS) analysis reveals three different pathways corresponding to adsorbed conformations. At 1.50 μM, adsorption increases extended chains, followed by a loss in α-helices and a subsequent increase in turns. At 3.75 μM, extended chains decrease and then aggregated strands increase and side chains decrease, followed by a decrease in turns. With 7.50 and 15.0 μM BSA, the loss of side-chain vibrations is followed by an increase in aggregated strands and a subsequent decrease in turns and extended chains. Overall, the BSA concentration and resultant surface coverage have a profound impact on the dynamics of BSA adsorption onto montmorillonite. These results enhance our understanding of the molecular-level protein dynamics and stabilization of organic matter at mineral surfaces.

Helical tomotherapy significantly reduces dose to normal tissues when compared to 3D-CRT for locally advanced rectal cancer.

PubMed

Jhaveri, Pavan M; Teh, Bin S; Paulino, Arnold C; Smiedala, Mindy J; Fahy, Bridget; Grant, Walter; McGary, John; Butler, E Brian

2009-10-01

Combined modality treatment (neoadjuvant chemoradiotherapy followed by surgery) for locally advanced rectal cancer requires special attention to various organs at risk (OAR). As a result, the use of conformal dose delivery methods has become more common in this disease setting. Helical tomotherapy is an image-guided intensity modulated delivery system that delivers dose in a fan-beam manner at 7 degree intervals around the patient and can potentially limit normal tissue from high dose radiation while adequately treating targets. In this study we dosimetrically compare helical tomotherapy to 3D-CRT for stage T3 rectal cancer. The helical tomotherapy plans were optimized in the TomoPlan system to achieve an equivalent uniform dose of 45 Gy for 10 patients with T3N0M0 disease that was at least 5cm from the anal verge. The GTV included the rectal thickening and mass evident on colonoscopy and CT scan as well as with the help of a colorectal surgeon. The CTV included the internal iliac, obturator, and pre-sacral lymphatic chains. The OAR that were outlined included the small bowel, pelvic bone marrow, femoral heads, and bladder. Anatom-e system was used to assist in delineating GTV, CTV and OAR. These 10 plans were then duplicated and optimized into 3-field 3D-CRT plans within the Pinnacle planning system.The V[45], V[40], V[30], V[20], V[10], and mean dose to the OAR were compared between the helical tomotherapy and 3D-CRT plans. Statistically significant differences were achieved in the doses to all OAR, including all volumes and means except for V[10] for the small bowel and the femoral heads. Adequate dosimetric coverage of targets were achieved with both helical tomotherapy and 3D-CRT. Helical tomotherapy reduces the volume of normal tissue receiving high-dose RT when compared to 3D-CRT treatment. Both modalities adequately dose the tumor. Clinical studies addressing the dosimetric benefits are on-going.

Development of potent anti-infective agents from Silurana tropicalis: conformational analysis of the amphipathic, alpha-helical antimicrobial peptide XT-7 and its non-haemolytic analogue [G4K]XT-7.

PubMed

Subasinghage, Anusha P; Conlon, J Michael; Hewage, Chandralal M

2010-04-01

Peptide XT-7 (GLLGP(5)LLKIA(10)AKVGS(15)NLL.NH(2)) is a cationic, leucine-rich peptide, first isolated from skin secretions of the frog, Silurana tropicalis (Pipidae). The peptide shows potent, broad-spectrum antimicrobial activity but its therapeutic potential is limited by haemolytic activity (LC(50)=140 microM). The analogue [G4K]XT-7, however, retains potent antimicrobial activity but is non-haemolytic (LC(50)>500 microM). In order to elucidate the molecular basis for this difference in properties, the three dimensional structures of XT-7 and the analogue have been investigated by proton NMR spectroscopy and molecular modelling. In aqueous solution, both peptides lack secondary structure. In a 2,2,2-trifluoroethanol (TFE-d(3))-H(2)O mixed solvent system, XT-7 is characterised by a right handed alpha-helical conformation between residues Leu(3) and Leu(17) whereas [G4K]XT-7 adopts a more restricted alpha-helical conformation between residues Leu(6) and Leu(17). A similar conformation for XT-7 in 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) micellular media was observed with a helical segment between Leu(3) and Leu(17). However, differences in side chain orientations restricting the hydrophilic residues to a smaller patch resulted in an increased hydrophobic surface relative to the conformation in TFE-H(2)O. Molecular modelling of the structures obtained in our study demonstrates the amphipathic character of the helical segments. It is proposed that the marked decrease in haemolytic activity produced by the substitution Gly(4)-->Lys in XT-7 arises from a decrease in both helicity and hydrophobicity. These studies may facilitate the development of potent but non-toxic anti-infective agents based upon the structure of XT-7. Copyright 2009 Elsevier B.V. All rights reserved.

Synthesis of triple-stranded complexes using bis(dipyrromethene) ligands.

PubMed

Zhang, Zhan; Dolphin, David

2010-12-20

The reaction of an α-free, β,β'-linked bis(dipyrromethene) ligand with Fe(3+) or Co(3+) led to noninterconvertible triple-stranded helicates and mesocates. In the present context, a stable α-free ligand 2 has been developed and complexation of ligands 1 and 2 with diamagnetic Co(3+), Ga(3+), and In(3+) has been studied. The triple-stranded M(2)1(3) (M = Ga, In) and M(2)2(3) (M = Co, Ga, In) complexes were characterized using matrix-assisted laser desorption ionization time-of-flight spectrometry, (1)H NMR and UV-vis spectroscopy, and X-ray crystallography. Again, the (1)H NMR analysis showed that both the triple-stranded helicates and mesocates were generated in this metal-directed assembly. Consistent with our previous finding on coordinatively inert Co(3+) complexes, variable-temperature NMR spectroscopy indicated that the triple-stranded helicate and mesocate of labile In(3+) did not interconvert in solution, either. However, the diastereoselectivity of the M(2)2(3) complexes was found to improve with an increase in the reaction temperature. Taken together, this study complements the coordination chemistry of poly(dipyrromethene) ligands and provides further insight into the formation of helicates versus mesocates.

O-linked oligosaccharides on insulin receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collier, E.; Gorden, P.

1991-02-01

The insulin receptor, an integral membrane glycoprotein, is synthesized as a single-chain precursor that is cleaved to produce two mature subunits, both of which contain N-linked oligosaccharide chains and covalently linked fatty acids. We report that the beta-subunit also contains O-linked oligosaccharides. The proreceptor, alpha-subunit, and beta-subunit were labeled with (3H)mannose and (3H)galactose in the presence or absence of an inhibitor of O-linked glycosylation. Tryptic peptides from each component were separated by reverse-phase high-performance liquid chromatography. N- and O-linked oligosaccharide chains were identified on these peptides by specific enzymatic digestions. The proreceptor and alpha-subunit contained only N-linked oligosaccharides, whereas themore » beta-subunit contained both N- and O-linked oligosaccharides. The O-linked oligosaccharide chains were attached to a single tryptic fraction of the beta-subunit, which also contained N-linked chains. This fraction was further localized to the NH2-terminal tryptic peptide of the beta-subunit by specific immunoprecipitation with an anti-peptide antibody with specificity for this region. Binding of insulin and autophosphorylation of the beta-subunit were not dependent on O-linked glycosylation, because cells grown in the presence of the inhibitor exhibited a normal dose response to insulin. Therefore, the insulin receptor contains O-linked oligosaccharides on the NH2-terminal tryptic peptide of the beta-subunit, and these O-linked oligosaccharides are not necessary to the binding or autophosphorylation function of the receptor.« less

Cardiomyopathy mutations in the tail of β-cardiac myosin modify the coiled-coil structure and affect integration into thick filaments in muscle sarcomeres in adult cardiomyocytes.

PubMed

Wolny, Marcin; Colegrave, Melanie; Colman, Lucy; White, Ed; Knight, Peter J; Peckham, Michelle

2013-11-01

It is unclear why mutations in the filament-forming tail of myosin heavy chain (MHC) cause hypertrophic or dilated cardiomyopathy as these mutations should not directly affect contraction. To investigate this, we first investigated the impact of five hypertrophic cardiomyopathy-causing (N1327K, E1356K, R1382W, E1555K, and R1768K) and one dilated cardiomyopathy-causing (R1500W) tail mutations on their ability to incorporate into muscle sarcomeres in vivo. We used adenoviral delivery to express full-length wild type or mutant enhanced GFP-MHC in isolated adult cardiomyocytes. Three mutations (N1327K, E1356K, and E1555K) reduced enhanced GFP-MHC incorporation into muscle sarcomeres, whereas the remainder had no effect. No mutations significantly affected contraction. Fluorescence recovery after photobleaching showed that fluorescence recovery for the mutation that incorporated least well (N1327K) was significantly faster than that of WT with half-times of 25.1 ± 1.8 and 32.2 ± 2.5 min (mean ± S.E.), respectively. Next, we determined the effects of each mutation on the helical properties of wild type and seven mutant peptides (7, 11, or 15 heptads long) from the myosin tail by circular dichroism. R1382W and E1768K slightly increased the α-helical nature of peptides. The remaining mutations reduced α-helical content, with N1327K showing the greatest reduction. Only peptides containing residues 1301-1329 were highly α-helical suggesting that this region helps in initiation of coiled coil. These results suggest that small effects of mutations on helicity translate into a reduced ability to incorporate into sarcomeres, which may elicit compensatory hypertrophy.

Constructing and decoding unconventional ubiquitin chains.

PubMed

Behrends, Christian; Harper, J Wade

2011-05-01

One of the most notable discoveries in the ubiquitin system during the past decade is the extensive use of diverse chain linkages to control signaling networks. Although the utility of Lys48- and Lys63-linked chains in protein turnover and molecular assembly, respectively, are well known, we are only beginning to understand how unconventional chain linkages are formed on target proteins and how such linkages are decoded by specific binding proteins. In this review, we summarize recent efforts to elucidate the machinery and mechanisms controlling assembly of Lys11-linked and linear (or Met1-linked) ubiquitin chains, and describe current models for how these chain types function in immune signaling and cell-cycle control.

The properties conferred upon triple-helical collagen-mimetic peptides by the presence of cysteine residues

PubMed Central

Slatter, David A.; Bihan, Dominique G.; Jarvis, Gavin E.; Stone, Rachael; Pugh, Nicholas; Giddu, Sumana; Farndale, Richard W.

2012-01-01

Recently, the ability of polymeric collagen-like peptides to regulate cell behavior has generated great interest. A triple-helical peptide known as collagen-related peptide (CRP) contains the sequence (Gly-Pro-Hyp)10. With Gly-Pro-Cys triplets appended to both of its termini, designated CRPcys, chemical cross-linking using heterobifunctional reagents generates CRPcys-XL, a potent, widely used, polymeric agonist for platelet Glycoprotein VI, whereas non-cross-linked, monomeric CRPcys antagonizes Glycoprotein VI. Here, we describe how cysteine in these triplets may also undergo random air-induced oxidation, especially upon prolonged storage or repeated freeze–thawing, to form disulphide bonds, resulting in a lesser degree of polymerization than with chemical cross-linking. We investigated the monomeric and polymeric states of these and other cysteine-containing collagen-derived peptides, using gel filtration and dynamic light scattering, allowing the size of a CRP-XL aggregate to be estimated. The effect of cysteine thiols upon peptide adsorption to surfaces and subsequent platelet responses was investigated. This demonstrated that cysteine is required for strong binding to glass coverslips and to plastic plates used in ELISA assays. PMID:22555281

The properties conferred upon triple-helical collagen-mimetic peptides by the presence of cysteine residues.

PubMed

Slatter, David A; Bihan, Dominique G; Jarvis, Gavin E; Stone, Rachael; Pugh, Nicholas; Giddu, Sumana; Farndale, Richard W

2012-07-01

Recently, the ability of polymeric collagen-like peptides to regulate cell behavior has generated great interest. A triple-helical peptide known as collagen-related peptide (CRP) contains the sequence (Gly-Pro-Hyp)(10). With Gly-Pro-Cys triplets appended to both of its termini, designated CRP(cys), chemical cross-linking using heterobifunctional reagents generates CRP(cys)-XL, a potent, widely used, polymeric agonist for platelet Glycoprotein VI, whereas non-cross-linked, monomeric CRP(cys) antagonizes Glycoprotein VI. Here, we describe how cysteine in these triplets may also undergo random air-induced oxidation, especially upon prolonged storage or repeated freeze-thawing, to form disulphide bonds, resulting in a lesser degree of polymerization than with chemical cross-linking. We investigated the monomeric and polymeric states of these and other cysteine-containing collagen-derived peptides, using gel filtration and dynamic light scattering, allowing the size of a CRP-XL aggregate to be estimated. The effect of cysteine thiols upon peptide adsorption to surfaces and subsequent platelet responses was investigated. This demonstrated that cysteine is required for strong binding to glass coverslips and to plastic plates used in ELISA assays. Copyright © 2012 Elsevier Inc. All rights reserved.

Molecular dynamics simulations of poly (ethylene oxide) hydration and conformation in solutions

NASA Astrophysics Data System (ADS)

Dahal, Udaya; Dormidontova, Elena

Polyethylene oxide (PEO) is one of the most actively used polymers, especially in biomedical applications due to its high hydrophilicity, biocompatibility and potency to inhibit protein adsorption. PEO solubility and conformation in water depends on its capability to form hydrogen bonds. Using atomistic molecular dynamics simulations we investigated the details of water packing around PEO chain and characterized the type and lifetime of hydrogen bonds in aqueous and mixed solvent solutions. The observed polymer chain conformation varies from an extended coil in pure water to collapsed globule in hexane and a helical-like conformation in pure isobutyric acid or isobutyric acid -water mixture in agreement with experimental observations. We'll discuss the implications of protic solvent arrangement and stability of hydrogen bonds on PEO chain conformation and mobility. This research is supported by NSF (DMR-1410928).

Study of ordered hadron chains with the ATLAS detector

DOE PAGES

Aaboud, M.; Aad, G.; Abbott, B.; ...

2017-11-29

The analysis of the momentum difference between charged hadrons in high-energy proton-proton collisions is performed in order to study coherent particle production. The observed correlation pattern agrees with a model of a helical QCD string fragmenting into a chain of ground-state hadrons. A threshold momentum difference in the production of adjacent pairs of charged hadrons is observed, in agreement with model predictions. The presence of low-mass hadron chains also explains the emergence of charge-combination-dependent two-particle correlations commonly attributed to Bose-Einstein interference. Here, the data sample consists of 190 μb –1 of minimum-bias events collected with proton-proton collisions at a center-of-massmore » energy √s=7 TeV in the early low-luminosity data taking with the ATLAS detector at the LHC.« less

Warfarin resistance associated with genetic polymorphism of VKORC1: linking clinical response to molecular mechanism using computational modeling.

PubMed

Lewis, Benjamin C; Nair, Pramod C; Heran, Subash S; Somogyi, Andrew A; Bowden, Jeffrey J; Doogue, Matthew P; Miners, John O

2016-01-01

The variable response to warfarin treatment often has a genetic basis. A protein homology model of human vitamin K epoxide reductase, subunit 1 (VKORC1), was generated to elucidate the mechanism of warfarin resistance observed in a patient with the Val66Met mutation. The VKORC1 homology model comprises four transmembrane (TM) helical domains and a half helical lid domain. Cys132 and Cys135, located in the N-terminal end of TM-4, are linked through a disulfide bond. Two distinct binding sites for warfarin were identified. Site-1, which binds vitamin K epoxide (KO) in a catalytically favorable orientation, shows higher affinity for S-warfarin compared with R-warfarin. Site-2, positioned in the domain occupied by the hydrophobic tail of KO, binds both warfarin enantiomers with similar affinity. Displacement of Arg37 occurs in the Val66Met mutant, blocking access of warfarin (but not KO) to Site-1, consistent with clinical observation of warfarin resistance.

Effects of hydrophobic and dipole-dipole interactions on the conformational transitions of a model polypeptide

NASA Astrophysics Data System (ADS)

Mu, Yan; Gao, Yi Qin

2007-09-01

We studied the effects of hydrophobicity and dipole-dipole interactions between the nearest-neighbor amide planes on the secondary structures of a model polypeptide by calculating the free energy differences between different peptide structures. The free energy calculations were performed with low computational costs using the accelerated Monte Carlo simulation (umbrella sampling) method, with a bias-potential method used earlier in our accelerated molecular dynamics simulations. It was found that the hydrophobic interaction enhances the stability of α helices at both low and high temperatures but stabilizes β structures only at high temperatures at which α helices are not stable. The nearest-neighbor dipole-dipole interaction stabilizes β structures under all conditions, especially in the low temperature region where α helices are the stable structures. Our results indicate clearly that the dipole-dipole interaction between the nearest neighboring amide planes plays an important role in determining the peptide structures. Current research provides a more unified and quantitative picture for understanding the effects of different forms of interactions on polypeptide structures. In addition, the present model can be extended to describe DNA/RNA, polymer, copolymer, and other chain systems.

The α-Helical Structure of Prodomains Promotes Translocation of Intrinsically Disordered Neuropeptide Hormones into the Endoplasmic Reticulum*

PubMed Central

Dirndorfer, Daniela; Seidel, Ralf P.; Nimrod, Guy; Miesbauer, Margit; Ben-Tal, Nir; Engelhard, Martin; Zimmermann, Richard; Winklhofer, Konstanze F.; Tatzelt, Jörg

2013-01-01

Different neuropeptide hormones, which are either too small to adopt a stable conformation or are predicted to be intrinsically disordered, are synthesized as larger precursors containing a prodomain in addition to an N-terminal signal peptide. We analyzed the biogenesis of three unstructured neuropeptide hormones and observed that translocation of these precursors into the lumen of the endoplasmic reticulum (ER) is critically dependent on the presence of the prodomain. The hormone domains could be deleted from the precursors without interfering with ER import and secretion, whereas constructs lacking the prodomain remained in the cytosol. Domain-swapping experiments revealed that the activity of the prodomains to promote productive ER import resides in their ability to adopt an α-helical structure. Removal of the prodomain from the precursor did not interfere with co-translational targeting of the nascent chain to the Sec61 translocon but with its subsequent productive translocation into the ER lumen. Our study reveals a novel function of prodomains to enable import of small or intrinsically disordered secretory proteins into the ER based on their ability to adopt an α-helical conformation. PMID:23532840

The α-helical structure of prodomains promotes translocation of intrinsically disordered neuropeptide hormones into the endoplasmic reticulum.

PubMed

Dirndorfer, Daniela; Seidel, Ralf P; Nimrod, Guy; Miesbauer, Margit; Ben-Tal, Nir; Engelhard, Martin; Zimmermann, Richard; Winklhofer, Konstanze F; Tatzelt, Jörg

2013-05-17

Different neuropeptide hormones, which are either too small to adopt a stable conformation or are predicted to be intrinsically disordered, are synthesized as larger precursors containing a prodomain in addition to an N-terminal signal peptide. We analyzed the biogenesis of three unstructured neuropeptide hormones and observed that translocation of these precursors into the lumen of the endoplasmic reticulum (ER) is critically dependent on the presence of the prodomain. The hormone domains could be deleted from the precursors without interfering with ER import and secretion, whereas constructs lacking the prodomain remained in the cytosol. Domain-swapping experiments revealed that the activity of the prodomains to promote productive ER import resides in their ability to adopt an α-helical structure. Removal of the prodomain from the precursor did not interfere with co-translational targeting of the nascent chain to the Sec61 translocon but with its subsequent productive translocation into the ER lumen. Our study reveals a novel function of prodomains to enable import of small or intrinsically disordered secretory proteins into the ER based on their ability to adopt an α-helical conformation.

Hybridization chain reaction-based instantaneous derivatization technology for chemiluminescence detection of specific DNA sequences.

PubMed

Wang, Xin; Lau, Choiwan; Kai, Masaaki; Lu, Jianzhong

2013-05-07

We propose here a new amplifying strategy that uses hybridization chain reaction (HCR) to detect specific sequences of DNA, where stable DNA monomers assemble on the magnetic beads only upon exposure to a target DNA. Briefly, in the HCR process, two complementary stable species of hairpins coexist in solution until the introduction of initiator reporter strands triggers a cascade of hybridization events that yield nicked double helices analogous to alternating copolymers. Moreover, a "sandwich-type" detection strategy is employed in our design. Magnetic beads, which are functionalized with capture DNA, are reacted with the target, and sandwiched with the above nicked double helices. Then, chemiluminescence (CL) detection proceeds via an instantaneous derivatization reaction between a specific CL reagent, 3,4,5-trimethoxylphenylglyoxal (TMPG), and the guanine nucleotides within the target DNA, reporter strands and DNA monomers for the generation of light. Our results clearly show that the amplification detection of specific sequences of DNA achieves a better performance (e.g. wide linear response range, low detection limit, and high specificity) as compared to the traditional sandwich type (capture/target/reporter) assays. Upon modification, the approach presented could be extended to detect other types of targets. We believe that this simple technique is promising for improving medical diagnosis and treatment.

X-ray-structure of a cytidylyl-3',5'-adenosine-proflavine complex: a self-paired parallel-chain double helical dimer with an intercalated acridine dye.

PubMed Central

Westhof, E; Sundaralingam, M

1980-01-01

The non-self-complementary dinucleoside monophosphate cytidylyl-3',5'-adenosine (CpA) forms a base-paired parallel-chain dimer with an intercalated proflavine. The dimer complex possesses a right-handed helical twist. The dimer helix has an irregular girth with a neutral adenine-adenine (A-A) pair, hydrogen-bonded through the N6 and N7 sites (C1'...C1' separation of 10.97 A), and a triply hydrogen-bonded protonated cytosine-cytosine (C-C) pair with a proton shared between the base N3 sites (Cl'...Cl' separation of 9.59 A). The torsion angles of the sugar-phosphate backbone are within their most preferred ranges and the sugar puckering sequence (5' leads to 3') is C3'-endo, C2'-endo. There is also a second proflavine molecule sandwiched between CpA dimers on the 21-axis. Both proflavines are necessarily disordered, being on dyad axis, and this suggests possible insights into the dynamics of intercalation of planar drugs. This structure shows that intercalation of planar drugs in nucleic acids may not be restricted to antiparallel complementary Watson-Crick pairing regions and provides additional mechanisms for acridine mutagenesis. PMID:6929524

Structural similarity between β(3)-peptides synthesized from β(3)-homo-amino acids and aspartic acid monomers.

PubMed

Ahmed, Sahar; Sprules, Tara; Kaur, Kamaljit

2014-07-01

Formation of stable secondary structures by oligomers that mimic natural peptides is a key asset for enhanced biological response. Here we show that oligomeric β(3)-hexapeptides synthesized from L-aspartic acid monomers (β(3)-peptides 1, 5a, and 6) or homologated β(3)-amino acids (β(3)-peptide 2), fold into similar stable 14-helical secondary structures in solution, except that the former form right-handed 14-helix and the later form left-handed 14-helix. β(3)-Peptides from L-Asp monomers contain an additional amide bond in the side chains that provides opportunities for more hydrogen bonding. However, based on the NMR solution structures, we found that β(3)-peptide from L-Asp monomers (1) and from homologated amino acids (2) form similar structures with no additional side-chain interactions. These results suggest that the β(3)-peptides derived from L-Asp are promising peptide-mimetics that can be readily synthesized using L-Asp monomers as well as the right-handed 14-helical conformation of these β(3)-peptides (such as 1 and 6) may prove beneficial in the design of mimics for right-handed α-helix of α-peptides. © 2014 Wiley Periodicals, Inc.

Optical and Photothermal Behaviors of Colloidal and Self-Assembled Magnetic-Plasmonic Nanostructures

NASA Astrophysics Data System (ADS)

Liu, Kai

This dissertation is based on numerous efforts in exploring the capabilties of numerical simulation for investigating novel optical phenomena in different colloidal plasmonic systems. The dissertation includes five chapters. Chapter 1 contains a general introduction to the fundamentals of plasmonic behaviors in colloidal clusters and bottom-up self-assembly methods for manufacturing colloidal clusters which include magnetic based and DNA-assisted pathways. Chapter 2 presents a systematic comparison of optical and thermodynamic properties of near-infrared colloidal nanoparticles, including SiO2 Au core-shell, Au nanocage and Au nanorod, and an example of the nanobubble-based photothermal therapy application. In Chapter 3, a optical phenomenon named Fano resonance is demonstrated in a colloidal heptamer design which consists of seven Fe 3O4 Au core-shell nanoparticles. The incorporation of the magnetic core enables a magnetic-assisted self-assembly process which will be discussed after the photonic analysis. In Chapter 4, the optical behaviors in a 1D magnetic-plasmonic chain are explored. A demonstration of the magnetic-based self-assembly of this 1D chain is given. Chapter 5 is focused on the study of the chiral optical responses in a helical nanoscale system which follows a 3D helical arrangement of Fe3O4 Au core-shell nanoparticles.

Correct folding of an α-helix and a β-hairpin using a polarized 2D torsional potential

PubMed Central

Gao, Ya; Li, Yongxiu; Mou, Lirong; Lin, Bingbing; Zhang, John Z. H.; Mei, Ye

2015-01-01

A new modification to the AMBER force field that incorporates the coupled two-dimensional main chain torsion energy has been evaluated for the balanced representation of secondary structures. In this modified AMBER force field (AMBER032D), the main chain torsion energy is represented by 2-dimensional Fourier expansions with parameters fitted to the potential energy surface generated by high-level quantum mechanical calculations of small peptides in solution. Molecular dynamics simulations are performed to study the folding of two model peptides adopting either α-helix or β-hairpin structures. Both peptides are successfully folded into their native structures using an AMBER032D force field with the implementation of a polarization scheme (AMBER032Dp). For comparison, simulations using a standard AMBER03 force field with and without polarization, as well as AMBER032D without polarization, fail to fold both peptides successfully. The correction to secondary structure propensity in the AMBER03 force field and the polarization effect are critical to folding Trpzip2; without these factors, a helical structure is obtained. This study strongly suggests that this new force field is capable of providing a more balanced preference for helical and extended conformations. The electrostatic polarization effect is shown to be indispensable to the growth of secondary structures. PMID:26039188

Fluorescence Determination of Tryptophan Side-Chain Accessibility and Dynamics in Triple-Helical Collagen-Like Peptides

PubMed Central

Simon-Lukasik, Kristine V.; Persikov, Anton V.; Brodsky, Barbara; Ramshaw, John A. M.; Laws, William R.; Alexander Ross, J. B.; Ludescher, Richard D.

2003-01-01

We report tryptophan fluorescence measurements of emission intensity, iodide quenching, and anisotropy that describe the environment and dynamics at X and Y sites in stable collagen-like peptides of sequence (Gly-X-Y)n. About 90% of tryptophans at both sites have similar solvent exposed fluorescence properties and a lifetime of 8.5–9 ns. Analysis of anisotropy decays using an associative model indicates that these long lifetime populations undergo rapid depolarizing motion with a 0.5 ns correlation time; however, the extent of fast motion at the Y site is considerably less than the essentially unrestricted motion at the X site. About 10% of tryptophans at both sites have a shorter (∼3 ns) lifetime indicating proximity to a protein quenching group; these minor populations are immobile on the peptide surface, depolarizing only by overall trimer rotation. Iodide quenching indicates that tryptophans at the X site are more accessible to solvent. Side chains at X sites are more solvent accessible and considerably more mobile than residues at Y sites and can more readily fluctuate among alternate intermolecular interactions in collagen fibrils. This fluorescence analysis of collagen-like peptides lays a foundation for studies on the structure, dynamics, and function of collagen and of triple-helical junctions in gelatin gels. PMID:12524302

An N-terminal glycine to cysteine mutation in the collagen COL1A1 gene produces moderately severe osteogenesis imperfecta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilcox, W.; Scott, L.; Cohn, D.

Osteogenesis imperfecta (OI) is usually due to mutations in the type I procollagen genes COL1A1 and COL1A2. Point mutations close to the N-terminus are generally milder than those near the C-terminus of the molecule (the gradient hypothesis of collagen mutations). We describe a patient with moderately severe OI due to a mutation in the N-terminal portion of the triple helical domain of the {alpha}1(I) chain. Electrophoretic analysis of collagen isolated from fibroblast cultures suggested the abnormal presence of a cysteine in the N-terminal portion of the {alpha}1(I) chain. Five overlapping DNA fragments amplified from fibroblast RNA were screened for mutationsmore » using single strand conformational polymorphism (SSCP) and heteroduplex analyses. Direct DNA sequence analysis of the single positive fragment demonstrated a G to T transversion, corresponding to a glycine to cysteine substitution at position 226 of the triple helical domain of the {alpha}1(I) chain. The mutation was confirmed by restriction enzyme analysis of amplified genomic DNA. The mutation was not present in fibroblasts from either phenotypically normal parent. Combining this mutation with other reported mutations, glycine to cysteine substitutions at positions 205, 211, 223, and 226 produce a moderately severe phenotype whereas flanking mutations at positions 175 and 382 produce a mild phenotype. This data supports a regional rather than a gradient model of the relationship between the nature and location of type I collagen mutations and OI phenotype.« less

Functional Architecture of the Cytoplasmic Entrance to the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore*

PubMed Central

El Hiani, Yassine; Linsdell, Paul

2015-01-01

As an ion channel, the cystic fibrosis transmembrane conductance regulator must form a continuous pathway for the movement of Cl− and other anions between the cytoplasm and the extracellular solution. Both the structure and the function of the membrane-spanning part of this pathway are well defined. In contrast, the structure of the pathway that connects the cytoplasm to the membrane-spanning regions is unknown, and functional roles for different parts of the protein forming this pathway have not been described. We used patch clamp recording and substituted cysteine accessibility mutagenesis to identify positively charged amino acid side chains that attract cytoplasmic Cl− ions to the inner mouth of the pore. Our results indicate that the side chains of Lys-190, Arg-248, Arg-303, Lys-370, Lys-1041, and Arg-1048, located in different intracellular loops of the protein, play important roles in the electrostatic attraction of Cl− ions. Mutation and covalent modification of these residues have charge-dependent effects on the rate of Cl− permeation, demonstrating their functional role in maximization of Cl− flux. Other nearby positively charged side chains were not involved in electrostatic interactions with Cl−. The location of these Cl−-attractive residues suggests that cytoplasmic Cl− ions enter the pore via a lateral portal located between the cytoplasmic extensions to the fourth and sixth transmembrane helices; a secondary, functionally less relevant portal might exist between the extensions to the 10th and 12th transmembrane helices. These results define the cytoplasmic mouth of the pore and show how it attracts Cl− ions from the cytoplasm. PMID:25944907

Helical Poly(5-alkyl-2,3-thiophene)s: Controlled Synthesis and Structure Characterization

DOE PAGES

Zhang, Hong-Hai; Ma, Chuanxu; Bonnesen, Peter V.; ...

2016-07-12

Whereas Poly(3-alkyl-2,5-thiophene)s (P3AT), with many potential applications, have been extensively investigated, their ortho-connected isomers, poly(5-alkyl-2,3-thiophene)s (P5AT), have never been reported because of the difficulty in their syntheses. We herein present the first synthesis of regioregular P5AT via controlled Suzuki cross-coupling polymerization with PEPPSI-IPr as catalyst, affording the polymers with tunable molecular weight, narrow polydispersity (PDI) and well-defined functional end groups at the gram scale. The helical geometry of P5AT was studied by a combination of NMR, small angle x-ray scattering (SAXS) and scanning tunneling microscopy (STM). Particularly, the single polymer chain of poly(5- 2 butyl-2,3-thiophene) (P5BT) on highly oriented pyrolyticmore » graphite (HOPG) substrates with either M or P helical conformation was directly observed by STM. The comparison of UV-vis absorption between poly(5-hexyl-2,3-thiophene) (P5HT) (λ = 345 nm) and poly(3-hexyl-2,5- thiophene) (P3HT) (λ = 450 nm) indicated that the degree of conjugation of the backbone in P5HT is less than in P3HT, which may be a consequence of the helical geometry of the former compared to the more planar geometry of the latter. Moreover, we found that P5HT can emit green fluorescence under UV (λ = 360 nm) irradiation« less

Exploring the Molecular Origins of Bio(in)compatibility: Adhesion Between Proteins and Individual Chains of Poly(ethylene oxide)

NASA Astrophysics Data System (ADS)

Rixman, Monica A.; Ortiz, Christine

2002-03-01

A critical determinant of the biocompatibility of implanted blood-contacting devices is the initial noncovalent adsorption of blood plasma proteins onto the biomaterial surface. Using high-resolution force spectroscopy, we have measured the complex intermolecular interaction forces between individual end-grafted PEO chains and a probe tip covalently bound with human serum albumin, the most abundant blood plasma protein in the human body. On approach, a long-range, nonlinear repulsive force is observed. Upon retraction, however, adhesion between the HSA probe tip and PEO chain occurs, which in many cases is strong enough to allow long-range adhesion and stretching of the individual PEO chains. The known PEO strain-induced conformational transition from the helical (ttg) to the planar (ttt) conformation is clearly observed and seen to shift to lower force values. Statistical analysis of adhesion data, comparison to a variety of control experiments, and theoretical modeling enable us to interpret these experimental results in terms of electrostatic interactions, hydrogen bonding, and steric forces.

Crystal structure of bovine Cu,Zn superoxide dismutase at 3 A resolution: chain tracing and metal ligands.

PubMed Central

Richardson, J; Thomas, K A; Rubin, B H; Richardson, D C

1975-01-01

An electron density map at 3 angstrom resolution has been calculated for Cu2+, Zn2+ superoxide dismutase from bovine erythrocytes, and the course of the main chain has been traced. The dominant structural feature is an 8-stranded barrel of antiparallel beta-pleated sheet. There is one very short helical section and two long loops of non-repetitive structure. The Cu and Zn are bound between the loops and one side of the beta barrel and are about 6 Angstrom apart, with a common histidine ligand. The Cu has four histidine ligands in a somewhat distorted square plane, and the Zn has three histidines and an aspartate in approximately tetrahedral arrangement. The two coppers of a dimer are about 34 Angstrom apart. The two subunits have essentially the same conformation and have an extensive contact area that mainly involves hydrophobic side chain interactions. The overall folding pattern of the polypeptide chain is very similar to that of an immunoglobulin domain. Images PMID:1055410

Pillared-layer microporous metal-organic frameworks constructed by robust hydrogen bonds. Synthesis, characterization, and magnetic and adsorption properties of 2,2'-biimidazole and carboxylate complexes.

PubMed

Ding, Bing-Bing; Weng, Yan-Qin; Mao, Zong-Wan; Lam, Chi-Keung; Chen, Xiao-Ming; Ye, Bao-Hui

2005-11-28

Two new isostructural complexes [M(H2biim)3][M(btc)(Hbiim)].2H2O (M = Co, (1); M = Ni, (2)) (btc = 1,3,5-benzenetricarboxylate; H2biim = 2,2'-biimidazole) have been synthesized and characterized by single-crystal X-ray diffraction. They present a unique structure consisting of two distinct units: the monomeric cations [M(H2biim)3]2+ and the two-dimensional (2D) anionic polymer [M(Hbiim)(btc)]2-. In the anionic moiety, the Hbiim- monoanion is simultaneously coordinated to one metal atom in a bidentate mode and further to another metal atom in a monodentate mode. The imidazolate groups bridge the two adjacent metal ions into a helical chain which is further arranged in left- and right-handed manners. These chains are bridged by btc ligands into a 2D brick wall structure. The most interesting aspect is that the [M(H2biim)3]2+ cations act as pillars and link the anionic layers via robust heteromeric hydrogen-bonded synthons (9) and (7) formed by the uncoordinated oxygen atoms of carboxylate groups and the H2biim ligands, resulting in a microporous metal-organic framework with one-dimensional (1D) channels (ca. 11.85 angstroms x 11.85 angstroms for 1 and 11.43 angstroms x 11.43 angstroms for 2). Magnetic properties of these two complexes have also been studied in the temperature range of 2-300 K, and their magnetic susceptibilities obey the Curie-Weiss law in the temperature range of 20-300 K (for 1) and 2-300 K (for 2), respectively, showing anti-ferromagnetic coupling through imidazolate bridging. Taking into consideration the Heisenberg infinite chain model as well as the possibility of chain-to-chain and chain-to-cation interactions, the anti-ferromagnetic exchange of 2 is analyzed via a correction for the molecular field, giving the values of g(cat) = 2.296, g(Ni) = 2.564, J = -13.30 cm(-1), and zJ' = -0.017 cm(-1). The microporous frameworks are stable at ca. 350 degrees C. They do not collapse after removal of the guest water molecules in the channels, and they adsorb methanol molecules selectively.

Trimerization and Triple Helix Stabilization of the Collagen XIX NC2 Domain*

PubMed Central

Boudko, Sergei P.; Engel, Jürgen; Bächinger, Hans Peter

2008-01-01

The mechanisms of chain selection and assembly of fibril-associated collagens with interrupted triple helices (FACITs) must differ from that of fibrillar collagens, since they lack the characteristic C-propeptide. We analyzed two carboxyl-terminal noncollagenous domains, NC2 and NC1, of collagen XIX as potential trimerization units and found that NC2 forms a stable trimer and substantially stabilizes a collagen triple helix attached to either end. In contrast, the NC1 domain requires formation of an adjacent collagen triple helix to form interchain disulfide bridges. The NC2 domain of collagen XIX and probably of other FACITs is responsible for chain selection and trimerization. PMID:18845531

Chiroptical studies on supramolecular chirality of molecular aggregates.

PubMed

Sato, Hisako; Yajima, Tomoko; Yamagishi, Akihiko

2015-10-01

The attempts of applying chiroptical spectroscopy to supramolecular chirality are reviewed with a focus on vibrational circular dichroism (VCD). Examples were taken from gels, solids, and monolayers formed by low-molecular mass weight chiral gelators. Particular attention was paid to a group of gelators with perfluoroalkyl chains. The effects of the helical conformation of the perfluoroalkyl chains on the formation of chiral architectures are reported. It is described how the conformation of a chiral gelator was determined by comparing the experimental and theoretical VCD spectra together with a model proposed for the molecular aggregation in fibrils. The results demonstrate the potential utility of the chiroptical method in analyzing organized chiral aggregates. © 2015 Wiley Periodicals, Inc.

Thermodynamic characterization of a triple-helical three-way junction containing a Hoogsteen branch point.

PubMed

Hüsler, P L; Klump, H H

1995-09-10

We have designed a Hoogsteen (HG) triple-helical three-way junction (ternary complex) constructed from three 33-mer oligonucleotides based on the same subset of sequences used for the Watson-Crick (WC) triple-helical three-way junction, characterized previously (P. L. Hüsler and H. H. Klump (1994) Arch. Biochem. Biophys., 313, 29-38). The junction differs primarily in the assembly of the branch point and the ends of the arms. The three oligonucleotides can each fold into a WC hairpin, linked by a four-member cytosine loop, each containing a homo-pyrimidine 10-mer single-strand extension. On lowering the pH (between 6 and 4), the extensions mutually associate to one of the other hairpins via Hoogsteen (HG) hydrogen bonding. Collectively, this process results in the formation of the branch point and the triple-helical arms. The HG triple-helical three-way junction is characterized by gel electrophoresis, circular dichroism, uv melting, and differential scanning calorimetry. The junction undergoes thermal unfolding in two distinct temperature regions. In the temperature range 15 to 50 degrees C loss of HG base pairing results in the dissociation of the three-way junction. Between 55 and 95 degrees C the resulting hairpins undergo further successive unfolding. The overall calorimetric unfolding enthalpy and entropy changes associated with the loss of HG base pairing are approximately equal to the sum of the enthalpy and entropy changes associated with the dissociation of the HG base pairing in the isolated arms (170.6 kcal.mol-1; 540.1 cal.mol-1.K-1). It is apparent from these results that in the proximity of the branch point the structure is not perturb or strain. This result is contrary to the results obtained for the WC triple-helical three-way and for three-way junctions constructed from canonical double-helical DNA. Complete folding of the junction requires either high Na+ (600 mM) ion concentrations or 40-60 mM Mg2+.

Continuous chain bit with downhole cycling capability

DOEpatents

Ritter, Don F.; St. Clair, Jack A.; Togami, Henry K.

1983-01-01

A continuous chain bit for hard rock drilling is capable of downhole cycling. A drill head assembly moves axially relative to a support body while the chain on the head assembly is held in position so that the bodily movement of the chain cycles the chain to present new composite links for drilling. A pair of spring fingers on opposite sides of the chain hold the chain against movement. The chain is held in tension by a spring-biased tensioning bar. A head at the working end of the chain supports the working links. The chain is centered by a reversing pawl and piston actuated by the pressure of the drilling mud. Detent pins lock the head assembly with respect to the support body and are also operated by the drilling mud pressure. A restricted nozzle with a divergent outlet sprays drilling mud into the cavity to remove debris. Indication of the centered position of the chain is provided by noting a low pressure reading indicating proper alignment of drilling mud slots on the links with the corresponding feed branches.

Topological and statistical properties of nonlinear force-free fields

NASA Astrophysics Data System (ADS)

Mangalam, A.; Prasad, A.

2018-01-01

We use our semi-analytic solution of the nonlinear force-free field equation to construct three-dimensional magnetic fields that are applicable to the solar corona and study their statistical properties for estimating the degree of braiding exhibited by these fields. We present a new formula for calculating the winding number and compare it with the formula for the crossing number. The comparison is shown for a toy model of two helices and for realistic cases of nonlinear force-free fields; conceptually the formulae are nearly the same but the resulting distributions calculated for a given topology can be different. We also calculate linkages, which are useful topological quantities that are independent measures of the contribution of magnetic braiding to the total free energy and relative helicity of the field. Finally, we derive new analytical bounds for the free energy and relative helicity for the field configurations in terms of the linking number. These bounds will be of utility in estimating the braided energy available for nano-flares or for eruptions.

Conformational Changes in the Epidermal Growth Factor Receptor: Role of the Transmembrane Domain Investigated by Coarse-Grained MetaDynamics Free Energy Calculations

PubMed Central

2016-01-01

The epidermal growth factor receptor (EGFR) is a dimeric membrane protein that regulates key aspects of cellular function. Activation of the EGFR is linked to changes in the conformation of the transmembrane (TM) domain, brought about by changes in interactions of the TM helices of the membrane lipid bilayer. Using an advanced computational approach that combines Coarse-Grained molecular dynamics and well-tempered MetaDynamics (CG-MetaD), we characterize the large-scale motions of the TM helices, simulating multiple association and dissociation events between the helices in membrane, thus leading to a free energy landscape of the dimerization process. The lowest energy state of the TM domain is a right-handed dimer structure in which the TM helices interact through the N-terminal small-X3-small sequence motif. In addition to this state, which is thought to correspond to the active form of the receptor, we have identified further low-energy states that allow us to integrate with a high level of detail a range of previous experimental observations. These conformations may lead to the active state via two possible activation pathways, which involve pivoting and rotational motions of the helices, respectively. Molecular dynamics also reveals correlation between the conformational changes of the TM domains and of the intracellular juxtamembrane domains, paving the way for a comprehensive understanding of EGFR signaling at the cell membrane. PMID:27459426

Conformational Changes in the Epidermal Growth Factor Receptor: Role of the Transmembrane Domain Investigated by Coarse-Grained MetaDynamics Free Energy Calculations.

PubMed

Lelimousin, Mickaël; Limongelli, Vittorio; Sansom, Mark S P

2016-08-24

The epidermal growth factor receptor (EGFR) is a dimeric membrane protein that regulates key aspects of cellular function. Activation of the EGFR is linked to changes in the conformation of the transmembrane (TM) domain, brought about by changes in interactions of the TM helices of the membrane lipid bilayer. Using an advanced computational approach that combines Coarse-Grained molecular dynamics and well-tempered MetaDynamics (CG-MetaD), we characterize the large-scale motions of the TM helices, simulating multiple association and dissociation events between the helices in membrane, thus leading to a free energy landscape of the dimerization process. The lowest energy state of the TM domain is a right-handed dimer structure in which the TM helices interact through the N-terminal small-X3-small sequence motif. In addition to this state, which is thought to correspond to the active form of the receptor, we have identified further low-energy states that allow us to integrate with a high level of detail a range of previous experimental observations. These conformations may lead to the active state via two possible activation pathways, which involve pivoting and rotational motions of the helices, respectively. Molecular dynamics also reveals correlation between the conformational changes of the TM domains and of the intracellular juxtamembrane domains, paving the way for a comprehensive understanding of EGFR signaling at the cell membrane.

Functional interactions between A' helices in the C-linker of open CNG channels.

PubMed

Hua, Li; Gordon, Sharona E

2005-03-01

Cyclic nucleotide-gated (CNG) channels are nonselective cation channels that are activated by the direct binding of the cyclic nucleotides cAMP and cGMP. The region linking the last membrane-spanning region (S6) to the cyclic nucleotide binding domain in the COOH terminus, termed the C-linker, has been shown to play an important role in coupling cyclic nucleotide binding to opening of the pore. In this study, we explored the intersubunit proximity between the A' helices of the C-linker regions of CNGA1 in functional channels using site-specific cysteine substitution. We found that intersubunit disulfide bonds can be formed between the A' helices in open channels, and that inducing disulfide bonds in most of the studied constructs resulted in potentiation of channel activation. This suggests that the A' helices of the C-linker regions are in close proximity when the channel is in the open state. Our finding is not compatible with a homology model of the CNGA1 C-linker made from the recently published X-ray crystallographic structure of the hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channel COOH terminus, and leads us to suggest that the C-linker region depicted in the crystal structure may represent the structure of the closed state. The opening conformational change would then involve a movement of the A' helices from a position parallel to the axis of the membrane to one perpendicular to the axis of the membrane.

Assembly and Function of Heterotypic Ubiquitin Chains in Cell-Cycle and Protein Quality Control.

PubMed

Yau, Richard G; Doerner, Kerstin; Castellanos, Erick R; Haakonsen, Diane L; Werner, Achim; Wang, Nan; Yang, X William; Martinez-Martin, Nadia; Matsumoto, Marissa L; Dixit, Vishva M; Rape, Michael

2017-11-02

Posttranslational modification with ubiquitin chains controls cell fate in all eukaryotes. Depending on the connectivity between subunits, different ubiquitin chain types trigger distinct outputs, as seen with K48- and K63-linked conjugates that drive protein degradation or complex assembly, respectively. Recent biochemical analyses also suggested roles for mixed or branched ubiquitin chains, yet without a method to monitor endogenous conjugates, the physiological significance of heterotypic polymers remained poorly understood. Here, we engineered a bispecific antibody to detect K11/K48-linked chains and identified mitotic regulators, misfolded nascent polypeptides, and pathological Huntingtin variants as their endogenous substrates. We show that K11/K48-linked chains are synthesized and processed by essential ubiquitin ligases and effectors that are mutated across neurodegenerative diseases; accordingly, these conjugates promote rapid proteasomal clearance of aggregation-prone proteins. By revealing key roles of K11/K48-linked chains in cell-cycle and quality control, we establish heterotypic ubiquitin conjugates as important carriers of biological information. Copyright © 2017 Elsevier Inc. All rights reserved.

The chain of cross-contamination: link-by-link.

PubMed

Schwartz, Jeanne

2002-01-01

Conscious efforts must be made to break the chain of cross-contamination--link-by-link. Pay attention to detail Avoid being careless Avoid touching objects while wearing soiled gloves Frequently wash hands (15-second hand washing) to remove pathogens--before and after gloving, and before handling food or drink Wear all PPE, and change accordingly.

Signaled and Unsignaled Terminal Links in Concurrent Chains I: Effects of Reinforcer Probability and Immediacy

ERIC Educational Resources Information Center

Mattson, Karla M.; Hucks, Andrew; Grace, Randolph C.; McLean, Anthony P.

2010-01-01

Eight pigeons responded in a three-component concurrent-chains procedure, with either independent or dependent initial links. Relative probability and immediacy of reinforcement in the terminal links were both varied, and outcomes on individual trials (reinforcement or nonreinforcement) were either signaled or unsignaled. Terminal-link fixed-time…

Machine learning of single molecule free energy surfaces and the impact of chemistry and environment upon structure and dynamics

NASA Astrophysics Data System (ADS)

Mansbach, Rachael A.; Ferguson, Andrew L.

2015-03-01

The conformational states explored by polymers and proteins can be controlled by environmental conditions (e.g., temperature, pressure, and solvent) and molecular chemistry (e.g., molecular weight and side chain identity). We introduce an approach employing the diffusion map nonlinear machine learning technique to recover single molecule free energy landscapes from molecular simulations, quantify changes to the landscape as a function of external conditions and molecular chemistry, and relate these changes to modifications of molecular structure and dynamics. In an application to an n-eicosane chain, we quantify the thermally accessible chain configurations as a function of temperature and solvent conditions. In an application to a family of polyglutamate-derivative homopeptides, we quantify helical stability as a function of side chain length, resolve the critical side chain length for the helix-coil transition, and expose the molecular mechanisms underpinning side chain-mediated helix stability. By quantifying single molecule responses through perturbations to the underlying free energy surface, our approach provides a quantitative bridge between experimentally controllable variables and microscopic molecular behavior, guiding and informing rational engineering of desirable molecular structure and function.

Machine learning of single molecule free energy surfaces and the impact of chemistry and environment upon structure and dynamics.

PubMed

Mansbach, Rachael A; Ferguson, Andrew L

2015-03-14

The conformational states explored by polymers and proteins can be controlled by environmental conditions (e.g., temperature, pressure, and solvent) and molecular chemistry (e.g., molecular weight and side chain identity). We introduce an approach employing the diffusion map nonlinear machine learning technique to recover single molecule free energy landscapes from molecular simulations, quantify changes to the landscape as a function of external conditions and molecular chemistry, and relate these changes to modifications of molecular structure and dynamics. In an application to an n-eicosane chain, we quantify the thermally accessible chain configurations as a function of temperature and solvent conditions. In an application to a family of polyglutamate-derivative homopeptides, we quantify helical stability as a function of side chain length, resolve the critical side chain length for the helix-coil transition, and expose the molecular mechanisms underpinning side chain-mediated helix stability. By quantifying single molecule responses through perturbations to the underlying free energy surface, our approach provides a quantitative bridge between experimentally controllable variables and microscopic molecular behavior, guiding and informing rational engineering of desirable molecular structure and function.

Lysyl Hydroxylase 2 Is Secreted by Tumor Cells and Can Modify Collagen in the Extracellular Space.

PubMed

Chen, Yulong; Guo, Houfu; Terajima, Masahiko; Banerjee, Priyam; Liu, Xin; Yu, Jiang; Momin, Amin A; Katayama, Hiroyuki; Hanash, Samir M; Burns, Alan R; Fields, Gregg B; Yamauchi, Mitsuo; Kurie, Jonathan M

2016-12-09

Lysyl hydroxylase 2 (LH2) catalyzes the hydroxylation of lysine residues in the telopeptides of fibrillar collagens, which leads to the formation of stable collagen cross-links. Recently we reported that LH2 enhances the metastatic propensity of lung cancer by increasing the amount of stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs), which generate a stiffer tumor stroma (Chen, Y., et al. (2015) J. Clin. Invest. 125, 125, 1147-1162). It is generally accepted that LH2 modifies procollagen α chains on the endoplasmic reticulum before the formation of triple helical procollagen molecules. Herein, we report that LH2 is also secreted and modifies collagen in the extracellular space. Analyses of lung cancer cell lines demonstrated that LH2 is present in the cell lysates and the conditioned media in a dimeric, active form in both compartments. LH2 co-localized with collagen fibrils in the extracellular space in human lung cancer specimens and in orthotopic lung tumors generated by injection of a LH2-expressing human lung cancer cell line into nude mice. LH2 depletion in MC3T3 osteoblastic cells impaired the formation of HLCCs, resulting in an increase in the unmodified lysine aldehyde-derived collagen cross-link (LCC), and the addition of recombinant LH2 to the media of LH2-deficient MC3T3 cells was sufficient to rescue HLCC formation in the extracellular matrix. The finding that LH2 modifies collagen in the extracellular space challenges the current view that LH2 functions solely on the endoplasmic reticulum and could also have important implications for cancer biology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Lysyl Hydroxylase 2 Is Secreted by Tumor Cells and Can Modify Collagen in the Extracellular Space*

PubMed Central

Chen, Yulong; Guo, Houfu; Terajima, Masahiko; Banerjee, Priyam; Liu, Xin; Yu, Jiang; Momin, Amin A.; Katayama, Hiroyuki; Hanash, Samir M.; Burns, Alan R.; Fields, Gregg B.; Yamauchi, Mitsuo; Kurie, Jonathan M.

2016-01-01

Lysyl hydroxylase 2 (LH2) catalyzes the hydroxylation of lysine residues in the telopeptides of fibrillar collagens, which leads to the formation of stable collagen cross-links. Recently we reported that LH2 enhances the metastatic propensity of lung cancer by increasing the amount of stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs), which generate a stiffer tumor stroma (Chen, Y., et al. (2015) J. Clin. Invest. 125, 125, 1147–1162). It is generally accepted that LH2 modifies procollagen α chains on the endoplasmic reticulum before the formation of triple helical procollagen molecules. Herein, we report that LH2 is also secreted and modifies collagen in the extracellular space. Analyses of lung cancer cell lines demonstrated that LH2 is present in the cell lysates and the conditioned media in a dimeric, active form in both compartments. LH2 co-localized with collagen fibrils in the extracellular space in human lung cancer specimens and in orthotopic lung tumors generated by injection of a LH2-expressing human lung cancer cell line into nude mice. LH2 depletion in MC3T3 osteoblastic cells impaired the formation of HLCCs, resulting in an increase in the unmodified lysine aldehyde-derived collagen cross-link (LCC), and the addition of recombinant LH2 to the media of LH2-deficient MC3T3 cells was sufficient to rescue HLCC formation in the extracellular matrix. The finding that LH2 modifies collagen in the extracellular space challenges the current view that LH2 functions solely on the endoplasmic reticulum and could also have important implications for cancer biology. PMID:27803159

Simple Physics-Based Analytical Formulas for the Potentials of Mean Force of the Interaction of Amino Acid Side Chains in Water. VII. Charged-Hydrophobic/Polar and Polar-Hydrophobic/Polar Side Chains.

PubMed

Makowski, Mariusz; Liwo, Adam; Scheraga, Harold A

2017-01-19

The physics-based potentials of side-chain-side-chain interactions corresponding to pairs composed of charged and polar, polar and polar, charged and hydrophobic, and hydrophobic and hydrophobic side chains have been determined. A total of 144 four-dimensional potentials of mean force (PMFs) of all possible pairs of molecules modeling these pairs were determined by umbrella-sampling molecular dynamics simulations in explicit water as functions of distance and orientation, and the analytical expressions were then fitted to the PMFs. Depending on the type of interacting sites, the analytical approximation to the PMF is a sum of terms corresponding to van der Waals interactions and cavity-creation involving the nonpolar sections of the side chains and van der Waals, cavity-creation, and electrostatic (charge-dipole or dipole-dipole) interaction energies and polarization energies involving the charged or polar sections of the side chains. The model used in this work reproduces all features of the interacting pairs. The UNited RESidue force field with the new side-chain-side-chain interaction potentials was preliminarily tested with the N-terminal part of the B-domain of staphylococcal protein A (PDBL 1BDD ; a three-α-helix bundle) and UPF0291 protein YnzC from Bacillus subtilis (PDB: 2HEP ; an α-helical hairpin).

47 CFR 73.3555 - Multiple ownership.

Code of Federal Regulations, 2010 CFR

2010-10-01

... vertical ownership chain and application of the relevant attribution benchmark to the resulting product, except that wherever the ownership percentage for any link in the chain exceeds 50%, it shall not be... multiplication of the ownership percentages for each link in the vertical ownership chain and application of the...

47 CFR 73.3555 - Multiple ownership.

Code of Federal Regulations, 2011 CFR

2011-10-01

... vertical ownership chain and application of the relevant attribution benchmark to the resulting product, except that wherever the ownership percentage for any link in the chain exceeds 50%, it shall not be... multiplication of the ownership percentages for each link in the vertical ownership chain and application of the...

47 CFR 73.3555 - Multiple ownership.

Code of Federal Regulations, 2014 CFR

2014-10-01

... vertical ownership chain and application of the relevant attribution benchmark to the resulting product, except that wherever the ownership percentage for any link in the chain exceeds 50%, it shall not be... multiplication of the ownership percentages for each link in the vertical ownership chain and application of the...

47 CFR 73.3555 - Multiple ownership.

Code of Federal Regulations, 2012 CFR

2012-10-01

... vertical ownership chain and application of the relevant attribution benchmark to the resulting product, except that wherever the ownership percentage for any link in the chain exceeds 50%, it shall not be... multiplication of the ownership percentages for each link in the vertical ownership chain and application of the...

47 CFR 73.3555 - Multiple ownership.

Code of Federal Regulations, 2013 CFR

2013-10-01

... vertical ownership chain and application of the relevant attribution benchmark to the resulting product, except that wherever the ownership percentage for any link in the chain exceeds 50%, it shall not be... multiplication of the ownership percentages for each link in the vertical ownership chain and application of the...

Consensus Prediction of Charged Single Alpha-Helices with CSAHserver.

PubMed

Dudola, Dániel; Tóth, Gábor; Nyitray, László; Gáspári, Zoltán

2017-01-01

Charged single alpha-helices (CSAHs) constitute a rare structural motif. CSAH is characterized by a high density of regularly alternating residues with positively and negatively charged side chains. Such segments exhibit unique structural properties; however, there are only a handful of proteins where its existence is experimentally verified. Therefore, establishing a pipeline that is capable of predicting the presence of CSAH segments with a low false positive rate is of considerable importance. Here we describe a consensus-based approach that relies on two conceptually different CSAH detection methods and a final filter based on the estimated helix-forming capabilities of the segments. This pipeline was shown to be capable of identifying previously uncharacterized CSAH segments that could be verified experimentally. The method is available as a web server at http://csahserver.itk.ppke.hu and also a downloadable standalone program suitable to scan larger sequence collections.

Origins of structure in globular proteins.

PubMed Central

Chan, H S; Dill, K A

1990-01-01

The principal forces of protein folding--hydrophobicity and conformational entropy--are nonspecific. A long-standing puzzle has, therefore, been: What forces drive the formation of the specific internal architectures in globular proteins? We find that any self-avoiding flexible polymer molecule will develop large amounts of secondary structure, helices and parallel and antiparallel sheets, as it is driven to increasing compactness by any force of attraction among the chain monomers. Thus structure formation arises from the severity of steric constraints in compact polymers. This steric principle of organization can account for why short helices are stable in globular proteins, why there are parallel and anti-parallel sheets in proteins, and why weakly unfolded proteins have some secondary structure. On this basis, it should be possible to construct copolymers, not necessarily using amino acids, that can collapse to maximum compactness in incompatible solvents and that should then have structural organization resembling that of proteins. Images PMID:2385597

Two-dimensional scanning high-energy particle diagnostic system in Large Helical Device

NASA Astrophysics Data System (ADS)

Ozaki, T.; Goncharov, P.; Sudo, S.; Shoji, M.; Kawahata, K.; Kaneko, O.; Murakami, S.

2004-10-01

A high-energy neutral particle measurement is one of the important diagnostics for ion temperature and high-energy particle confinement analysis. The neutral particle analyzer in the large helical device is capable of wide range scanning as a feature. We have obtained various data using the horizontal scan of the analyzer. Recently, in addition to the horizontal scan, a high-speed perpendicular scan became possible which enables acquisition of new information in the poloidal direction. Two stainless blocks are set on the opposite sides of the chain in order to balance the weight (700 kg) of the analyzer and reduce the load for the motor. Therefore a very high scan speed of 1°/s can be obtained. The scanning speed is 1°/s. By adding the vertical scan, the ion temperature profile and the radial variation of the signal loss associated with the resonant loss was obtained in preliminary experimental results.

Installing hydrolytic activity into a completely de novo protein framework

NASA Astrophysics Data System (ADS)

Burton, Antony J.; Thomson, Andrew R.; Dawson, William M.; Brady, R. Leo; Woolfson, Derek N.

2016-09-01

The design of enzyme-like catalysts tests our understanding of sequence-to-structure/function relationships in proteins. Here we install hydrolytic activity predictably into a completely de novo and thermostable α-helical barrel, which comprises seven helices arranged around an accessible channel. We show that the lumen of the barrel accepts 21 mutations to functional polar residues. The resulting variant, which has cysteine-histidine-glutamic acid triads on each helix, hydrolyses p-nitrophenyl acetate with catalytic efficiencies that match the most-efficient redesigned hydrolases based on natural protein scaffolds. This is the first report of a functional catalytic triad engineered into a de novo protein framework. The flexibility of our system also allows the facile incorporation of unnatural side chains to improve activity and probe the catalytic mechanism. Such a predictable and robust construction of truly de novo biocatalysts holds promise for applications in chemical and biochemical synthesis.

Crystal structure of a designed, thermostable, heterotrimeric coiled coil.

PubMed Central

Nautiyal, S.; Alber, T.

1999-01-01

Electrostatic interactions are often critical for determining the specificity of protein-protein complexes. To study the role of electrostatic interactions for assembly of helical bundles, we previously designed a thermostable, heterotrimeric coiled coil, ABC, in which charged residues were employed to drive preferential association of three distinct, 34-residue helices. To investigate the basis for heterotrimer specificity, we have used multiwavelength anomalous diffraction (MAD) analysis to determine the 1.8 A resolution crystal structure of ABC. The structure shows that ABC forms a heterotrimeric coiled coil with the intended arrangement of parallel chains. Over half of the ion pairs engineered to restrict helix associations were apparent in the experimental electron density map. As seen in other trimeric coiled coils, ABC displays acute knobs-into-holes packing and a buried anion coordinated by core polar amino acids. These interactions validate the design strategy and illustrate how packing and polar contacts determine structural uniqueness. PMID:10210186

Shifting stroke care from the hospital to the nursing home: explaining the outcomes of a Dutch case.

PubMed

van Raak, Arno; Groothuis, Siebren; van der Aa, Robert; Limburg, Martien; Vos, Leti

2010-12-01

Supply chains can contribute to better care for stroke patients and more efficiency. However, such outcomes are hampered when links in the chain are weak. The article aims to further the knowledge about the causes and possible improvements of weak links thereby using theory about rules for action and routines (action patterns). We executed a single case study of a chain of service delivery to stroke patients by a university hospital and a nursing home in the city of Maastricht, the Netherlands. Methods included document study, interviews, observations, process mapping, use of data matrices and performance of t-tests. In the case, the care delivery process in the chain was redesigned to improve the flow of patients and to reduce the length of hospital stay. Length of stay was reduced. However, transfer of patients from the hospital to the nursing home was hampered. At this weak link in the chain, the redesign clashed with the routines of hospital paramedics who did not want to work according to the redesign. The applied theory is useful to understand why a link in a supply chain is weak. Negotiations can be used to strengthen a link. © 2010 Blackwell Publishing Ltd.

Alpha-Helical Protein Domains Unify Strength and Robustness through Hierarchical Nanostructures

DTIC Science & Technology

2009-01-23

backbone atom (hydrogen donor) of peptide i + 4 in the polypeptide chain. Consequently, at each convolution , 3.5 H- bonds are found in a parallel...signaling and deformation behavior of cytoskeletal protein networks in cells (e.g. intermediate filaments vimentin and lamin as well as actin [7, 8... convolution . The Hierarchical Bell model enables one to predict the strength of different hierarchical bond arrangements as a function of the

Structural analysis of N-linked carbohydrate chains of funnel web spider (Agelenopsis aperta) venom peptide isomerase.

PubMed

Shikata, Y; Ohe, H; Mano, N; Kuwada, M; Asakawa, N

1998-06-01

The structure of the N-linked carbohydrate chains of peptide isomerase from the venom of the funnel web spider (Agelenopsis aperta) has been analyzed. Carbohydrates were released from peptide isomerase by hydrazinolysis and reductively aminated with 2-aminopyridine. The fluorescent derivatives were purified by phenol/chloroform extraction, followed by size-exclusion HPLC. The structure of the purified pyridylamino (PA-) carbohydrate chains were analyzed by a combination of two-dimensional HPLC mapping, sugar composition analysis, sequential exoglycosidase digestions, and mass spectrometry. The peptide isomerase contains six kinds of N-linked carbohydrate chains of truncated high-mannose type, with a fucose alpha 1-6 linked to the reducing N-acetylglucosamine in approximately 80% of them.

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling.

PubMed

Su, Ting; Cheng, Jingdong; Sohmen, Daniel; Hedman, Rickard; Berninghausen, Otto; von Heijne, Gunnar; Wilson, Daniel N; Beckmann, Roland

2017-05-30

Interaction between the nascent polypeptide chain and the ribosomal exit tunnel can modulate the rate of translation and induce translational arrest to regulate expression of downstream genes. The ribosomal tunnel also provides a protected environment for initial protein folding events. Here, we present a 2.9 Å cryo-electron microscopy structure of a ribosome stalled during translation of the extremely compacted VemP nascent chain. The nascent chain forms two α-helices connected by an α-turn and a loop, enabling a total of 37 amino acids to be observed within the first 50-55 Å of the exit tunnel. The structure reveals how α-helix formation directly within the peptidyltransferase center of the ribosome interferes with aminoacyl-tRNA accommodation, suggesting that during canonical translation, a major role of the exit tunnel is to prevent excessive secondary structure formation that can interfere with the peptidyltransferase activity of the ribosome.

Employer-Led Organizations and Skill Supply Chains: Linking Worker Advancement with the Skill Needs of Employers. Issue Brief.

ERIC Educational Resources Information Center

Mills, Jack; Prince, Heath

Skill supply chains apply a chain strategy to human resources to make the labor market more efficient. They link the multiple skill levels in a given labor market within a network of recruitment pathways for employers and advancement pathways for workers. Skill supply chains are based on employers' actual skill needs and on the principle that…

Some Effects of Procedural Variations on Choice Responding in Concurrent Chains

ERIC Educational Resources Information Center

Moore, J.

2009-01-01

The present research used pigeons in a three-key operant chamber and varied procedural features pertaining to both initial and terminal links of concurrent chains. The initial links randomly alternated on the side keys during a session, while the terminal links always appeared on the center key. Both equal and unequal initial-link schedules were…

Predictive Structure and Topology of Peroxisomal ATP-Binding Cassette (ABC) Transporters

PubMed Central

Andreoletti, Pierre; Raas, Quentin; Gondcaille, Catherine; Cherkaoui-Malki, Mustapha; Trompier, Doriane; Savary, Stéphane

2017-01-01

The peroxisomal ATP-binding Cassette (ABC) transporters, which are called ABCD1, ABCD2 and ABCD3, are transmembrane proteins involved in the transport of various lipids that allow their degradation inside the organelle. Defective ABCD1 leads to the accumulation of very long-chain fatty acids and is associated with a complex and severe neurodegenerative disorder called X-linked adrenoleukodystrophy (X-ALD). Although the nucleotide-binding domain is highly conserved and characterized within the ABC transporters family, solid data are missing for the transmembrane domain (TMD) of ABCD proteins. The lack of a clear consensus on the secondary and tertiary structure of the TMDs weakens any structure-function hypothesis based on the very diverse ABCD1 mutations found in X-ALD patients. Therefore, we first reinvestigated thoroughly the structure-function data available and performed refined alignments of ABCD protein sequences. Based on the 2.85  Å resolution crystal structure of the mitochondrial ABC transporter ABCB10, here we propose a structural model of peroxisomal ABCD proteins that specifies the position of the transmembrane and coupling helices, and highlight functional motifs and putative important amino acid residues. PMID:28737695

Manipulating the membrane penetration mechanism of helical polypeptides via aromatic modification for efficient gene delivery.

PubMed

Zheng, Nan; Song, Ziyuan; Yang, Jiandong; Liu, Yang; Li, Fangfang; Cheng, Jianjun; Yin, Lichen

2017-08-01

The delivery performance of non-viral gene vectors is greatly related to their intracellular kinetics. Cationic helical polypeptides with potent membrane penetration properties and gene transfection efficiencies have been recently developed by us. However, they suffer from severe drawbacks in terms of their membrane penetration mechanisms that mainly include endocytosis and pore formation. The endocytosis mechanism leads to endosomal entrapment of gene cargos, while the charge- and helicity-induced pore formation causes appreciable cytotoxicity at high concentrations. With the attempt to overcome such critical challenges, we incorporated aromatic motifs into the design of helical polypeptides to enhance their membrane activities and more importantly, to manipulate their membrane penetration mechanisms. The aromatically modified polypeptides exhibited higher cellular internalization level than the unmodified analogue by up to 2.5 folds. Such improvement is possibly because aromatic domains promoted the polypeptides to penetrate cell membranes via direct transduction, a non-endocytosis and non-pore formation mechanism. As such, gene cargos were more efficiently delivered into cells by bypassing endocytosis and subsequently avoiding endosomal entrapment, and the material toxicity associated with excessive pore formation was also reduced. The top-performing aromatic polypeptide containing naphthyl side chains at the incorporated content of 20mol% revealed notably higher transfection efficiencies than commercial reagents in melanoma cells in vitro (by 11.7 folds) and in vivo (by 9.1 folds), and thus found potential utilities toward topical gene delivery for cancer therapy. Cationic helical polypeptides, as efficient gene delivery materials, suffer from severe drawbacks in terms of their membrane penetration mechanisms. The main cell penetration mechanisms involved are endocytosis and pore formation. However, the endocytosis mechanism has the limitation of endosomal entrapment of gene cargos, while the charge- and helicity-induced pore formation causes cytotoxicity at high concentrations. To address such critical issues toward the maximization of gene delivery efficiency, we incorporated aromatic domains into helical polypeptides to promote the cell membrane penetrations via direct transduction, which is a non-endocytosis and non-pore formation mechanism. The manipulation of their membrane penetration mechanisms allows gene cargos to be more efficiently delivered by bypassing endocytosis and subsequently avoiding endosomal entrapment. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Is Congo red an amyloid-specific dye?

PubMed

Khurana, R; Uversky, V N; Nielsen, L; Fink, A L

2001-06-22

Congo red (CR) binding, monitored by characteristic yellow-green birefringence under crossed polarization has been used as a diagnostic test for the presence of amyloid in tissue sections for several decades. This assay is also widely used for the characterization of in vitro amyloid fibrils. In order to probe the structural specificity of Congo red binding to amyloid fibrils we have used an induced circular dichroism (CD) assay. Amyloid fibrils from insulin and the variable domain of Ig light chain demonstrate induced CD spectra upon binding to Congo red. Surprisingly, the native conformations of insulin and Ig light chain also induced Congo red circular dichroism, but with different spectral shapes than those from fibrils. In fact, a wide variety of native proteins exhibited induced CR circular dichroism indicating that CR bound to representative proteins from different classes of secondary structure such as alpha (citrate synthase), alpha + beta (lysozyme), beta (concavalin A), and parallel beta-helical proteins (pectate lyase). Partially folded intermediates of apomyoglobin induced different Congo red CD bands than the corresponding native conformation, however, no induced CD bands were observed with unfolded protein. Congo red was also found to induce oligomerization of native proteins, as demonstrated by covalent cross-linking and small angle x-ray scattering. Our data suggest that Congo red is sandwiched between two protein molecules causing protein oligomerization. The fact that Congo red binds to native, partially folded conformations and amyloid fibrils of several proteins shows that it must be used with caution as a diagnostic test for the presence of amyloid fibrils in vitro.

An artificial molecular machine that builds an asymmetric catalyst

NASA Astrophysics Data System (ADS)

De Bo, Guillaume; Gall, Malcolm A. Y.; Kuschel, Sonja; De Winter, Julien; Gerbaux, Pascal; Leigh, David A.

2018-05-01

Biomolecular machines perform types of complex molecular-level tasks that artificial molecular machines can aspire to. The ribosome, for example, translates information from the polymer track it traverses (messenger RNA) to the new polymer it constructs (a polypeptide)1. The sequence and number of codons read determines the sequence and number of building blocks incorporated into the biomachine-synthesized polymer. However, neither control of sequence2,3 nor the transfer of length information from one polymer to another (which to date has only been accomplished in man-made systems through template synthesis)4 is easily achieved in the synthesis of artificial macromolecules. Rotaxane-based molecular machines5-7 have been developed that successively add amino acids8-10 (including β-amino acids10) to a growing peptide chain by the action of a macrocycle moving along a mono-dispersed oligomeric track derivatized with amino-acid phenol esters. The threaded macrocycle picks up groups that block its path and links them through successive native chemical ligation reactions11 to form a peptide sequence corresponding to the order of the building blocks on the track. Here, we show that as an alternative to translating sequence information, a rotaxane molecular machine can transfer the narrow polydispersity of a leucine-ester-derivatized polystyrene chain synthesized by atom transfer radical polymerization12 to a molecular-machine-made homo-leucine oligomer. The resulting narrow-molecular-weight oligomer folds to an α-helical secondary structure13 that acts as an asymmetric catalyst for the Juliá-Colonna epoxidation14,15 of chalcones.

Independence of Terminal-Link Entry Rate and Immediacy in Concurrent Chains

ERIC Educational Resources Information Center

Berg, Mark E.; Grace, Randolph C.

2004-01-01

In Phase 1, 4 pigeons were trained on a three-component multiple concurrent-chains procedure in which components differed only in terms of relative terminal-link entry rate. The terminal links were variable-interval schedules and were varied across four conditions to produce immediacy ratios of 4:1, 1:4, 2:1, and 1:2. Relative terminal-link entry…

Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers

NASA Technical Reports Server (NTRS)

Oliver, A. E.; Deamer, D. W.

1994-01-01

Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two populations of conductive events, one in the 0.1-0.5 pA range, and one in the 1.0-5.0 pA range, whereas nearly all events caused by poly-L-alanine were in the 0.1-0.5 pA range at an applied voltage of +60 mV. The channel-like activity appeared to switch between conductive and nonconductive states, with most open-times in the range of 50-200 ms. We conclude that hydrophobic polyamino acids produce proton-conducting defects in lipid bilayers that may be used to model functional proton channels in biological membranes.

Functional Architecture of the Cytoplasmic Entrance to the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore.

PubMed

El Hiani, Yassine; Linsdell, Paul

2015-06-19

As an ion channel, the cystic fibrosis transmembrane conductance regulator must form a continuous pathway for the movement of Cl(-) and other anions between the cytoplasm and the extracellular solution. Both the structure and the function of the membrane-spanning part of this pathway are well defined. In contrast, the structure of the pathway that connects the cytoplasm to the membrane-spanning regions is unknown, and functional roles for different parts of the protein forming this pathway have not been described. We used patch clamp recording and substituted cysteine accessibility mutagenesis to identify positively charged amino acid side chains that attract cytoplasmic Cl(-) ions to the inner mouth of the pore. Our results indicate that the side chains of Lys-190, Arg-248, Arg-303, Lys-370, Lys-1041, and Arg-1048, located in different intracellular loops of the protein, play important roles in the electrostatic attraction of Cl(-) ions. Mutation and covalent modification of these residues have charge-dependent effects on the rate of Cl(-) permeation, demonstrating their functional role in maximization of Cl(-) flux. Other nearby positively charged side chains were not involved in electrostatic interactions with Cl(-). The location of these Cl(-)-attractive residues suggests that cytoplasmic Cl(-) ions enter the pore via a lateral portal located between the cytoplasmic extensions to the fourth and sixth transmembrane helices; a secondary, functionally less relevant portal might exist between the extensions to the 10th and 12th transmembrane helices. These results define the cytoplasmic mouth of the pore and show how it attracts Cl(-) ions from the cytoplasm. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A general method for the derivation of the functional forms of the effective energy terms in coarse-grained energy functions of polymers. I. Backbone potentials of coarse-grained polypeptide chains

NASA Astrophysics Data System (ADS)

Sieradzan, Adam K.; Makowski, Mariusz; Augustynowicz, Antoni; Liwo, Adam

2017-03-01

A general and systematic method for the derivation of the functional expressions for the effective energy terms in coarse-grained force fields of polymer chains is proposed. The method is based on the expansion of the potential of mean force of the system studied in the cluster-cumulant series and expanding the all-atom energy in the Taylor series in the squares of interatomic distances about the squares of the distances between coarse-grained centers, to obtain approximate analytical expressions for the cluster cumulants. The primary degrees of freedom to average about are the angles for collective rotation of the atoms contained in the coarse-grained interaction sites about the respective virtual-bond axes. The approach has been applied to the revision of the virtual-bond-angle, virtual-bond-torsional, and backbone-local-and-electrostatic correlation potentials for the UNited RESidue (UNRES) model of polypeptide chains, demonstrating the strong dependence of the torsional and correlation potentials on virtual-bond angles, not considered in the current UNRES. The theoretical considerations are illustrated with the potentials calculated from the ab initio potential-energy surface of terminally blocked alanine by numerical integration and with the statistical potentials derived from known protein structures. The revised torsional potentials correctly indicate that virtual-bond angles close to 90° result in the preference for the turn and helical structures, while large virtual-bond angles result in the preference for polyproline II and extended backbone geometry. The revised correlation potentials correctly reproduce the preference for the formation of β-sheet structures for large values of virtual-bond angles and for the formation of α-helical structures for virtual-bond angles close to 90°.

Crystal structure of delta9 stearoyl-acyl carrier protein desaturase from castor seed and its relationship to other di-iron proteins.

PubMed Central

Lindqvist, Y; Huang, W; Schneider, G; Shanklin, J

1996-01-01

The three-dimensional structure of recombinant homodimeric delta9 stearoyl-acyl carrier protein desaturase, the archetype of the soluble plant fatty acid desaturases that convert saturated to unsaturated fatty acids, has been determined by protein crystallographic methods to a resolution of 2.4 angstroms. The structure was solved by a combination of single isomorphous replacement, anomalous contribution from the iron atoms to the native diffraction data and 6-fold non-crystallographic symmetry averaging. The 363 amino acid monomer consists of a single domain of 11 alpha-helices. Nine of these form an antiparallel helix bundle. The enzyme subunit contains a di-iron centre, with ligands from four of the alpha-helices in the helix bundle. The iron ions are bound in a highly symmetric environment, with one of the irons forming interactions with the side chains of E196 and H232 and the second iron with the side chains of E105 and H146. Two additional glutamic acid side chains, from E143 and E229, are within coordination distance to both iron ions. A water molecule is found within the second coordination sphere from the iron atoms. The lack of electron density corresponding to a mu-oxo bridge, and the long (4.2 angstroms) distance between the iron ions suggests that this probably represents the diferrous form of the enzyme. A deep channel which probably binds the fatty acid extends from the surface into the interior of the enzyme. Modelling of the substrate, stearic acid, into this channel places the delta9 carbon atom in the vicinity of one of the iron ions. Images PMID:8861937

Crystal structure of delta9 stearoyl-acyl carrier protein desaturase from castor seed and its relationship to other di-iron proteins.

PubMed

Lindqvist, Y; Huang, W; Schneider, G; Shanklin, J

1996-08-15

The three-dimensional structure of recombinant homodimeric delta9 stearoyl-acyl carrier protein desaturase, the archetype of the soluble plant fatty acid desaturases that convert saturated to unsaturated fatty acids, has been determined by protein crystallographic methods to a resolution of 2.4 angstroms. The structure was solved by a combination of single isomorphous replacement, anomalous contribution from the iron atoms to the native diffraction data and 6-fold non-crystallographic symmetry averaging. The 363 amino acid monomer consists of a single domain of 11 alpha-helices. Nine of these form an antiparallel helix bundle. The enzyme subunit contains a di-iron centre, with ligands from four of the alpha-helices in the helix bundle. The iron ions are bound in a highly symmetric environment, with one of the irons forming interactions with the side chains of E196 and H232 and the second iron with the side chains of E105 and H146. Two additional glutamic acid side chains, from E143 and E229, are within coordination distance to both iron ions. A water molecule is found within the second coordination sphere from the iron atoms. The lack of electron density corresponding to a mu-oxo bridge, and the long (4.2 angstroms) distance between the iron ions suggests that this probably represents the diferrous form of the enzyme. A deep channel which probably binds the fatty acid extends from the surface into the interior of the enzyme. Modelling of the substrate, stearic acid, into this channel places the delta9 carbon atom in the vicinity of one of the iron ions.

Structural Analysis of a β-Helical Protein Motif Stabilized by Targeted Replacements with Conformationally Constrained Amino Acids

PubMed Central

Ballano, Gema; Zanuy, David; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos

2009-01-01

Here we study conformational stabilization induced in a β-helical nanostructure by position-specific mutations. The nanostructure is constructed through the self-assembly of the β-helical building block excised from E. coli galactoside acetyltransferase (PDB code 1krr, chain A; residues 131-165). The mutations involve substitutions by cyclic, conformationally constrained amino acids. Specifically, a complete structural analysis of the Pro-Xaa-Val sequence [with Xaa being Gly, Ac3c (1-aminocyclopropane-1-carboxylic acid) and Ac5c (1-aminocyclopentane-1-carboxylic acid)], corresponding to the 148-150 loop region in the wild-type (Gly) and mutated (Ac3c and Ac5c) 1krr, has been performed using Molecular Dynamics simulations and X-ray crystallography. Simulations have been performed for the wild-type and mutants of three different systems, namely the building block, the nanoconstruct and the isolated Pro-Xaa-Val tripeptide. Furthermore, the crystalline structures of five peptides of Pro-Xaa-Val or Xaa-Val sequences have been solved by X-ray diffraction analysis and compared with theoretical predictions. Both the theoretical and crystallographic studies indicate that the Pro-Acnc-Val sequences exhibit a high propensity to adopt turn-like conformations, and this propensity is little affected by the chemical environment. Overall, the results indicate that replacement of Gly149 by Ac3c or Ac5c significantly reduce the conformational flexibility of the target site enhancing the structural specificity of the building block and the nanoconstruct derived from the 1krr β-helical motif. PMID:18811190

Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function.

PubMed

Alamo, Lorenzo; Koubassova, Natalia; Pinto, Antonio; Gillilan, Richard; Tsaturyan, Andrey; Padrón, Raúl

2017-10-01

The tarantula skeletal muscle X-ray diffraction pattern suggested that the myosin heads were helically arranged on the thick filaments. Electron microscopy (EM) of negatively stained relaxed tarantula thick filaments revealed four helices of heads allowing a helical 3D reconstruction. Due to its low resolution (5.0 nm), the unambiguous interpretation of densities of both heads was not possible. A resolution increase up to 2.5 nm, achieved by cryo-EM of frozen-hydrated relaxed thick filaments and an iterative helical real space reconstruction, allowed the resolving of both heads. The two heads, "free" and "blocked", formed an asymmetric structure named the "interacting-heads motif" (IHM) which explained relaxation by self-inhibition of both heads ATPases. This finding made tarantula an exemplar system for thick filament structure and function studies. Heads were shown to be released and disordered by Ca 2+ -activation through myosin regulatory light chain phosphorylation, leading to EM, small angle X-ray diffraction and scattering, and spectroscopic and biochemical studies of the IHM structure and function. The results from these studies have consequent implications for understanding and explaining myosin super-relaxed state and thick filament activation and regulation. A cooperative phosphorylation mechanism for activation in tarantula skeletal muscle, involving swaying constitutively Ser35 mono-phosphorylated free heads, explains super-relaxation, force potentiation and post-tetanic potentiation through Ser45 mono-phosphorylated blocked heads. Based on this mechanism, we propose a swaying-swinging, tilting crossbridge-sliding filament for tarantula muscle contraction.

Kinetic chain contributions to elbow function and dysfunction in sports.

PubMed

Ben Kibler, W; Sciascia, Aaron

2004-10-01

The elbow functions in throwing and other athletic activities as a link in the kinetic chain of force development, regulation, and transfer. Efficient function, with maximal performance and minimal injury risk, requires optimum activation of all the link in the kinetic chain. Injury is often associated with alterations in force production or regulation capabilities in links that may be distant to the site of injury. Evaluation of injured athletes should include screening examinations for these areas, and treatment and conditioning should also include these areas.

Asynchronous Movements Prior to Pore Opening in NMDA Receptors

PubMed Central

Kazi, Rashek; Gan, Quan; Talukder, Iehab; Markowitz, Michael; Salussolia, Catherine L.

2013-01-01

Glutamate-gated ion channels embedded within the neuronal membrane are the primary mediators of fast excitatory synaptic transmission in the CNS. The ion channel of these glutamate receptors contains a pore-lining transmembrane M3 helix surrounded by peripheral M1 and M4 helices. In the NMDA receptor subtype, opening of the ion channel pore, mediated by displacement of the M3 helices away from the central pore axis, occurs in a highly concerted fashion, but the associated temporal movements of the peripheral helices are unknown. To address the gating dynamics of the peripheral helices, we constrained the relative movements of the linkers that connect these helices to the ligand-binding domain using engineered cross-links, either within (intra-GluN1 or GluN2A) or between subunits. Constraining the peripheral linkers in any manner dramatically curtailed channel opening, highlighting the requirement for rearrangements of these peripheral structural elements for efficient gating to occur. However, the magnitude of this gating effect depended on the specific subunit being constrained, with the most dramatic effects occurring when the constraint was between subunits. Based on kinetic and thermodynamic analysis, our results suggest an asynchrony in the displacement of the peripheral linkers during the conformational and energetic changes leading to pore opening. Initially there are large-scale rearrangements occurring between the four subunits. Subsequently, rearrangements occur within individual subunits, mainly GluN2A, leading up to or in concert with pore opening. Thus, the conformational changes induced by agonist binding in NMDA receptors converge asynchronously to permit pore opening. PMID:23864691

Topological switching between an alpha-beta parallel protein and a remarkably helical molten globule.

PubMed

Nabuurs, Sanne M; Westphal, Adrie H; aan den Toorn, Marije; Lindhoud, Simon; van Mierlo, Carlo P M

2009-06-17

Partially folded protein species transiently exist during folding of most proteins. Often these species are molten globules, which may be on- or off-pathway to native protein. Molten globules have a substantial amount of secondary structure but lack virtually all the tertiary side-chain packing characteristic of natively folded proteins. These ensembles of interconverting conformers are prone to aggregation and potentially play a role in numerous devastating pathologies, and thus attract considerable attention. The molten globule that is observed during folding of apoflavodoxin from Azotobacter vinelandii is off-pathway, as it has to unfold before native protein can be formed. Here we report that this species can be trapped under nativelike conditions by substituting amino acid residue F44 by Y44, allowing spectroscopic characterization of its conformation. Whereas native apoflavodoxin contains a parallel beta-sheet surrounded by alpha-helices (i.e., the flavodoxin-like or alpha-beta parallel topology), it is shown that the molten globule has a totally different topology: it is helical and contains no beta-sheet. The presence of this remarkably nonnative species shows that single polypeptide sequences can code for distinct folds that swap upon changing conditions. Topological switching between unrelated protein structures is likely a general phenomenon in the protein structure universe.

Fabrication of chiroptically switchable films via co-gelation of a small chiral gelator with an achiral azobenzene-containing polymer.

PubMed

Yang, Dong; Zhang, Li; Yin, Lu; Zhao, Yin; Zhang, Wei; Liu, Minghua

2017-09-20

Helical polymers are widely found in nature and synthetic functional materials. Although a number of elaborate strategies have been developed to endow polymers with helicity through either covalent bonds or supramolecular techniques, it still remains a challenge to get the desired helical polymers with controlled handedness in an easy but effective manner. In this study, we report an easily accessible gelation-guided self-assembly system where the chirality of a gelator can be easily transferred to an achiral azobenzene-containing polymer during gelation. It is found that during the process of chiral induction, the induced chirality of the polymer was entirely dominated by the molecular chirality of the gelator. Experimentally, achiral azobenzene-containing polymers with different side-chain lengths were doped into a supramolecular gel system formed with amphiphilic N,N'-bis-(octadecyl)-l(d)-Boc-glutamic (LBG-18 or DBG-18 for short). CD spectra and SEM observation confirmed that the co-assembly of polymer/LBG-18 or polymer/DBG-18 in the xerogel state exhibited supramolecular chirality. More importantly, alternate UV and visible light irradiation on the xerogel film caused the induced CD signal to switch between on and off states. Thus a chiroptical switch was fabricated based on the isomerization of the azo-polymer in xerogel films.

Molecular self-assembly in substituted alanine derivatives: XRD, Hirshfeld surfaces and DFT studies

NASA Astrophysics Data System (ADS)

Rajalakshmi, Periasamy; Srinivasan, Navaneethakrishnan; Sivaraman, Gandhi; Razak, Ibrahim Abdul; Rosli, Mohd Mustaqim; Krishnakumar, Rajaputi Venkatraman

2014-06-01

The molecular assemblage in the crystal structures of three modified chiral amino acids, two of which are isomeric D- and L-pairs boc-L-benzothienylalanine (BLA), boc-D-benzothienylalanine (BDA) and the other boc-D-naphthylalanine (NDA) differing from this pair very slightly in the chemical modification introduced, is accurately described. The aggregation of amino acid molecules is similar in all the crystals and may be described as a twisted double helical ladder in which two complementary long helical chains formed through O-H⋯O hydrogen bonds are interconnected through the characteristic head-to-tail N-H⋯O hydrogen bonds. Thus the molecular aggregation enabled through classical hydrogen bonds may be regarded as a mimic of the characteristic double helical structure of DNA. Also, precise structural information involving these amino acid molecules with lower symmetry exhibiting higher trigonal symmetry in their self-assembly is expected to throw light on the nature and strength of intermolecular interactions and their role in self-assembly of molecular aggregates, which are crucial in developing new or at least supplement existing crystal engineering strategies. Single crystal X-ray analysis and their electronic structures were calculated at the DFT level with a detailed analysis of Hirshfeld surfaces and fingerprint plots facilitating a comparison of intermolecular interactions in building different supramolecular architectures.

Observation of Intermolecular Hydrogen Bonding Interactions in Biosynthesized and Biodegradable Poly [(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] in Chloroform and 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP).

PubMed

Sobieski, Brian J; Noda, Isao; Rabolt, John F; Chase, D Bruce

2017-10-01

In this work, we describe polymer-solvent interactions in biosynthesized and biodegradable poly[(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] (PHBHx) and the atactic homopolymer, poly(3-hydroxybutyrate) (a-PHB), which were studied both as neat polymers and in solutions of chloroform and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). Specifically, infrared frequency shifts of the carbonyl band were observed in semi-crystalline PHBHx, but not in a-PHB, because it cannot form the helical conformation required for crystallization. The carbonyl band of PHBHx exhibited the high frequency associated with amorphous structure in chloroform and the lower frequency traditionally attributed to the helical crystalline structure in HFIP. The same results were obtained for a-PHB, demonstrating that the helical structure is not required for a lower frequency carbonyl-stretching mode. It is proposed that the band shift is due to hydrogen bonding between the carbonyl and hydroxyl hydrogen in HFIP. Therefore, the carbonyl frequency observed upon crystallization is most likely due to hydrogen bonding between the carbonyl and methyl hydrogen of the neighboring polymer chain in the crystal lattice as previously suggested.

Mechanistic Studies on the Triggered Release of Liposomal Contents by Matrix Metalloproteinase-9

PubMed Central

Elegbede, Adekunle I.; Banerjee, Jayati; Hanson, Andrea J.; Tobwala, Shakila; Ganguli, Bratati; Wang, Rongying; Lu, Xiaoning; Srivastava, D. K.; Mallik, Sanku

2009-01-01

Matrix metalloproteinases (MMPs) are a class of extracellular matrix degrading enzymes over-expressed in many cancers and contribute to the metastatic ability of the cancer cells. We have recently demonstrated that liposomal contents can be released when triggered by the enzyme MMP-9. Herein, we report our results on the mechanistic studies of the MMP-9 triggered release of the liposomal contents. We synthesized peptides containing the cleavage site for MMP-9 and conjugated them with fatty acids to prepare the corresponding lipopeptides. By employing Circular Dichroism spectroscopy, we demonstrate that the lipopeptides, when incorporated in liposomes, are de-mixed in the lipid bilayers and generate triple helical structures. MMP-9 cleaves the triple helical peptides, leading to the release of the liposomal contents. Other MMPs, which cannot hydrolyze triple helical peptides, failed to release the contents from the liposomes. We also observed that the rate and the extent of release of the liposomal contents depend on the mismatch between acyl chains of the synthesized lipopeptide and phospholipid components of the liposomes. Circular Dichroism spectroscopic studies imply that the observed differences in the release reflect the ability of the liposomal membrane to anneal the defects following the enzymatic cleavage of the liposome-incorporated lipopeptides. PMID:18642903

Molecular mechanism of melting of a helical polymer crystal: Role of conformational order, packing and mobility of polymers

NASA Astrophysics Data System (ADS)

Cheerla, Ramesh; Krishnan, Marimuthu

2018-03-01

The molecular mechanism of melting of a superheated helical polymer crystal has been investigated using isothermal-isobaric molecular dynamics simulation that allows anisotropic deformation of the crystal lattice. A detailed microscopic analysis of the onset and progression of melting and accompanying changes in the polymer conformational order, translational, and orientation order of the solid along the melting pathway is presented. Upon gradual heating from room temperature to beyond the melting point at ambient pressure, the crystal exhibits signatures of premelting well below the solid-to-liquid melting transition at the melting point. The melting transition is manifested by abrupt changes in the crystal volume, lattice energy, polymer conformation, and dynamical properties. In the premelting stage, the crystal lattice structure and backbone orientation of the polymer chains are retained but with the onset of weakening of long-range helical order and interchain packing of polymers perpendicular to the fibre axis of the crystal. The premelting also marks the onset of conformational defects and anisotropic solid-state diffusion of polymers along the fibre axis. The present study underscores the importance of the interplay between intermolecular packing, interactions, and conformational dynamics at the atomic level in determining the macroscopic melting behavior of polymer crystals.

Prediction of protein secondary structure content for the twilight zone sequences.

PubMed

Homaeian, Leila; Kurgan, Lukasz A; Ruan, Jishou; Cios, Krzysztof J; Chen, Ke

2007-11-15

Secondary protein structure carries information about local structural arrangements, which include three major conformations: alpha-helices, beta-strands, and coils. Significant majority of successful methods for prediction of the secondary structure is based on multiple sequence alignment. However, multiple alignment fails to provide accurate results when a sequence comes from the twilight zone, that is, it is characterized by low (<30%) homology. To this end, we propose a novel method for prediction of secondary structure content through comprehensive sequence representation, called PSSC-core. The method uses a multiple linear regression model and introduces a comprehensive feature-based sequence representation to predict amount of helices and strands for sequences from the twilight zone. The PSSC-core method was tested and compared with two other state-of-the-art prediction methods on a set of 2187 twilight zone sequences. The results indicate that our method provides better predictions for both helix and strand content. The PSSC-core is shown to provide statistically significantly better results when compared with the competing methods, reducing the prediction error by 5-7% for helix and 7-9% for strand content predictions. The proposed feature-based sequence representation uses a comprehensive set of physicochemical properties that are custom-designed for each of the helix and strand content predictions. It includes composition and composition moment vectors, frequency of tetra-peptides associated with helical and strand conformations, various property-based groups like exchange groups, chemical groups of the side chains and hydrophobic group, auto-correlations based on hydrophobicity, side-chain masses, hydropathy, and conformational patterns for beta-sheets. The PSSC-core method provides an alternative for predicting the secondary structure content that can be used to validate and constrain results of other structure prediction methods. At the same time, it also provides useful insight into design of successful protein sequence representations that can be used in developing new methods related to prediction of different aspects of the secondary protein structure. (c) 2007 Wiley-Liss, Inc.

Probing the Interaction of Brain Fatty Acid Binding Protein (B-FABP) with Model Membranes

PubMed Central

Dyszy, Fábio; Pinto, Andressa P. A.; Araújo, Ana P. U.; Costa-Filho, Antonio J.

2013-01-01

Brain fatty acid-binding protein (B-FABP) interacts with biological membranes and delivers polyunsaturated fatty acids (FAs) via a collisional mechanism. The binding of FAs in the protein and the interaction with membranes involve a motif called “portal region”, formed by two small α-helices, A1 and A2, connected by a loop. We used a combination of site-directed mutagenesis and electron spin resonance to probe the changes in the protein and in the membrane model induced by their interaction. Spin labeled B-FABP mutants and lipidic spin probes incorporated into a membrane model confirmed that B-FABP interacts with micelles through the portal region and led to structural changes in the protein as well in the micelles. These changes were greater in the presence of LPG when compared to the LPC models. ESR spectra of B-FABP labeled mutants showed the presence of two groups of residues that responded to the presence of micelles in opposite ways. In the presence of lysophospholipids, group I of residues, whose side chains point outwards from the contact region between the helices, had their mobility decreased in an environment of lower polarity when compared to the same residues in solution. The second group, composed by residues with side chains situated at the interface between the α-helices, experienced an increase in mobility in the presence of the model membranes. These modifications in the ESR spectra of B-FABP mutants are compatible with a less ordered structure of the portal region inner residues (group II) that is likely to facilitate the delivery of FAs to target membranes. On the other hand, residues in group I and micelle components have their mobilities decreased probably as a result of the formation of a collisional complex. Our results bring new insights for the understanding of the gating and delivery mechanisms of FABPs. PMID:23555925

Aluminum Cluster-Based Materials for Propulsion and Other Applications and Catalysis

DTIC Science & Technology

2012-04-04

CuMg8- and AuMg8- . It was shown that aromaticity, traditionally used to understand stability of organic systems , can also stabilize metallic...the helical chains of arsenic and K atoms. Extensions of these to other systems is currently under study. Since 2009, 12 group publications (GP... systems that are cyclic, planar and contain (4n+2) π electrons. Only recently has this concept been extended to all-metal systems , with the seminal

Comparative Study of the Mechanical Unfolding Pathways of α- and β-Peptides.

PubMed

Uribe, Lalita; Gauss, Jürgen; Diezemann, Gregor

2015-07-02

Using molecular simulations, we analyze the unfolding pathways of various peptides. We compare the mechanical unfolding of a β-alanine's octamer (β-HAla8) and an α-alanine's decamer (α-Ala10). Using force-probe molecular-dynamics simulations, to induce unfolding, we show that the 3(14)-helix formed by β-HAla8 is mechanically more stable than the α-helix formed by α-Ala10, although both structures are stabilized by six hydrogen bonds. Additionally, computations of the potential of mean force validate this result and show that also the thermal stability of the 3(14)-helix is higher. It is demonstrated that β-HAla8 unfolds in a two-step fashion with a stable intermediate. This is contrasted with the known single-step scenario of the unfolding of α-Ala10. Furthermore, we present a study of the chain-length dependence of the mechanical unfolding pathway of the 3(14)-helix. The calculation of the dynamic strength for oligomers with chain lengths ranging from 6 to 18 monomers shows that the unfolding pathway of helices with an integer and noninteger number of turns has m + 1 and m energy barriers, respectively, with m being the number of complete turns. The additional barrier for helices with an integer number of turns is shown to be related to the breaking of the N-terminus' hydrogen bond.

Protein structure and the sequential structure of mRNA: alpha-helix and beta-sheet signals at the nucleotide level.

PubMed

Brunak, S; Engelbrecht, J

1996-06-01

A direct comparison of experimentally determined protein structures and their corresponding protein coding mRNA sequences has been performed. We examine whether real world data support the hypothesis that clusters of rare codons correlate with the location of structural units in the resulting protein. The degeneracy of the genetic code allows for a biased selection of codons which may control the translational rate of the ribosome, and may thus in vivo have a catalyzing effect on the folding of the polypeptide chain. A complete search for GenBank nucleotide sequences coding for structural entries in the Brookhaven Protein Data Bank produced 719 protein chains with matching mRNA sequence, amino acid sequence, and secondary structure assignment. By neural network analysis, we found strong signals in mRNA sequence regions surrounding helices and sheets. These signals do not originate from the clustering of rare codons, but from the similarity of codons coding for very abundant amino acid residues at the N- and C-termini of helices and sheets. No correlation between the positioning of rare codons and the location of structural units was found. The mRNA signals were also compared with conserved nucleotide features of 16S-like ribosomal RNA sequences and related to mechanisms for maintaining the correct reading frame by the ribosome.

The N-Linked Outer Chain Mannans and the Dfg5p and Dcw1p Endo-α-1,6-Mannanases Are Needed for Incorporation of Candida albicans Glycoproteins into the Cell Wall

PubMed Central

Ao, Jie; Chinnici, Jennifer L.; Maddi, Abhiram

2015-01-01

A biochemical pathway for the incorporation of cell wall protein into the cell wall of Neurospora crassa was recently proposed. In this pathway, the DFG-5 and DCW-1 endo-α-1,6-mannanases function to covalently cross-link cell wall protein-associated N-linked galactomannans, which are structurally related to the yeast outer chain mannans, into the cell wall glucan-chitin matrix. In this report, we demonstrate that the mannosyltransferase enzyme Och1p, which is needed for the synthesis of the N-linked outer chain mannan, is essential for the incorporation of cell wall glycoproteins into the Candida albicans cell wall. Using endoglycosidases, we show that C. albicans cell wall proteins are cross-linked into the cell wall via their N-linked outer chain mannans. We further demonstrate that the Dfg5p and Dcw1p α-1,6-mannanases are needed for the incorporation of cell wall glycoproteins into the C. albicans cell wall. Our results support the hypothesis that the Dfg5p and Dcw1p α-1,6-mannanases incorporate cell wall glycoproteins into the C. albicans cell wall by cross-linking outer chain mannans into the cell wall glucan-chitin matrix. PMID:26048011

Central catalytic domain of BRAP (RNF52) recognizes the types of ubiquitin chains and utilizes oligo-ubiquitin for ubiquitylation

PubMed Central

Hanada, Kazuharu; Ohsawa, Noboru

2017-01-01

Really interesting new gene (RING)-finger protein 52 (RNF52), an E3 ubiquitin ligase, is found in eukaryotes from yeast to humans. Human RNF52 is known as breast cancer type 1 susceptibility protein (BRCA1)-associated protein 2 (BRAP or BRAP2). The central catalytic domain of BRAP comprises four subdomains: nucleotide-binding α/β plait (NBP), really interesting new gene (RING) zinc finger, ubiquitin-specific protease (UBP)-like zinc finger (ZfUBP), and coiled-coil (CC). This domain architecture is conserved in RNF52 orthologs; however, the domain's function in the ubiquitin system has not been delineated. In the present study, we discovered that the RNF52 domain, comprising NBP–RING–ZfUBP–CC, binds to ubiquitin chains (oligo-ubiquitin) but not to the ubiquitin monomers, and can utilize various ubiquitin chains for ubiquitylation and auto-ubiquitylation. The RNF52 domain preferentially bound to M1- and K63-linked di-ubiquitin chains, weakly to K27-linked chains, but not to K6-, K11-, or K48-linked chains. The binding preferences of the RNF52 domain for ubiquitin-linkage types corresponded to ubiquitin usage in the ubiquitylation reaction, except for K11-, K29-, and K33-linked chains. Additionally, the RNF52 domain directly ligated the intact M1-linked, tri-, and tetra-ubiquitin chains and recognized the structural alterations caused by the phosphomimetic mutation of these ubiquitin chains. Full-length BRAP had nearly the same specificity for the ubiquitin-chain types as the RNF52 domain alone. Mass spectrometry analysis of oligomeric ubiquitylation products, mediated by the RNF52 domain, revealed that the ubiquitin-linkage types and auto-ubiquitylation sites depend on the length of ubiquitin chains. Here, we propose a model for the oligomeric ubiquitylation process, controlled by the RNF52 domain, which is not a sequential assembly process involving monomers. PMID:28768733

Induced cholesteric systems based on some cyano derivatives as host phases

NASA Astrophysics Data System (ADS)

Shkolnikova, Natalya I.; Kutulya, Lidiya A.; Vashchenko, V. V.; Fedoryako, A. P.; Lapanik, V. I.; Posledovich, N. R.

2002-12-01

Macroscopical properties of some induced cholesteric compositions based on 4-pentyl-4'-cyano derivatives of biphenyl and phenylcyclohexane as host phases have been investigated. The series of N-arylidene derivatives of (S)-1-phenylethylamine with varied both rigid moiety of the N-arylidene fragment and terminal substituent was used as chiral dopants. The influence of the chiral dopant molecular structure as well as of physical properties of the host phases used on the helical twisting power, the temperature dependence of the induced helical pitch and the N* mesophase thermal stability has been characterized. It has been concluded that the distinctions in properties of the LC systems containing the OCH2 and COO linking groups are caused by their different conformational states.

A Simpler Nucleic Acid

NASA Technical Reports Server (NTRS)

Orgel, Leslie

2000-01-01

It has been supposed that for a nucleic acid analog to pair with RNA it must, like RNA, have a backbone with at least a sixatom repeat; a shorter backbone presumably would not stretch far enough to bind RNA properly. The Eschenmoser group has shown, however, that this first impression is incorrect.As they report in their new paper, Eschenmoser and co-workers ( I ) have now synthesized a substantial number of these polymers, which are called (L)-a-threofuranosyl oligonucleotides or TNAs. They are composed of bases linked to a threose sugar-phosphate backbone, with phosphodiester bonds connecting the nucleotides. The investigators discovered that pairs of complementary TNAs do indeed form stable Watson-Crick double helices and, perhaps more importantly, that TNAs form stable double helices with complementary RNAs and DNAs.

The signaling helix: a common functional theme in diverse signaling proteins

PubMed Central

Anantharaman, Vivek; Balaji, S; Aravind, L

2006-01-01

Background The mechanism by which the signals are transmitted between receptor and effector domains in multi-domain signaling proteins is poorly understood. Results Using sensitive sequence analysis methods we identify a conserved helical segment of around 40 residues in a wide range of signaling proteins, including numerous sensor histidine kinases such as Sln1p, and receptor guanylyl cyclases such as the atrial natriuretic peptide receptor and nitric oxide receptors. We term this helical segment the signaling (S)-helix and present evidence that it forms a novel parallel coiled-coil element, distinct from previously known helical segments in signaling proteins, such as the Dimerization-Histidine phosphotransfer module of histidine kinases, the intra-cellular domains of the chemotaxis receptors, inter-GAF domain helical linkers and the α-helical HAMP module. Analysis of domain architectures allowed us to reconstruct the domain-neighborhood graph for the S-helix, which showed that the S-helix almost always occurs between two signaling domains. Several striking patterns in the domain neighborhood of the S-helix also became evident from the graph. It most often separates diverse N-terminal sensory domains from various C-terminal catalytic signaling domains such as histidine kinases, cNMP cyclase, PP2C phosphatases, NtrC-like AAA+ ATPases and diguanylate cyclases. It might also occur between two sensory domains such as PAS domains and occasionally between a DNA-binding HTH domain and a sensory domain. The sequence conservation pattern of the S-helix revealed the presence of a unique constellation of polar residues in the dimer-interface positions within the central heptad of the coiled-coil formed by the S-helix. Conclusion Combining these observations with previously reported mutagenesis studies on different S-helix-containing proteins we suggest that it functions as a switch that prevents constitutive activation of linked downstream signaling domains. However, upon occurrence of specific conformational changes due to binding of ligand or other sensory inputs in a linked upstream domain it transmits the signal to the downstream domain. Thus, the S-helix represents one of the most prevalent functional themes involved in the flow of signals between modules in diverse prokaryote-type multi-domain signaling proteins. Reviewers This article was reviewed by Frank Eisenhaber, Arcady Mushegian and Sandor Pongor. PMID:16953892

Compartmentalization Technologies via Self-Assembly and Cross-Linking of Amphiphilic Random Block Copolymers in Water.

PubMed

Matsumoto, Mayuko; Terashima, Takaya; Matsumoto, Kazuma; Takenaka, Mikihito; Sawamoto, Mitsuo

2017-05-31

Orthogonal self-assembly and intramolecular cross-linking of amphiphilic random block copolymers in water afforded an approach to tailor-make well-defined compartments and domains in single polymer chains and nanoaggregates. For a double compartment single-chain polymer, an amphiphilic random block copolymer bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl, benzyl, and olefin pendants was synthesized by living radical polymerization (LRP) and postfunctionalization; the dodecyl and benzyl units were incorporated into the different block segments, whereas PEG pendants were statistically attached along a chain. The copolymer self-folded via the orthogonal self-assembly of hydrophobic dodecyl and benzyl pendants in water, followed by intramolecular cross-linking, to form a single-chain polymer carrying double yet distinct hydrophobic nanocompartments. A single-chain cross-linked polymer with a chlorine terminal served as a globular macroinitiator for LRP to provide an amphiphilic tadpole macromolecule comprising a hydrophilic nanoparticle and a hydrophobic polymer tail; the tadpole thus self-assembled into multicompartment aggregates in water.

Specific Amyloid Binding of Polybasic Peptides In Vivo Is Retained by β-Sheet Conformers but Lost in the Disrupted Coil and All D-Amino Acid Variants.

PubMed

Wall, Jonathan S; Williams, Angela; Richey, Tina; Stuckey, Alan; Wooliver, Craig; Christopher Scott, J; Donnell, Robert; Martin, Emily B; Kennel, Stephen J

2017-10-01

The heparin-reactive, helical peptide p5 is an effective amyloid imaging agent in mice with systemic amyloidosis. Analogs of p5 with modified secondary structure characteristics exhibited altered binding to heparin, synthetic amyloid fibrils, and amyloid extracts in vitro. Herein, we further study the effects of peptide helicity and chirality on specific amyloid binding using a mouse model of systemic inflammation-associated (AA) amyloidosis. Peptides with disrupted helical structure [p5 (coil) and p5 (Pro3) ], with an extended sheet conformation [p5 (sheet) ] or an all-D enantiomer [p5 (D) ], were chemically synthesized, radioiodinated, and their biodistribution studied in WT mice as well as transgenic animals with severe systemic AA amyloidosis. Peptide binding was assessed qualitatively by using small animal single-photon emission computed tomography/x-ray computed tomography imaging and microautoradiography and quantitatively using tissue counting. Peptides with reduced helical propensity, p5 (coil) and p5 (Pro3) , exhibited significantly reduced binding to AA amyloid-laden organs. In contrast, peptide p5 (D) was retained by non-amyloid-related ligands in the liver and kidneys of both WT and AA mice, but it also bound AA amyloid in the spleen. The p5 (sheet) peptide specifically bound AA amyloid in vivo and was not retained by healthy tissues in WT animals. Modification of amyloid-targeting peptides using D-amino acids should be performed cautiously due to the introduction of unexpected secondary pharmacologic effects. Peptides that adopt a helical structure, to align charged amino acid side chains along one face, exhibit specific reactivity with amyloid; however, polybasic peptides with a propensity for β-sheet conformation are also amyloid-reactive and may yield a novel class of amyloid-targeting agents for imaging and therapy.

Prediction of Long Loops with Embedded Secondary Structure using the Protein Local Optimization Program

PubMed Central

Miller, Edward B.; Murrett, Colleen S.; Zhu, Kai; Zhao, Suwen; Goldfeld, Dahlia A.; Bylund, Joseph H.; Friesner, Richard A.

2013-01-01

Robust homology modeling to atomic-level accuracy requires in the general case successful prediction of protein loops containing small segments of secondary structure. Further, as loop prediction advances to success with larger loops, the exclusion of loops containing secondary structure becomes awkward. Here, we extend the applicability of the Protein Local Optimization Program (PLOP) to loops up to 17 residues in length that contain either helical or hairpin segments. In general, PLOP hierarchically samples conformational space and ranks candidate loops with a high-quality molecular mechanics force field. For loops identified to possess α-helical segments, we employ an alternative dihedral library composed of (ϕ,ψ) angles commonly found in helices. The alternative library is searched over a user-specified range of residues that define the helical bounds. The source of these helical bounds can be from popular secondary structure prediction software or from analysis of past loop predictions where a propensity to form a helix is observed. Due to the maturity of our energy model, the lowest energy loop across all experiments can be selected with an accuracy of sub-Ångström RMSD in 80% of cases, 1.0 to 1.5 Å RMSD in 14% of cases, and poorer than 1.5 Å RMSD in 6% of cases. The effectiveness of our current methods in predicting hairpin-containing loops is explored with hairpins up to 13 residues in length and again reaching an accuracy of sub-Ångström RMSD in 83% of cases, 1.0 to 1.5 Å RMSD in 10% of cases, and poorer than 1.5 Å RMSD in 7% of cases. Finally, we explore the effect of an imprecise surrounding environment, in which side chains, but not the backbone, are initially in perturbed geometries. In these cases, loops perturbed to 3Å RMSD from the native environment were restored to their native conformation with sub-Ångström RMSD. PMID:23814507

Organization of polymer chains onto long, single-wall carbon nano-tubes: effect of tube diameter and cooling method.

PubMed

Kumar, Sunil; Pattanayek, Sudip K; Pereira, Gerald G

2014-01-14

We use molecular dynamics simulations to investigate the arrangement of polymer chains when absorbed onto a long, single-wall carbon nano-tube (SWCNT). We study the conformation and organization of the polymer chains on the SWCNT and their dependence on the tube's diameter and the rate of cooling. We use two types of cooling processes: direct quenching and gradual cooling. The radial density distribution function and bond orientational order parameter are used to characterize the polymer chain structure near the surface. In the direct cooling process, the beads of the polymer chain organize in lamella-like patterns on the surface of the SWCNT with the long axis of the lamella parallel to the axis of the SWCNT. In a stepwise, gradual cooling process, the polymer beads form a helical pattern on the surface of a relatively thick SWCNT, but form a lamella-like pattern on the surface of a very thin SWCNT. We develop a theoretical (free energy) model to explain this difference in pattern structures for the gradual cooling process and also provide a qualitative explanation for the pattern that forms from the direct cooling process.

Variable Asymmetric Chains in Transition Metal Oxyfluorides: Structure-Second-Harmonic-Generation Property Relationships.

PubMed

Ahmed, Belal; Jo, Hongil; Oh, Seung-Jin; Ok, Kang Min

2018-05-15

Four novel transition metal oxyfluorides, [Zn(pz) 3 ][MoO 2 F 4 ]·0.1H 2 O (1), [Zn(pz) 2 F 2 ][Zn(pz) 3 ] 2 [WO 2 F 4 ] 2 (2), [Cd(pz) 4 ][Cd(pz) 4 (H 2 O)][MoO 2 F 4 ] 2 ·0.625H 2 O (3), and [Zn(mpz) 3 ] 2 [MoO 2 F 4 ] 2 (4) (pz = pyrazole; mpz = 3-methyl pyrazole) have been synthesized. Compounds 1 and 4 contain helical chains. Compound 2 accommodates zigzag chains, and compound 3 has quasi-one-dimensional linear chains. The variable chain structures are found to be attributable to the different structure-directing anionic groups and hydrogen bonding interactions. Compound 4 crystallized in the noncentrosymmetric (NCS) polar space group, Pna2 1 , is nonphase-matchable (Type I), and reveals a moderate second-harmonic-generation (SHG) efficiency (10 × α-SiO 2 ). The observed SHG efficiency of compound 4 is due to the small net polarization occurring from the arrangement of ZnN 3 F 2 trigonal bipyramids. Spectroscopic and thermal characterizations along with calculations for the title materials are reported.

Choice between Single and Multiple Reinforcers in Concurrent-Chains Schedules

ERIC Educational Resources Information Center

Mazur, James E.

2006-01-01

Pigeons responded on concurrent-chains schedules with equal variable-interval schedules as initial links. One terminal link delivered a single reinforcer after a fixed delay, and the other terminal link delivered either three or five reinforcers, each preceded by a fixed delay. Some conditions included a postreinforcer delay after the single…

Temporal Context in Concurrent Chains: I. Terminal-Link Duration

ERIC Educational Resources Information Center

Grace, Randolph C.

2004-01-01

Two experiments are reported in which the ratio of the average times spent in the terminal and initial links ("Tt/Ti") in concurrent chains was varied. In Experiment 1, pigeons responded in a three-component procedure in which terminal-link variable-interval schedules were in constant ratio, but their average duration increased across components…

A Novel Algorithm for the Generation of Distinct Kinematic Chain

NASA Astrophysics Data System (ADS)

Medapati, Sreenivasa Reddy; Kuchibhotla, Mallikarjuna Rao; Annambhotla, Balaji Srinivasa Rao

2016-07-01

Generation of distinct kinematic chains is an important topic in the design of mechanisms for various industrial applications i.e., robotic manipulator, tractor, crane etc. Many researchers have intently focused on this area and explained various processes of generating distinct kinematic chains which are laborious and complex. It is desirable to enumerate the kinematic chains systematically to know the inherent characteristics of a chain related to its structure so that all the distinct chains can be analyzed in depth, prior to the selection of a chain for a purpose. This paper proposes a novel and simple method with set of rules defined to eliminate isomorphic kinematic chains generating distinct kinematic chains. Also, this method simplifies the process of generating distinct kinematic chains even at higher levels i.e., 10-link, 11-link with single and multiple degree of freedom.

A Novel Algorithm for the Generation of Distinct Kinematic Chain

NASA Astrophysics Data System (ADS)

Medapati, Sreenivasa Reddy; Kuchibhotla, Mallikarjuna Rao; Annambhotla, Balaji Srinivasa Rao

2018-06-01

Generation of distinct kinematic chains is an important topic in the design of mechanisms for various industrial applications i.e., robotic manipulator, tractor, crane etc. Many researchers have intently focused on this area and explained various processes of generating distinct kinematic chains which are laborious and complex. It is desirable to enumerate the kinematic chains systematically to know the inherent characteristics of a chain related to its structure so that all the distinct chains can be analyzed in depth, prior to the selection of a chain for a purpose. This paper proposes a novel and simple method with set of rules defined to eliminate isomorphic kinematic chains generating distinct kinematic chains. Also, this method simplifies the process of generating distinct kinematic chains even at higher levels i.e., 10-link, 11-link with single and multiple degree of freedom.

Chiral direction and interconnection of helical three-connected networks in metal-organic frameworks.

PubMed

Prior, T J; Rosseinsky, M J

2003-03-10

The control of the interpenetration and chirality of a family of metal-organic frameworks is discussed. These systems contain two- (A) and four-fold (B) interpenetration of helical three-connected networks generated by binding the 1,3,5-benzenetricarboxylate (btc) ligand to a metal center. These frameworks have the general formula Ni(3)(btc)(2)X(m)Y(n).solvent (where X = pyridine or 4-picoline, Y = ethylene glycol, 1,2-propanediol, 1,4-butanediol, meso-2,3-butanediol, 1,2,6-hexanetriol, glycerol). The structural and chemical effects of modifying the alcohol and aromatic amine ligands bound to the metal center include controlling the thermal stability and the degree of interpenetration. Covalent linking of the four interpenetrating networks in the A family and the switching of diol binding from mono- to bidentate are demonstrated. Recognition of chiral diols by the hand of the network helices is investigated by binding an alcohol ligand with two chiral centers of opposite sense to the same helix. This reveals the subtle nature of the helix-ligand interaction.

From Mesocates to Helicates: Structural, Magnetic and Chiro-Optical Studies on Nickel(II) Supramolecular Assemblies Derived from Tetradentate Schiff Bases.

PubMed

Mayans, Júlia; Font-Bardia, Mercè; Di Bari, Lorenzo; Arrico, Lorenzo; Zinna, Francesco; Pescitelli, Gennaro; Escuer, Albert

2018-05-28

The systematic reactions of a family of tetradentate pyridyl/imine and quinolyl/imine racemic or enantiopure Schiff bases with Ni(NO 3 ) 2 or Ni(ClO 4 ) 2 in the presence of sodium azide yielded, as a function of the starting racemic, chiral or achiral base, a set of chiral, meso or achiral complexes. In all cases, the compounds consist of two Ni II cations linked by a double azido bridge in its end-on coordination mode. All the dimers exhibit a mesocate supramolecular structure and one of them, the unprecedented mix of helicate and mesocate in 2:1 ratio. The transition from mesocate to helicate conformation has been reached by tuning the flexibility of the central spacers of the Schiff bases and the size of the substituents. Electronic circular dichroism (ECD) studies have been performed for two pairs of enantiomers and interpreted by means of DFT calculations. Susceptibility measurements show a ferromagnetic coupling between the Ni II cations mediated by the end-on azido bridges. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organization of the mitochondrial apoptotic BAK pore: oligomerization of the BAK homodimers.

PubMed

Aluvila, Sreevidya; Mandal, Tirtha; Hustedt, Eric; Fajer, Peter; Choe, Jun Yong; Oh, Kyoung Joon

2014-01-31

The multidomain pro-apoptotic Bcl-2 family proteins BAK and BAX are believed to form large oligomeric pores in the mitochondrial outer membrane during apoptosis. Formation of these pores results in the release of apoptotic factors including cytochrome c from the intermembrane space into the cytoplasm, where they initiate the cascade of events that lead to cell death. Using the site-directed spin labeling method of electron paramagnetic resonance (EPR) spectroscopy, we have determined the conformational changes that occur in BAK when the protein targets to the membrane and forms pores. The data showed that helices α1 and α6 disengage from the rest of the domain, leaving helices α2-α5 as a folded unit. Helices α2-α5 were shown to form a dimeric structure, which is structurally homologous to the recently reported BAX "BH3-in-groove homodimer." Furthermore, the EPR data and a chemical cross-linking study demonstrated the existence of a hitherto unknown interface between BAK BH3-in-groove homodimers in the oligomeric BAK. This novel interface involves the C termini of α3 and α5 helices. The results provide further insights into the organization of the BAK oligomeric pores by the BAK homodimers during mitochondrial apoptosis, enabling the proposal of a BAK-induced lipidic pore with the topography of a "worm hole."

Crystal and Molecular Structure of a Collagen-Like Peptide at 1.9 overset{circ}{A} Resolution

NASA Astrophysics Data System (ADS)

Bella, Jordi; Eaton, Mark; Brodsky, Barbara; Berman, Helen M.

1994-10-01

The structure of a protein triple helix has been determined at 1.9 angstrom resolution by x-ray crystallographic studies of a collagen-like peptide containing a single substitution of the consensus sequence. This peptide adopts a triple-helical structure that confirms the basic features determined from fiber diffraction studies on collagen: supercoiling of polyproline II helices and interchain hydrogen bonding that follows the model II of Rich and Crick. In addition, the structure provides new information concerning the nature of this protein fold. Each triple helix is surrounded by a cylinder of hydration, with an extensive hydrogen bonding network between water molecules and peptide acceptor groups. Hydroxyproline residues have a critical role in this water network. The interaxial spacing of triple helices in the crystal is similar to that in collagen fibrils, and the water networks linking adjacent triple helices in the crystal structure are likely to be present in connective tissues. The breaking of the repeating (X-Y-Gly)_n pattern by a Gly-->Ala substitution results in a subtle alteration of the conformation, with a local untwisting of the triple helix. At the substitution site, direct interchain hydrogen bonds are replaced with interstitial water bridges between the peptide groups. Similar conformational changes may occur in Gly-->X mutated collagens responsible for the diseases osteogenesis imperfecta, chondrodysplasias, and Ehlers-Danlos syndrome IV.

Flow structures and sandbar dynamics in a canyon river during a controlled flood, Colorado River, Arizona

USGS Publications Warehouse

Wright, S.A.; Kaplinski, M.

2011-01-01

In canyon rivers, debris fan constrictions create rapids and downstream pools characterized by secondary flow structures that are closely linked to channel morphology. In this paper we describe detailed measurements of the three-dimensional flow structure and sandbar dynamics of two pools along the Colorado River in the Grand Canyon during a controlled flood release from Glen Canyon Dam. Results indicate that the pools are characterized by large lateral recirculation zones (eddies) resulting from flow separation downstream from the channel constrictions, as well as helical flow structures in the main channel and eddy. The lateral recirculation zones are low-velocity areas conducive to fine sediment deposition, particularly in the vicinity of the separation and reattachment points and are thus the dominant flow structures controlling sandbar dynamics. The helical flow structures also affect morphology but appear secondary in importance to the lateral eddies. During the controlled flood, sandbars in the separation and reattachment zones at both sites tended to build gradually during the rising limb and peak flow. Deposition in shallow water on the sandbars was accompanied by erosion in deeper water along the sandbar slope at the interface with the main channel. Erosion occurred via rapid mass failures as well as by gradual boundary shear stress driven processes. The flow structures and morphologic links at our study sites are similar to those identified in other river environments, in particular sharply curved meanders and channel confluences where the coexistence of lateral recirculation and helical flows has been documented. Copyright 2011 by the American Geophysical Union.

A Thumbwheel Mechanism for APOA1 Activation of LCAT Activity in HDL.

PubMed

Cooke, Allison L; Morris, Jamie; Melchior, John T; Street, Scott E; Jerome, W Gray; Huang, Rong; Herr, Andrew B; Smith, Loren E; Segrest, Jere P; Remaley, Alan T; Shah, Amy S; Thompson, Thomas B; Davidson, W Sean

2018-05-17

APOA1 is the most abundant protein in HDL. It modulates interactions that affect HDLs cardioprotective functions, in part via its activation of the enzyme LCAT. On nascent, discoidal HDL, APOA1 comprises 10 alpha-helical repeats arranged in an anti-parallel, stacked-ring structure that encapsulates a lipid bilayer. Previous chemical cross-linking studies suggested that these APOA1 rings can adopt at least two different orientations, or registries, with respect to each other; however, the functional impact of these structural changes is unknown. Here, we placed Cys-residues at locations predicted to form disulfide bonds in each orientation and then measured APOA1s ability to adopt the two registries during HDL particle formation. We found that most APOA1 oriented with the fifth helix of one molecule across from fifth helix of the other (5/5 helical registry), but a fraction adopted a 5/2 registry. Engineered HDL that were locked in 5/5 or 5/2 registries by disulfide bonds equally promoted cholesterol efflux from macrophages - indicating functional particles. However, unlike the 5/5 registry or the wild-type, the 5/2 registry impaired LCAT cholesteryl esterification activity (p<0.001), despite LCAT binding equally to all particles. Chemical cross-linking studies suggest that full LCAT activity requires a hybrid epitope composed of helices 5-7 on one APOA1 molecule and 3-4 on the other. Thus, APOA1 may use a reciprocating, thumbwheel-like mechanism to activate HDL-remodeling proteins. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Lipid-peptide-polymer conjugates and nanoparticles thereof

DOEpatents

Xu, Ting; Dong, He; Shu, Jessica

2015-06-02

The present invention provides a conjugate having a peptide with from about 10 to about 100 amino acids, wherein the peptide adopts a helical structure. The conjugate also includes a first polymer covalently linked to the peptide, and a hydrophobic moiety covalently linked to the N-terminus of the peptide, wherein the hydrophobic moiety comprises a second polymer or a lipid moiety. The present invention also provides helix bundles form by self-assembling the conjugates, and particles formed by self-assembling the helix bundles. Methods of preparing the helix bundles and particles are also provided.

Self assembling proteins

DOEpatents

Yeates, Todd O.; Padilla, Jennifer; Colovos, Chris

2004-06-29

Novel fusion proteins capable of self-assembling into regular structures, as well as nucleic acids encoding the same, are provided. The subject fusion proteins comprise at least two oligomerization domains rigidly linked together, e.g. through an alpha helical linking group. Also provided are regular structures comprising a plurality of self-assembled fusion proteins of the subject invention, and methods for producing the same. The subject fusion proteins find use in the preparation of a variety of nanostructures, where such structures include: cages, shells, double-layer rings, two-dimensional layers, three-dimensional crystals, filaments, and tubes.

[Healthcare value chain: a model for the Brazilian healthcare system].

PubMed

Pedroso, Marcelo Caldeira; Malik, Ana Maria

2012-10-01

This article presents a model of the healthcare value chain which consists of a schematic representation of the Brazilian healthcare system. The proposed model is adapted for the Brazilian reality and has the scope and flexibility for use in academic activities and analysis of the healthcare sector in Brazil. It places emphasis on three components: the main activities of the value chain, grouped in vertical and horizontal links; the mission of each link and the main value chain flows. The proposed model consists of six vertical and three horizontal links, amounting to nine. These are: knowledge development; supply of products and technologies; healthcare services; financial intermediation; healthcare financing; healthcare consumption; regulation; distribution of healthcare products; and complementary and support services. Four flows can be used to analyze the value chain: knowledge and innovation; products and services; financial; and information.

Value of Conditioned Reinforcers as a Function of Temporal Context

ERIC Educational Resources Information Center

O'Daly, Matthew; Meyer, Steven; Fantino, Edmund

2005-01-01

In two experiments, pigeons were trained on a multiple-chain schedule, in which the initial link for one chain was a variable-interval (VI) 100s schedule and for the other chain a VI 10s schedule. The terminal links were both fixed-time 30s schedules signaled by differently colored stimuli. Following training, the pigeons had their preference for…

The Falling Chain of Hopkins, Tait, Steele and Cayley

ERIC Educational Resources Information Center

Wong, Chun Wa; Youn, Seo Ho; Yasui, Kosuke

2007-01-01

A uniform, flexible and frictionless chain falling link by link from a heap by the edge of a table falls with an acceleration g/3 if the motion is nonconservative, but g/2 if the motion is conservative, g being the acceleration due to gravity. Unable to construct such a falling chain, we use instead higher-dimensional versions of it. A home…

O2 sensing-associated glycosylation exposes the F-box-combining site of the Dictyostelium Skp1 subunit in E3 ubiquitin ligases.

PubMed

Sheikh, M Osman; Thieker, David; Chalmers, Gordon; Schafer, Christopher M; Ishihara, Mayumi; Azadi, Parastoo; Woods, Robert J; Glushka, John N; Bendiak, Brad; Prestegard, James H; West, Christopher M

2017-11-17

Skp1 is a conserved protein linking cullin-1 to F-box proteins in SCF ( S kp1/ C ullin-1/ F -box protein) E3 ubiquitin ligases, which modify protein substrates with polyubiquitin chains that typically target them for 26S proteasome-mediated degradation. In Dictyostelium (a social amoeba), Toxoplasma gondii (the agent for human toxoplasmosis), and other protists, Skp1 is regulated by a unique pentasaccharide attached to hydroxylated Pro-143 within its C-terminal F-box-binding domain. Prolyl hydroxylation of Skp1 contributes to O 2 -dependent Dictyostelium development, but full glycosylation at that position is required for optimal O 2 sensing. Previous studies have shown that the glycan promotes organization of the F-box-binding region in Skp1 and aids in Skp1's association with F-box proteins. Here, NMR and MS approaches were used to determine the glycan structure, and then a combination of NMR and molecular dynamics simulations were employed to characterize the impact of the glycan on the conformation and motions of the intrinsically flexible F-box-binding domain of Skp1. Molecular dynamics trajectories of glycosylated Skp1 whose calculated monosaccharide relaxation kinetics and rotational correlation times agreed with the NMR data indicated that the glycan interacts with the loop connecting two α-helices of the F-box-combining site. In these trajectories, the helices separated from one another to create a more accessible and dynamic F-box interface. These results offer an unprecedented view of how a glycan modification influences a disordered region of a full-length protein. The increased sampling of an open Skp1 conformation can explain how glycosylation enhances interactions with F-box proteins in cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

De novo design of peptide immunogens that mimic the coiled coil region of human T-cell leukemia virus type-1 glycoprotein 21 transmembrane subunit for induction of native protein reactive neutralizing antibodies.

PubMed

Sundaram, Roshni; Lynch, Marcus P; Rawale, Sharad V; Sun, Yiping; Kazanji, Mirdad; Kaumaya, Pravin T P

2004-06-04

Peptide vaccines able to induce high affinity and protective neutralizing antibodies must rely in part on the design of antigenic epitopes that mimic the three-dimensional structure of the corresponding region in the native protein. We describe the design, structural characterization, immunogenicity, and neutralizing potential of antibodies elicited by conformational peptides derived from the human T-cell leukemia virus type 1 (HTLV-1) gp21 envelope glycoprotein spanning residues 347-374. We used a novel template design and a unique synthetic approach to construct two peptides (WCCR2T and CCR2T) that would each assemble into a triple helical coiled coil conformation mimicking the gp21 crystal structure. The peptide B-cell epitopes were grafted onto the epsilon side chains of three lysyl residues on a template backbone construct consisting of the sequence acetyl-XGKGKGKGCONH2 (where X represents the tetanus toxoid promiscuous T cell epitope (TT) sequence 580-599). Leucine substitutions were introduced at the a and d positions of the CCR2T sequence to maximize helical character and stability as shown by circular dichroism and guanidinium hydrochloride studies. Serum from an HTLV-1-infected patient was able to recognize the selected epitopes by enzyme-linked immunosorbent assay (ELISA). Mice immunized with the wild-type sequence (WCCR2T) and the mutant sequence (CCR2T) elicited high antibody titers that were capable of recognizing the native protein as shown by flow cytometry and whole virus ELISA. Sera and purified antibodies from immunized mice were able to reduce the formation of syncytia induced by the envelope glycoprotein of HTLV-1, suggesting that antibodies directed against the coiled coil region of gp21 are capable of disrupting cell-cell fusion. Our results indicate that these peptides represent potential candidates for use in a peptide vaccine against HTLV-1.

Novel Crystal Structure C60 Nanowire

NASA Astrophysics Data System (ADS)

Mickelson, William; Aloni, Shaul; Han, Weiqiang; Cumings, John; Zettl, Alex

2003-03-01

We have created insulated C60 nanowire by packing C60 molecules into the interior of insulating boron nitride (BN) nanotubes. For small-diameter BN tubes, the wire consists of a linear chain of C60's. With increasing BN tube inner diameter, novel C60 stacking configurations are obtained (including helical, hollow core, and incommensurate) which are unknown for bulk or thin film forms of C60. C60 in BN nanotubes presents a model system for studying the properties of new dimensionally-constrained "silo" crystal structures.

Transmembrane Polyproline Helix.

PubMed

Kubyshkin, Vladimir; Grage, Stephan L; Bürck, Jochen; Ulrich, Anne S; Budisa, Nediljko

2018-05-03

The third most abundant polypeptide conformation in nature, the polyproline-II helix, is a polar, extended secondary structure with a local organization stabilized by intercarbonyl interactions within the peptide chain. Here we design a hydrophobic polyproline-II helical peptide based on an oligomeric octahydroindole-2-carboxylic acid scaffold and demonstrate its transmembrane alignment in model lipid bilayers by means of solid-state 19 F NMR. As result, we provide a first example of a purely artificial transmembrane peptide with a structural organization that is not based on hydrogen-bonding.

Role of special cross-links in structure formation of bacterial DNA polymer

NASA Astrophysics Data System (ADS)

Agarwal, Tejal; Manjunath, G. P.; Habib, Farhat; Lakshmi Vaddavalli, Pavana; Chatterji, Apratim

2018-01-01

Using data from contact maps of the DNA-polymer of Escherichia coli (E. Coli) (at kilobase pair resolution) as an input to our model, we introduce cross-links between monomers in a bead-spring model of a ring polymer at very specific points along the chain. Via suitable Monte Carlo simulations, we show that the presence of these cross-links leads to a particular organization of the chain at large (micron) length scales of the DNA. We also investigate the structure of a ring polymer with an equal number of cross-links at random positions along the chain. We find that though the polymer does get organized at the large length scales, the nature of the organization is quite different from the organization observed with cross-links at specific biologically determined positions. We used the contact map of E. Coli bacteria which has around 4.6 million base pairs in a single circular chromosome. In our coarse-grained flexible ring polymer model, we used 4642 monomer beads and observed that around 80 cross-links are enough to induce the large-scale organization of the molecule accounting for statistical fluctuations caused by thermal energy. The length of a DNA chain even of a simple bacterial cell such as E. Coli is much longer than typical proteins, hence we avoided methods used to tackle protein folding problems. We define new suitable quantities to identify the large scale structure of a polymer chain with a few cross-links.

Quantum phase transition and protected ideal transport in a Kondo chain

DOE PAGES

Tsvelik, A. M.; Yevtushenko, O. M.

2015-11-30

We study the low energy physics of a Kondo chain where electrons from a one-dimensional band interact with magnetic moments via an anisotropic exchange interaction. It is demonstrated that the anisotropy gives rise to two different phases which are separated by a quantum phase transition. In the phase with easy plane anisotropy, Z2 symmetry between sectors with different helicity of the electrons is broken. As a result, localization effects are suppressed and the dc transport acquires (partial) symmetry protection. This effect is similar to the protection of the edge transport in time-reversal invariant topological insulators. The phase with easy axismore » anisotropy corresponds to the Tomonaga-Luttinger liquid with a pronounced spin-charge separation. The slow charge density wave modes have no protection against localizatioin.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aaboud, M.; Aad, G.; Abbott, B.

The analysis of the momentum difference between charged hadrons in high-energy proton-proton collisions is performed in order to study coherent particle production. The observed correlation pattern agrees with a model of a helical QCD string fragmenting into a chain of ground-state hadrons. A threshold momentum difference in the production of adjacent pairs of charged hadrons is observed, in agreement with model predictions. The presence of low-mass hadron chains also explains the emergence of charge-combination-dependent two-particle correlations commonly attributed to Bose-Einstein interference. Here, the data sample consists of 190 μb –1 of minimum-bias events collected with proton-proton collisions at a center-of-massmore » energy √s=7 TeV in the early low-luminosity data taking with the ATLAS detector at the LHC.« less

Solution of the Lindblad equation for spin helix states.

PubMed

Popkov, V; Schütz, G M

2017-04-01

Using Lindblad dynamics we study quantum spin systems with dissipative boundary dynamics that generate a stationary nonequilibrium state with a nonvanishing spin current that is locally conserved except at the boundaries. We demonstrate that with suitably chosen boundary target states one can solve the many-body Lindblad equation exactly in any dimension. As solution we obtain pure states at any finite value of the dissipation strength and any system size. They are characterized by a helical stationary magnetization profile and a ballistic spin current which is independent of system size, even when the quantum spin system is not integrable. These results are derived in explicit form for the one-dimensional spin-1/2 Heisenberg chain and its higher-spin generalizations, which include the integrable spin-1 Zamolodchikov-Fateev model and the biquadratic Heisenberg chain.

Flexibility of "polyunsaturated fatty acid chains" and peptide backbones: A comparative ab initio study.

PubMed

Law, Jacqueline M S; Setiadi, David H; Chass, Gregory A; Csizmadia, Imre G; Viskolcz, Béla

2005-01-27

The conformational properties of omega-3 type of polyunsaturated fatty acid (PUFA) chains and their fragments were studied using Hartree-Fock (RHF/3-21G) and DFT (B3LYP/6-31G(d)) methods. Comparisons between a unit (U) fragment of the PUFA chain and a mono N-Ac-glycine-NHMe residue show that both structures have the same sequence of sp2-sp3-sp2 atoms. The flexibility of PUFA originates in the internal rotation about the above pairs of sigma bonds. Therefore, potential energy surfaces (PESs) were generated by a scan around the terminal dihedral angles (phi t1 and phi t2) as well as the phi 1 and psi 1 dihedrals of both 1U congeners (Me-CHCH-CH2-CHCHMe and MeCONH-CH2-CONHMe) at the RHF/3-21G level of theory. An interesting similarity was found in the flexibility between the cis allylic structure and the trans peptide models. A flat landscape can be seen in the cis 1U (hepta-2,5-diene) surface, implying that several conformations are expected to be found in this (PES). An exhaustive search carried out on the 1U and 2U models revealed that straight chain structures such as trans and cis beta (phi 1 approximately psi 1 approximately 120 degrees; phi 2 approximately psi 2 approximately -120 degrees) or trans and cis extended (phi 1 approximately psi 1 approximately phi 2 approximately psi 2 approximately 120 degrees) can be formed at the lowest energy of both isomers. However, forming helical structures, such as trans helix (phi 1 approximately -120 degrees, psi 1 approximately 12 degrees; phi 2 approximately -120 degrees, psi 2 approximately 12 degrees) or cis helix (phi 1 approximately -130 degrees, psi 1 approximately 90 degrees; phi 2 approximately -145 degrees, psi 2 approximately 90 degrees) will require more energy. These six conformations, found in 2U, were selected to construct longer chains such as 3U, 4U, 5U, and 6U to obtain the thermochemistry of secondary structures. The variation in the extension or compression of the chain length turned out to be a factor of 2 between the helical and nonhelical structures. The inside diameter of the "tube" of cis helix turned out to be 3.5 A after discounting the internal H atoms. Thermodynamic functions were computed at the B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d). The cis-trans isomerization energy of 1.7 +/- 0.2 kcal mol(-1) unit(-1) for all structure pairs indicates that the conformer selection was consistent. A folding energy of 0.5 +/- 0.1 kcal mol(-1) unit(-1) has been extracted from the energy comparison of the helices and most extended nonhelical structures. The entropy change associated with the folding (Delta S(folding)) is decreases faster with the degree of polymerization (n) for the cis than for the trans isomer. As a consequence, the linear relationships between (Delta G(folding)) and n for the cis and trans isomer crossed at about n = 3. This suggested that the naturally occurring cis isomer less ready to fold than the trans isomer since a greater degree of organization is exhibited by the cis isomer during the folding process. The result of this work leads to the question within the group additivity rule: could the method applied in our study of the folding of polyallylic hydrocarbons be useful in investigating the thermochemistry of protein folding?

Motion of spin label side chains in cellular retinol-binding protein: correlation with structure and nearest-neighbor interactions in an antiparallel beta-sheet.

PubMed

Lietzow, Michael A; Hubbell, Wayne L

2004-03-23

A goal in the development of site-directed spin labeling in proteins is to correlate the motion of a nitroxide side chain with local structure, interactions, and dynamics. Significant progress toward this goal has been made using alpha-helical proteins of known structure, and the present study is the first step in a similar exploration of a beta-sheet protein, cellular retinol-binding protein (CRBP). Nitroxide side chains were introduced along both interior and edge strands. At sites in interior strands, the side-chain motion is strongly influenced by interactions with side chains of neighboring strands, giving rise to a rich variety of dynamic modes (weakly ordered, strongly ordered, immobilized) and complex electron paramagnetic resonance spectra that are modulated by strand twist. The interactions giving rise to the dynamic modes are explored using mutagenesis, and the results demonstrate the particular importance of the non-hydrogen-bonded neighbor residue in giving rise to highly ordered states. Along edge strands of the beta-sheet, the motion of the side chain is simple and weakly ordered, resembling that at solvent-exposed surfaces of an alpha-helix. A simple working model is proposed that can account for the wide variety of dynamic modes encountered. Collectively, the results suggest that the nitroxide side chain is an effective probe of side-chain interactions, and that site-directed spin labeling should be a powerful means of monitoring conformational changes that involve changes in beta-sheet topology.

Profiling of ornithine lipids in bacterial extracts of Rhodobacter sphaeroides by reversed-phase liquid chromatography with electrospray ionization and multistage mass spectrometry (RPLC-ESI-MS(n)).

PubMed

Granafei, Sara; Losito, Ilario; Trotta, Massimo; Italiano, Francesca; de Leo, Vincenzo; Agostiano, Angela; Palmisano, Francesco; Cataldi, Tommaso R I

2016-01-15

Ornithine lipids (OLs), a sub-group of the large (and of emerging interest) family of lipoamino acids of bacterial origin, contain a 3-hydroxy fatty acyl chain linked via an amide bond to the α-amino group of ornithine and via an ester bond to a second fatty acyl chain. OLs in extracts of Rhodobacter sphaeroides (R. sphaeroides) were investigated by high-performance reversed phase liquid chromatography (RPLC) with electrospray ionization mass spectrometry (ESI-MS) in negative ion mode using a linear ion trap (LIT). The presence of OLs bearing both saturated (i.e, 16:0, 17:0, 18:0, 19:0 and 20:0) and unsaturated chains (i.e., 18:1, 19:1, 19:2 and 20:1) was ascertained and their identification, even for isomeric, low abundance and partially co-eluting species, was achieved by low-energy collision induced dissociation (CID) multistage mass spectrometry (MS(n), n = 2-4). OLs signatures found in two R. sphaeroides strains, i.e., wild type 2.4.1 and mutant R26, were examined and up to 16 and 17 different OL species were successfully identified, respectively. OLs in both bacterial strains were characterized by several combinations of fatty chains on ester-linked and amide-linked 3-OH fatty acids. Multistage MS spectra of monoenoic amide-linked 3-OH acyl chains, allowed the identification of positional isomer of OL containing 18:1 (i.e. 9-octadecenoic) and 20:1 (i.e. 11-eicosenoic) fatty acids. The most abundant OL ([M-H](-) at m/z 717.5) in R. sphaeroides R26 was identified as OL 3-OH 20:1/19:1 (i.e., 3-OH-eicosenoic acid amide-linked to ornithine and esterified to a nonadecenoic chain containing a cyclopropane ring). An unusual OL (m/z 689.5 for the [M-H](-) ion), most likely containing a cyclopropene ester-linked acyl chain (i.e., OL 3-OH 18:0/19:2), was retrieved only in the carotenoidless mutant strain R26. Based on the biosynthetic pathways already known for cyclopropa(e)ne ring-including acyl chains, a plausible explanation was invoked for the enzymatic generation of this ester-linked chain in R. sphaeroides. Copyright © 2015 Elsevier B.V. All rights reserved.

Silver baits for the "miraculous draught" of amphiphilic lanthanide helicates.

PubMed

Terazzi, Emmanuel; Guénée, Laure; Varin, Johan; Bocquet, Bernard; Lemonnier, Jean-François; Emery, Daniel; Mareda, Jiri; Piguet, Claude

2011-01-03

The axial connection of flexible thioalkyls chains of variable length (n=1-12) within the segmental bis-tridentate 2-benzimidazole-8-hydroxyquinoline ligands [L12(Cn) -2 H](2-) provides amphiphilic receptors designed for the synthesis of neutral dinuclear lanthanides helicates. However, the stoichiometric mixing of metals and ligands in basic media only yields intricate mixtures of poorly soluble aggregates. The addition of Ag(I) in solution restores classical helicate architectures for n=3, with the quantitative formation of the discrete D(3) -symmetrical [Ln(2) Ag2(L12(C3) -2 H)(3) ](2+) complexes at millimolar concentration (Ln=La, Eu, Lu). The X-ray crystal structure supports the formation of [La(2) Ag(2) (L12(C3) -2 H)(3) ][OTf](2) , which exists in the solid state as infinite linear polymers bridged by S-Ag-S bonds. In contrast, molecular dynamics (MD) simulations in the gas phase and in solution confirm the experimental diffusion measurements, which imply the formation of discrete molecular entities in these media, in which the sulfur atoms of each lipophilic ligand are rapidly exchanged within the Ag(I) coordination sphere. Turned as a predictive tool, MD suggests that this Ag(I) templating effect is efficient only for n=1-3, while for n>3 very loose interactions occur between Ag(I) and the thioalkyl residues. The subsequent experimental demonstration that only 25 % of the total ligand speciation contributes to the formation of [Ln(2) Ag(2) (L12(C12) -2 H)(3) ](2+) in solution puts the bases for a rational approach for the design of amphiphilic helical complexes with predetermined molecular interfaces. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The critical main-chain length for helix formation in water: determined in a peptide series with alternating Aib and Ala residues exclusively and detected with ECD spectroscopy.

PubMed

Longo, Edoardo; Moretto, Alessandro; Formaggio, Fernando; Toniolo, Claudio

2011-10-01

Critical main-chain length for peptide helix formation in the crystal (solid) state and in organic solvents has been already reported. In this short communication, we describe our results aiming at assessing the aforementioned parameter in water solution. To this goal, we synthesized step-by-step by solution procedures a complete series of N-terminally acetylated, C-terminally methoxylated oligopeptides, characterized only by alternating Aib and Ala residues, from the dimer to the nonamer level. All these compounds were investigated by electronic circular dichroism in the far-UV region in water solution as a function of chemical structure, namely presence/absence of an ester moiety or a negative charge at the C-terminus, and temperature. We find that the critical main-chain lengths for 3(10)- and α-helices, although still formed to a limited extent, in aqueous solution are six and eight residues, respectively. © 2011 Wiley-Liss, Inc.

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling

PubMed Central

Su, Ting; Cheng, Jingdong; Sohmen, Daniel; Hedman, Rickard; Berninghausen, Otto; von Heijne, Gunnar; Wilson, Daniel N; Beckmann, Roland

2017-01-01

Interaction between the nascent polypeptide chain and the ribosomal exit tunnel can modulate the rate of translation and induce translational arrest to regulate expression of downstream genes. The ribosomal tunnel also provides a protected environment for initial protein folding events. Here, we present a 2.9 Å cryo-electron microscopy structure of a ribosome stalled during translation of the extremely compacted VemP nascent chain. The nascent chain forms two α-helices connected by an α-turn and a loop, enabling a total of 37 amino acids to be observed within the first 50–55 Å of the exit tunnel. The structure reveals how α-helix formation directly within the peptidyltransferase center of the ribosome interferes with aminoacyl-tRNA accommodation, suggesting that during canonical translation, a major role of the exit tunnel is to prevent excessive secondary structure formation that can interfere with the peptidyltransferase activity of the ribosome. DOI: http://dx.doi.org/10.7554/eLife.25642.001 PMID:28556777

Supercoil Formation During DNA Melting

NASA Astrophysics Data System (ADS)

Sayar, Mehmet; Avsaroglu, Baris; Kabakcioglu, Alkan

2009-03-01

Supercoil formation plays a key role in determining the structure-function relationship in DNA. Biological and technological processes, such as protein synthesis, polymerase chain reaction, and microarrays relys on separation of the two strands in DNA, which is coupled to the unwinding of the supercoiled structure. This problem has been studied theoretically via Peyrard-Bishop and Poland-Scheraga type models, which include a simple representation of the DNA structural properties. In recent years, computational models, which provide a more realtistic representaion of DNA molecule, have been used to study the melting behavior of short DNA chains. Here, we will present a new coarse-grained model of DNA which is capable of simulating sufficiently long DNA chains for studying the supercoil formation during melting, without sacrificing the local structural properties. Our coarse-grained model successfully reproduces the local geometry of the DNA molecule, such as the 3'-5' directionality, major-minor groove structure, and the helical pitch. We will present our initial results on the dynamics of supercoiling during DNA melting.

Cross-linking of type I collagen with microbial transglutaminase: identification of cross-linking sites.

PubMed

Stachel, Ines; Schwarzenbolz, Uwe; Henle, Thomas; Meyer, Michael

2010-03-08

Collagen is a popular biomaterial. To deal with its lack of thermal stability and its weak resistance to proteolytic degradation, collagen-based materials are stabilized via different cross-linking procedures. Regarding the potential toxicity of residual cross-linking agents, enzyme-mediated cross-linking would provide an alternative and nontoxic method for collagen stabilization. The results of this study show that type I collagen is a substrate for mTG. However, epsilon-(gamma-glutamyl)lysine cross-links are only incorporated at elevated temperatures when the protein is partially or completely denatured. A maximum number of 5.4 cross-links per collagen monomer were found for heat-denatured collagen. Labeling with the primary amine monodansylcadaverine revealed that at least half of the cross-links are located within the triple helical region of the collagen molecule. Because the triple helix is highly ordered in its native state, this finding might explain why the glutamine residues are inaccessible for mTG under nondenaturing conditions.

[Suffering pain in segment lumbar spine and occurrence of weak links of biokinematics chain in kayakers and rowers].

PubMed

Wójcik, Małgorzata; Siatkowski, Idzi

2011-01-01

Spine pain is a serious clinical problem of physically active people and sportplayers . The pain may have different nature, related to different segments of the spine. Its intensity and frequency may impair the functionality of man. Most back pain is connected with the lumbo-sacral and cervical part of a spine. MAIN AIM: The hypothesis was: 1) That there were not any weak links of biokinematics chain. 2) Pain feeling in young players in the lumbar spine (LBP). The aim of this study was to determine in which direction and location the most weak links would occur in biokinematics chain and whether it was correlated with gender. In addition, it was examined whether a correlation between the weak links' presence in the lumbar spine and the occurrence of LBP existed and if it was connected with gender of the player. This study involved 40 players from Walcz School Sports Championships, including the twenty kayakers (8 women and 12 men), 13 canoeists and 7 rowers. The average age of players was 16.00 +/- 0.99, mean of training years was 4.92 +/- 2.20. Low threshold Performance Matrix tests were used for assessing the presence of weak links. Through analysis and identification of performed movement the weakest links in the biokinetics chain were found. Numeric scale was used for the evaluation of lumbar pain (LBP). The results were statistically analyzed. The main characteristics of statistical and graphical presentations were performed for the received values of weak links. The hypothesis of variances equality was verified, and all the hypotheses mentioned above were also verified using ANOVA analysis of variations and Tukey test for low threshold of weak links. 1) The presence of weak links of biokinematics chain was found in all players especially in the lumbar spine, the presence is not associated with gender. Most weak links in the lumbar part occurred in the direction of rotation. 2) There is a correlation of the weak links of the lumbar spine and LBP, but it is not connected with gender. 3) The relationship between pain suffering in the lumbar spine (LBP) and the number of weak links of biokinematics chain was defined.

The resonant state at filling factor ν = 1/2 in chiral fermionic ladders

NASA Astrophysics Data System (ADS)

Haller, Andreas; Rizzi, Matteo; Burrello, Michele

2018-05-01

Helical liquids have been experimentally realized in both nanowires and ultracold atomic chains as the result of strong spin–orbit interactions. In both cases the inner degrees of freedom can be considered as an additional space dimension, providing an interpretation of these systems as chiral synthetic ladders, with artificial magnetic fluxes determined by the spin–orbit terms. In this work, we characterize the helical state which appears at filling ν = 1/2: this state is generated by a gap arising in the spin sector of the corresponding Luttinger liquid and it can be interpreted as the one-dimensional (1D) limit of a fractional quantum Hall state of bosonic pairs of fermions. We study its main features, focusing on entanglement properties and correlation functions. The techniques developed here provide a key example for the study of similar quasi-1D systems beyond the semiclassical approximation commonly adopted in the description of the Laughlin-like states.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Follis, Kathryn E.; York, Joanne; Nunberg, Jack H.

The fusion subunit of the SARS-CoV S glycoprotein contains two regions of hydrophobic heptad-repeat amino acid sequences that have been shown in biophysical studies to form a six-helix bundle structure typical of the fusion-active core found in Class I viral fusion proteins. Here, we have applied serine-scanning mutagenesis to the C-terminal-most heptad-repeat region in the SARS-CoV S glycoprotein to investigate the functional role of this region in membrane fusion. We show that hydrophobic sidechains at a and d positions only within the short helical segment of the C-terminal heptad-repeat region (I1161, I1165, L1168, A1172, and L1175) are critical for cell-cellmore » fusion. Serine mutations at outlying heptad-repeat residues that form an extended chain in the core structure (V1158, L1179, and L1182) do not affect fusogenicity. Our study provides genetic evidence for the important role of {alpha}-helical packing in promoting S glycoprotein-mediated membrane fusion.« less

The selective autophagy receptor p62 forms a flexible filamentous helical scaffold.

PubMed

Ciuffa, Rodolfo; Lamark, Trond; Tarafder, Abul K; Guesdon, Audrey; Rybina, Sofia; Hagen, Wim J H; Johansen, Terje; Sachse, Carsten

2015-05-05

The scaffold protein p62/SQSTM1 is involved in protein turnover and signaling and is commonly found in dense protein bodies in eukaryotic cells. In autophagy, p62 acts as a selective autophagy receptor that recognizes and shuttles ubiquitinated proteins to the autophagosome for degradation. The structural organization of p62 in cellular bodies and the interplay of these assemblies with ubiquitin and the autophagic marker LC3 remain to be elucidated. Here, we present a cryo-EM structural analysis of p62. Together with structures of assemblies from the PB1 domain, we show that p62 is organized in flexible polymers with the PB1 domain constituting a helical scaffold. Filamentous p62 is capable of binding LC3 and addition of long ubiquitin chains induces disassembly and shortening of filaments. These studies explain how p62 assemblies provide a large molecular scaffold for the nascent autophagosome and reveal how they can bind ubiquitinated cargo. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Polyoxometalates-based chiral frameworks involving helical motifs generated by spontaneous resolution

NASA Astrophysics Data System (ADS)

Li, Ning; Jiang, Dingding; Pan, Qiliang; Zhao, Jianguo; Zhang, Sufang; Xing, Baoyan; Du, Yaqin; Zhang, Zhong; Liu, Shuxia

2018-05-01

Two enantiomerically 3D chiral polyoxometalate frameworks L,D-[K(H2O)]6[H2GeMo2W10O40]3ṡ40H2O (1a and 1b), were conventionally synthesized and characterized by X-ray single-crystal diffraction, IR spectrum, elemental analysis, powder X-ray diffraction, thermogravimetric analysis, UV-Vis spectroscopy, circular dichroism spectra. Structural analysis indicates that 1a and 1b are enantiomers. The terminal O and μ2-O atoms of Keggin-type polyanion [GeMo2W10O40]4- and {K(H2O)}n segments are connected one another to form 1D chiral helical chains, which are further extended by the achiral Keggin-type [GeMo2W10O40]4- anion to construct 3D 4,8-connected chiral frameworks. The enantiomers were isolated by spontaneous resolution during crystallization without any chiral auxiliary. They represent rare examples of enantiomerically pure chiral polyoxometalate-based inorganic porous frameworks.

Four-stranded mini microtubules formed by Prosthecobacter BtubAB show dynamic instability.

PubMed

Deng, Xian; Fink, Gero; Bharat, Tanmay A M; He, Shaoda; Kureisaite-Ciziene, Danguole; Löwe, Jan

2017-07-18

Microtubules, the dynamic, yet stiff hollow tubes built from αβ-tubulin protein heterodimers, are thought to be present only in eukaryotic cells. Here, we report a 3.6-Å helical reconstruction electron cryomicroscopy structure of four-stranded mini microtubules formed by bacterial tubulin-like Prosthecobacter dejongeii BtubAB proteins. Despite their much smaller diameter, mini microtubules share many key structural features with eukaryotic microtubules, such as an M-loop, alternating subunits, and a seam that breaks overall helical symmetry. Using in vitro total internal reflection fluorescence microscopy, we show that bacterial mini microtubules treadmill and display dynamic instability, another hallmark of eukaryotic microtubules. The third protein in the btub gene cluster, BtubC, previously known as "bacterial kinesin light chain," binds along protofilaments every 8 nm, inhibits BtubAB mini microtubule catastrophe, and increases rescue. Our work reveals that some bacteria contain regulated and dynamic cytomotive microtubule systems that were once thought to be only useful in much larger and sophisticated eukaryotic cells.

Methyl group conformation and hydrogen bonds in proteins determined by neutron protein crystallography

NASA Astrophysics Data System (ADS)

Yamaguchi, Atsushi; Shibata, Kouji; Tanaka, Ichiro; Niimura, Nobuo

2009-02-01

Using 'Hydrogen and Hydration in Proteins Data Base' (HHDB) that catalogs all H atom positions in biological macromolecules and in hydration water molecules that have been determined thus far by neutron macromolecular crystallography, methyl group conformation and hydrogen bonds (H.B.) in proteins are explored. It is found that most of the methyl groups belong to the stable staggered conformation but 11% of them seemed to be close to the eclipsed conformation. And geometrical consideration has been done for H.B. involved in α-helices. 125 H.B. were identified as donors for acceptor C dbnd O in the main chain α-helix. For these H.B., it is found that co-linear H.B. were rare, that hydrogen atoms seen from acceptors C dbnd O can localize upon certain arrangements, that H.B. are not parallel to the helix axis but rather inclined to C-terminal direction, and that hydrogen atoms except water are located inside, not outside of cylinders which the backbones of α-helices form.

Bottlebrush-Guided Polymer Crystallization Resulting in Supersoft and Reversibly Moldable Physical Networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daniel, William F. M.; Xie, Guojun; Vatankhah Varnoosfaderani, Mohammad

The goal of this study is to use ABA triblock copolymers with central bottlebrush B segments and crystalline linear chain A segments to demonstrate the effect of side chains on the formation and mechanical properties of physical networks cross-linked by crystallites. For this purpose, a series of bottlebrush copolymers was synthesized consisting of central amorphous bottlebrush polymer segments with a varying degree of polymerization (DP) of poly(n-butyl acrylate) (PnBA) side chains and linear tail blocks of crystallizable poly(octadecyl acrylate-stat-docosyl acrylate) (poly(ODA-stat-DA)). The materials were generated by sequential atom transfer radical polymerization (ATRP) steps starting with a series of bifunctional macroinitiatorsmore » followed by the growth of two ODA-stat-DA linear-chain tails and eventually growing poly(nBA) side chains with increasing DPs. Crystallization of the poly(ODA-stat-DA) tails resulted in a series of reversible physical networks with bottlebrush strands bridging crystalline cross-links. They displayed very low moduli of elasticity of the order of 10 3–10 4 Pa. These distinct properties are due to the bottlebrush architecture, wherein densely grafted side chains play a dual role by facilitating disentanglement of the network strands and confining crystallization of the linear-chain tails. This combination leads to physical cross-linking of supersoft networks without percolation of the crystalline phase. The cross-link density was effectively controlled by the DP of the side chains with respect to the DP of the linear tails (n A). Furthermore, shorter side chains allowed for crystallization of the linear tails of neighboring bottlebrushes, while steric repulsion between longer side chains hindered the phase separation and crystallization process and prevented network formation.« less

Bottlebrush-Guided Polymer Crystallization Resulting in Supersoft and Reversibly Moldable Physical Networks

DOE PAGES

Daniel, William F. M.; Xie, Guojun; Vatankhah Varnoosfaderani, Mohammad; ...

2017-02-24

The goal of this study is to use ABA triblock copolymers with central bottlebrush B segments and crystalline linear chain A segments to demonstrate the effect of side chains on the formation and mechanical properties of physical networks cross-linked by crystallites. For this purpose, a series of bottlebrush copolymers was synthesized consisting of central amorphous bottlebrush polymer segments with a varying degree of polymerization (DP) of poly(n-butyl acrylate) (PnBA) side chains and linear tail blocks of crystallizable poly(octadecyl acrylate-stat-docosyl acrylate) (poly(ODA-stat-DA)). The materials were generated by sequential atom transfer radical polymerization (ATRP) steps starting with a series of bifunctional macroinitiatorsmore » followed by the growth of two ODA-stat-DA linear-chain tails and eventually growing poly(nBA) side chains with increasing DPs. Crystallization of the poly(ODA-stat-DA) tails resulted in a series of reversible physical networks with bottlebrush strands bridging crystalline cross-links. They displayed very low moduli of elasticity of the order of 10 3–10 4 Pa. These distinct properties are due to the bottlebrush architecture, wherein densely grafted side chains play a dual role by facilitating disentanglement of the network strands and confining crystallization of the linear-chain tails. This combination leads to physical cross-linking of supersoft networks without percolation of the crystalline phase. The cross-link density was effectively controlled by the DP of the side chains with respect to the DP of the linear tails (n A). Furthermore, shorter side chains allowed for crystallization of the linear tails of neighboring bottlebrushes, while steric repulsion between longer side chains hindered the phase separation and crystallization process and prevented network formation.« less

26 CFR 1.472-8 - Dollar-value method of pricing LIFO inventories.

Code of Federal Regulations, 2014 CFR

2014-04-01

... “link-chain” method will be approved for taxable years beginning after December 31, 1960, only in those... nature of the pool. A taxpayer using either an index or link-chain method shall attach to his income tax return for the first taxable year beginning after December 31, 1960, for which the index or link-chain...

26 CFR 1.472-8 - Dollar-value method of pricing LIFO inventories.

Code of Federal Regulations, 2013 CFR

2013-04-01

... “link-chain” method will be approved for taxable years beginning after December 31, 1960, only in those... nature of the pool. A taxpayer using either an index or link-chain method shall attach to his income tax return for the first taxable year beginning after December 31, 1960, for which the index or link-chain...

26 CFR 1.472-8 - Dollar-value method of pricing LIFO inventories.

Code of Federal Regulations, 2011 CFR

2011-04-01

... “link-chain” method will be approved for taxable years beginning after December 31, 1960, only in those... nature of the pool. A taxpayer using either an index or link-chain method shall attach to his income tax return for the first taxable year beginning after December 31, 1960, for which the index or link-chain...

26 CFR 1.472-8 - Dollar-value method of pricing LIFO inventories.

Code of Federal Regulations, 2010 CFR

2010-04-01

... “link-chain” method will be approved for taxable years beginning after December 31, 1960, only in those... nature of the pool. A taxpayer using either an index or link-chain method shall attach to his income tax return for the first taxable year beginning after December 31, 1960, for which the index or link-chain...

26 CFR 1.472-8 - Dollar-value method of pricing LIFO inventories.

Code of Federal Regulations, 2012 CFR

2012-04-01

... “link-chain” method will be approved for taxable years beginning after December 31, 1960, only in those... nature of the pool. A taxpayer using either an index or link-chain method shall attach to his income tax return for the first taxable year beginning after December 31, 1960, for which the index or link-chain...

Central catalytic domain of BRAP (RNF52) recognizes the types of ubiquitin chains and utilizes oligo-ubiquitin for ubiquitylation.

PubMed

Shoji, Shisako; Hanada, Kazuharu; Ohsawa, Noboru; Shirouzu, Mikako

2017-09-07

Really interesting new gene (RING)-finger protein 52 (RNF52), an E3 ubiquitin ligase, is found in eukaryotes from yeast to humans. Human RNF52 is known as breast cancer type 1 susceptibility protein (BRCA1)-associated protein 2 (BRAP or BRAP2). The central catalytic domain of BRAP comprises four subdomains: nucleotide-binding α/β plait (NBP), really interesting new gene (RING) zinc finger, ubiquitin-specific protease (UBP)-like zinc finger (ZfUBP), and coiled-coil (CC). This domain architecture is conserved in RNF52 orthologs; however, the domain's function in the ubiquitin system has not been delineated. In the present study, we discovered that the RNF52 domain, comprising NBP-RING-ZfUBP-CC, binds to ubiquitin chains (oligo-ubiquitin) but not to the ubiquitin monomers, and can utilize various ubiquitin chains for ubiquitylation and auto-ubiquitylation. The RNF52 domain preferentially bound to M1- and K63-linked di-ubiquitin chains, weakly to K27-linked chains, but not to K6-, K11-, or K48-linked chains. The binding preferences of the RNF52 domain for ubiquitin-linkage types corresponded to ubiquitin usage in the ubiquitylation reaction, except for K11-, K29-, and K33-linked chains. Additionally, the RNF52 domain directly ligated the intact M1-linked, tri-, and tetra-ubiquitin chains and recognized the structural alterations caused by the phosphomimetic mutation of these ubiquitin chains. Full-length BRAP had nearly the same specificity for the ubiquitin-chain types as the RNF52 domain alone. Mass spectrometry analysis of oligomeric ubiquitylation products, mediated by the RNF52 domain, revealed that the ubiquitin-linkage types and auto-ubiquitylation sites depend on the length of ubiquitin chains. Here, we propose a model for the oligomeric ubiquitylation process, controlled by the RNF52 domain, which is not a sequential assembly process involving monomers. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Dynamics of structures in active suspensions of paramagnetic particles and applications to artificial micro-swimmers

NASA Astrophysics Data System (ADS)

Keaveny, Eric Edward

Micron-size paramagnetic particles suspended in viscous fluid will aggregate to form linear chains when subject to a uniform magnetic field. This process provides a way of changing the rheological properties of a suspension or building structures for microfluidic devices. We present a method to efficiently and accurately quantify the magnetic interactions between these particles. With this model and the force-coupling method, we perform simulations of both small ensembles and suspensions of thousands of paramagnetic particles subject to shear flows or rotating applied magnetic fields and demonstrate that in these situations an accurate representation of the fluid forces is necessary to estimate chain length. The artificial micro-swimmer is a device constructed from a flagellum-like tail of chemically linked paramagnetic beads tethered to a human red blood cell. To simulate this device, we develop an elastic coupling model that treats each chemical link as an inextensible, flexible rod. We demonstrate that when this device is subject to a rotating applied magnetic field, the filament tail will deform into a helical shape rotating with the field and propel the swimmer through the viscous fluid. Using a continuous elastica/resistive force model, we explore further the dependence of the swimming speed on the magnetic forces and swimmer geometry in the low frequency limit. We then examine the interactions between two comoving swimmers and ascertain at what separation distance a far-field approximation of the hydrodynamics is sufficient to reproduce the swimmers' dynamics. We also provide simulations of a single swimmer near a rigid surface and demonstrate that under certain conditions the presence of a wall can enhance the swimming speed. We determine further the height dependence of the repulsion from the surface, and, in the case of the spiral swimmer, the lateral drift speed. Finally, we consider a "squirmer" model for a swimming microorganism, appropriate for ciliary propulsion on time-scales much larger than the period of ciliary beating. We show that the "squirmer" model within the force-coupling method framework provides an effective simulation tool for studying low volume fraction suspensions of microorganisms.

Design of ferrocene-dipeptide bioorganometallic conjugates to induce chirality-organized structures.

PubMed

Moriuchi, Toshiyuki; Hirao, Toshikazu

2010-07-20

The highly ordered molecular assemblies in proteins can have a variety of functions, as observed in enzymes, receptors, and the like. Synthetic scientists are constructing bioinspired systems by harnessing the self-assembling properties of short peptides. Secondary structures such as alpha-helices, beta-sheets, and beta-turns are important in protein folding, which is mostly directed and stabilized by hydrogen bonding and the hydrophobic interactions of side chains. The design of secondary structure mimics that are composed of short peptides has attracted much attention, both for gaining fundamental insight into the factors affecting protein folding and for developing pharmacologically useful compounds, artificial receptors, asymmetric catalysts, and new materials. Ferrocenes are an organometallic scaffold with a central reverse-turn unit based on the inter-ring spacing of about 3.3 A, which is a suitable distance for hydrogen bonding between attached peptide strands. The conjugation of organometallic compounds with biomolecules such as amino acids, peptides, and DNA should provide novel systems that reflect properties of both the ferrocene and the biologically derived moieties. In this Account, we focus on recent advances in the design of ferrocene-peptide bioconjugates, which help illustrate the peptidomimetic basis for protein folding and the means of constructing highly ordered molecular assemblies. Ferrocene-peptide bioconjugates are constructed to form chirality-organized structures in both solid and solution states. The ferrocene serves as a reliable organometallic scaffold for the construction of protein secondary structures via intramolecular hydrogen bonding: the attached dipeptide strands are constrained within the appropriate dimensions. The introduction of the chiral dipeptide chains into the ferrocene scaffold induces the conformational enantiomerization of the ferrocenyl moiety; the chirality-organized structure results from intramolecular hydrogen bonding. The configuration and sequence of the amino acids are instrumental in the process. Regulation of the directionality and specificity of hydrogen bonding is a key component in the design of various molecular assemblies. Ferrocene-peptide bioconjugates also have a strong tendency to self-assemble through the contributions of available hydrogen-bonding donors in the solid state. Some ferrocene-peptide bioconjugates bearing only one dipeptide chain exhibit a helically ordered molecular assembly through a network of intermolecular (rather than intramolecular) hydrogen bonds. The propensity to form the chiral helicity appears to be controlled by the chirality of the dipeptide chains. Organization of host molecules is a useful strategy for forming artificial receptors. The conformationally regulated ferrocene-peptide bioconjugate provides the chirality-organized binding site for size-selective and chiral recognition of dicarboxylic acids through multipoint hydrogen bonds. Metal ions serve a variety of purposes in proteins, including structural stabilization for biological function. The complexation of ferrocene-peptide bioconjugates with palladium(II) compounds not only stabilizes the chirality conformational regulation but also induces conformational regulation of the dipeptide chain through complexation and intramolecular chirality organization. Construction of the chirality-organized ferrocene-peptide bioconjugates is also achieved by metal-directed assembly. These varied examples amply demonstrate the value of ferrocene-peptide bioconjugates in asserting architectural control over highly ordered molecular assemblies.

Finite size effect on hydrogen bond cooperativity in (Ala)n polypeptides: A DFT study using numeric atom-centered orbitals

NASA Astrophysics Data System (ADS)

Blum, Volker; Ireta, Joel; Scheffler, Matthias

2007-03-01

An accurate representation of the energetic contribution Ehb of hydrogen bonds to structure formation is paramount to understand the secondary structure stability of proteins, both qualitatively and quantitatively. However, Ehb depends strongly on its environment, and even on the surrounding peptide conformation itself. For instance, a short α-helical polypeptide (Ala)4 can not be stabilized by its single hydrogen bond, whereas an infinite α-helical chain (Ala)∞ is clearly energetically stable over a fully extended conformation. We here use all-electron density functional calculations in the PBE generalized gradient approximation by a recently developed, computationally efficient numeric atom-centered orbital based code^1 to investigate this H-bond cooperativity that is intrinsic to Alanine-based polypeptides (Ala)n (n=1-20,∞). We compare finite and infinite prototypical helical conformations (α, π, 310) on equal footing, with both neutral and ionic termination for finite (Ala)n peptides. Moderately sized NAO basis sets allow to capture Ehb with meV accuracy, revealing a clear jump in Ehb (cooperativity) when two H-bonds first appear in line, followed by slower and more continuous increase of Ehb towards n->∞. ^1 V. Blum, R. Gehrke, P. Havu, V. Havu, M. Scheffler, The FHI Ab Initio Molecular Simulations (aims) Project, Fritz-Haber-Institut, Berlin (2006).

A Rigidity-Enhanced Antimicrobial Activity: A Case for Linear Cationic α-Helical Peptide HP(2–20) and Its Four Analogues

PubMed Central

Liu, Li; Fang, Ying; Huang, Qingsheng; Wu, Jianhua

2011-01-01

Linear cationic α-helical antimicrobial peptides are referred to as one of the most likely substitutes for common antibiotics, due to their relatively simple structures (≤40 residues) and various antimicrobial activities against a wide range of pathogens. Of those, HP(2–20) was isolated from Helicobacter pylori ribosomal protein. To reveal a mechanical determinant that may mediate the antimicrobial activities, we examined the mechanical properties and structural stabilities of HP(2–20) and its four analogues of same chain length by steered molecular dynamics simulation. The results indicated the following: the resistance of H-bonds to the tensile extension mediated the early extensive stage; with the loss of H-bonds, the tensile force was dispensed to prompt the conformational phase transition; and Young's moduli (N/m2) of the peptides were about 4∼8×109. These mechanical features were sensitive to the variation of the residue compositions. Furthermore, we found that the antimicrobial activity is rigidity-enhanced, that is, a harder peptide has stronger antimicrobial activity. It suggests that the molecular spring constant may be used to seek a new structure-activity relationship for different α-helical peptide groups. This exciting result was reasonably explained by a possible mechanical mechanism that regulates both the membrane pore formation and the peptide insertion. PMID:21283643

Conservative mutation Met8 --> Leu affects the folding process and structural stability of squash trypsin inhibitor CMTI-I.

PubMed Central

Zhukov, I.; Jaroszewski, L.; Bierzyński, A.

2000-01-01

Protein molecules can accommodate a large number of mutations without noticeable effects on their stability and folding kinetics. On the other hand, some mutations can have quite strong effects on protein conformational properties. Such mutations either destabilize secondary structures, e.g., alpha-helices, are incompatible with close packing of protein hydrophobic cores, or lead to disruption of some specific interactions such as disulfide cross links, salt bridges, hydrogen bonds, or aromatic-aromatic contacts. The Met8 --> Leu mutation in CMTI-I results in significant destabilization of the protein structure. This effect could hardly be expected since the mutation is highly conservative, and the side chain of residue 8 is situated on the protein surface. We show that the protein destabilization is caused by rearrangement of a hydrophobic cluster formed by side chains of residues 8, Ile6, and Leu17 that leads to partial breaking of a hydrogen bond formed by the amide group of Leu17 with water and to a reduction of a hydrophobic surface buried within the cluster. The mutation perturbs also the protein folding. In aerobic conditions the reduced wild-type protein folds effectively into its native structure, whereas more then 75% of the mutant molecules are trapped in various misfolded species. The main conclusion of this work is that conservative mutations of hydrophobic residues can destabilize a protein structure even if these residues are situated on the protein surface and partially accessible to water. Structural rearrangement of small hydrophobic clusters formed by such residues can lead to local changes in protein hydration, and consequently, can affect considerably protein stability and folding process. PMID:10716179

A new model for the surface arrangement of myosin molecules in tarantula thick filaments.

PubMed

Offer, G; Knight, P J; Burgess, S A; Alamo, L; Padrón, R

2000-04-28

Three-dimensional reconstructions of the negatively stained thick filaments of tarantula muscle with a resolution of 50 A have previously suggested that the helical tracks of myosin heads are zigzagged, short diagonal ridges being connected by nearly axial links. However, surface views of lower contour levels reveal an additional J-shaped feature approximately the size and shape of a myosin head. We have modelled the surface array of myosin heads on the filaments using as a building block a model of a two-headed regulated myosin molecule in which the regulatory light chains of the two heads together form a compact head-tail junction. Four parameters defining the radius, orientation and rotation of each myosin molecule were varied. In addition, the heads were allowed independently to bend in a plane perpendicular to the coiled-coil tail at three sites, and to tilt with respect to the tail and to twist at one of these sites. After low-pass filtering, models were aligned with the reconstruction, scored by cross-correlation and refined by simulated annealing. Comparison of the geometry of the reconstruction and the distance between domains in the myosin molecule narrowed the choice of models to two main classes. A good match to the reconstruction was obtained with a model in which each ridge is formed from the motor domain of a head pointing to the bare zone together with the head-tail junction of a neighbouring molecule. The heads pointing to the Z-disc intermittently occupy the J-position. Each motor domain interacts with the essential and regulatory light chains of the neighbouring heads. A near-radial spoke in the reconstruction connecting the backbone to one end of the ridge can be identified as the start of the coiled-coil tail. Copyright 2000 Academic Press.

Fracture and damage evolution of fluorinated polymers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, E. N.; Rae, P.; Orler, E. B.

2004-01-01

Fluoropolymers are often semi-crystalline in nature, with their linear chains forming complicated phases near room temperature and ambient pressure. The most widely used fluorocarbon polymer for engineering applications is polytetrafluoroethylene (PTFE), due to its extremely low coefficient of friction, outstanding resistance to corrosion, and excellent electrical properties. The phase structure of PTFE is complex with four well-characterized crystalline phases (three observed at atmospheric pressure) and substantial molecular motion well below the melting point. The first-order transition at 19 C between phases II and IV is an unraveling in the helical conformation. Further rotational disordering and untwisting of the helices occursmore » above 30 C giving way to phase I. The mechanical behavior, including fracture and damage evolution, of PTFE depends on the chain and segment motions dictated by crystalline phase microstructure. The presence of three unique phases at ambient pressure near room temperature implies that failure during standard operating conditions may be strongly dependent on the phase. This paper presents a preliminary study of fracture and damage evolution in PTFE with the effects of temperature-induced phase on fracture mechanisms. The quasi-static fracture of PTFE in the atmospheric pressure regime, over a range of temperatures, was found to be strongly phase dependent: phase II exhibits brittle-fracture, phase IV displays ductile-fracture with crazing and some stable crack growth, and plastic flow dominates phase 1. The bulk failure properties are correlated to failure mechanisms through fractography of the fracture surfaces (optical microscopy and scanning electron microscopy (SEM)).« less

Metal binding characterization and conformational studies using Raman microscopy of resin-bound poly(aspartic acid).

PubMed

Stair, Jacqueline L; Holcombe, James A

2007-03-01

The metal binding capacities, conditional stability constants, and secondary structure of immobilized polyaspartic acid (PLAsp) (n = 6, 20, and 30) on TentaGel resin were determined when binding Mg2+, Co2+, Cd2+, and Ni2+. Metal binding to the synthesized peptides was evaluated using breakthrough curves from a packed microcolumn and flame atomic absorption spectrophotometry (FAAS) detection. The metal capacities reached values of 590, 2160, and 3710 mumol of metal/g of resin for the 6-mer, 20-mer, and 30-mer, respectively, and this resulted in 2-3 residues per metal for all peptides and metals tested. Surprisingly, the concentrated environment of the resin along with the spatial distribution of attachment groups allowed for most residues to participate in metal binding regardless of the peptide length. Conditional stability constants calculated using single metal binding isotherms indicated that binding strength decreased as the chain length increased on the resin. Raman microscopy on single beads was used to determine PLAsp secondary structure, and all peptides were of a mixed conformation (i.e., beta-sheets, alpha-helices, random chain, etc.) during neutral conditioning and metal binding. Uniquely, the longer 20-mer and 30-mer peptides showed a distinct change from a mixed conformation to beta-sheets and alpha-helices during metal release with acid. This study confirms that metal release by longer immobilized peptides is often assisted by a conformational change, which easily spoils the binding cavity, while shorter peptides may release metal primarily by H+ displacement.

A metal-linked gapped zipper model is proposed for the 90 kDa heat shock protein-estrogen receptor interface.

PubMed

Schwartz, J A; Mizukami, H

1991-06-01

A novel arrangement is proposed for the association of the 90 kDa heat shock protein (hsp 90) dimer and the human estrogen receptor (hER) monomer. Secondary structure analyses of the hsp 90 molecule reveal the presence of a cysteine-containing, leucine-rich, heptad repeat, which we refer to as region C. Similar analyses on the hER, at its hormone binding domain (HBD), have indicated the presence of a central subdomain bordered by 2 alpha-helical flanking segments which also display the heptad substructure. Due to its predicted potential for conformational change (1) we refer to this central subdomain as the Helix Conversion Unit or HCU. It contains an HX5C peptide and shares significant homology with the metal-binding domain of a gag-encoded HIV-LAV protein (2). We predict that, by virtue of its presence in duplicate, region C may be capable of simultaneous leucine zipper-like pairing with the hER at its flanking helices, as well as the formation of a shared CCHC-box-type metal binding link with the same hER at the putative HCU which lies in between.

Disulfide Cross-linking of a Multidrug and Toxic Compound Extrusion Transporter Impacts Multidrug Efflux*

PubMed Central

Radchenko, Martha; Nie, Rongxin; Lu, Min

2016-01-01

Multidrug and toxic compound extrusion (MATE) transporters contribute to multidrug resistance by extruding different drugs across cell membranes. The MATE transporters alternate between their extracellular and intracellular facing conformations to propel drug export, but how these structural changes occur is unclear. Here we combine site-specific cross-linking and functional studies to probe the movement of transmembrane helices in NorM from Neiserria gonorrheae (NorM-NG), a MATE transporter with known extracellular facing structure. We generated an active, cysteine-less NorM-NG and conducted pairwise cysteine mutagenesis on this variant. We found that copper phenanthroline catalyzed disulfide bond formation within five cysteine pairs and increased the electrophoretic mobility of the corresponding mutants. Furthermore, copper phenanthroline abolished the activity of the five paired cysteine mutants, suggesting that these substituted amino acids come in spatial proximity during transport, and the proximity changes are functionally indispensable. Our data also implied that the substrate-binding transmembrane helices move up to 10 Å in NorM-NG during transport and afforded distance restraints for modeling the intracellular facing transporter, thereby casting new light on the underlying mechanism. PMID:26975373

A Trigger Residue for Transmembrane Signaling in the Escherichia coli Serine Chemoreceptor.

PubMed

Kitanovic, Smiljka; Ames, Peter; Parkinson, John S

2015-08-01

The transmembrane Tsr protein of Escherichia coli mediates chemotactic responses to environmental serine gradients. Serine binds to the periplasmic domain of the homodimeric Tsr molecule, promoting a small inward displacement of one transmembrane helix (TM2). TM2 piston displacements, in turn, modulate the structural stability of the Tsr-HAMP domain on the cytoplasmic side of the membrane to control the autophosphorylation activity of the signaling CheA kinase bound to the membrane-distal cytoplasmic tip of Tsr. A five-residue control cable segment connects TM2 to the AS1 helix of HAMP and transmits stimulus and sensory adaptation signals between them. To explore the possible role of control cable helicity in transmembrane signaling by Tsr, we characterized the signaling properties of mutant receptors with various control cable alterations. An all-alanine control cable shifted Tsr output toward the kinase-on state, whereas an all-glycine control cable prevented Tsr from reaching either a fully on or fully off output state. Restoration of the native isoleucine (I214) in these synthetic control cables largely alleviated their signaling defects. Single amino acid replacements at Tsr-I214 shifted output toward the kinase-off (L, N, H, and R) or kinase-on (A and G) states, whereas other control cable residues tolerated most amino acid replacements with little change in signaling behavior. These findings indicate that changes in control cable helicity might mediate transitions between the kinase-on and kinase-off states during transmembrane signaling by chemoreceptors. Moreover, the Tsr-I214 side chain plays a key role, possibly through interaction with the membrane interfacial environment, in triggering signaling changes in response to TM2 piston displacements. The Tsr protein of E. coli mediates chemotactic responses to environmental serine gradients. Stimulus signals from the Tsr periplasmic sensing domain reach its cytoplasmic kinase control domain through piston displacements of a membrane-spanning helix and an adjoining five-residue control cable segment. We characterized the signaling properties of Tsr variants to elucidate the transmembrane signaling role of the control cable, an element present in many microbial sensory proteins. Both the kinase-on and kinase-off output states of Tsr depended on control cable helicity, but only one residue, I214, was critical for triggering responses to attractant inputs. These findings suggest that signal transmission in Tsr involves modulation of control cable helicity through interaction of the I214 side chain with the cytoplasmic membrane. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A Trigger Residue for Transmembrane Signaling in the Escherichia coli Serine Chemoreceptor

PubMed Central

Kitanovic, Smiljka; Ames, Peter

2015-01-01

ABSTRACT The transmembrane Tsr protein of Escherichia coli mediates chemotactic responses to environmental serine gradients. Serine binds to the periplasmic domain of the homodimeric Tsr molecule, promoting a small inward displacement of one transmembrane helix (TM2). TM2 piston displacements, in turn, modulate the structural stability of the Tsr-HAMP domain on the cytoplasmic side of the membrane to control the autophosphorylation activity of the signaling CheA kinase bound to the membrane-distal cytoplasmic tip of Tsr. A five-residue control cable segment connects TM2 to the AS1 helix of HAMP and transmits stimulus and sensory adaptation signals between them. To explore the possible role of control cable helicity in transmembrane signaling by Tsr, we characterized the signaling properties of mutant receptors with various control cable alterations. An all-alanine control cable shifted Tsr output toward the kinase-on state, whereas an all-glycine control cable prevented Tsr from reaching either a fully on or fully off output state. Restoration of the native isoleucine (I214) in these synthetic control cables largely alleviated their signaling defects. Single amino acid replacements at Tsr-I214 shifted output toward the kinase-off (L, N, H, and R) or kinase-on (A and G) states, whereas other control cable residues tolerated most amino acid replacements with little change in signaling behavior. These findings indicate that changes in control cable helicity might mediate transitions between the kinase-on and kinase-off states during transmembrane signaling by chemoreceptors. Moreover, the Tsr-I214 side chain plays a key role, possibly through interaction with the membrane interfacial environment, in triggering signaling changes in response to TM2 piston displacements. IMPORTANCE The Tsr protein of E. coli mediates chemotactic responses to environmental serine gradients. Stimulus signals from the Tsr periplasmic sensing domain reach its cytoplasmic kinase control domain through piston displacements of a membrane-spanning helix and an adjoining five-residue control cable segment. We characterized the signaling properties of Tsr variants to elucidate the transmembrane signaling role of the control cable, an element present in many microbial sensory proteins. Both the kinase-on and kinase-off output states of Tsr depended on control cable helicity, but only one residue, I214, was critical for triggering responses to attractant inputs. These findings suggest that signal transmission in Tsr involves modulation of control cable helicity through interaction of the I214 side chain with the cytoplasmic membrane. PMID:26013490

The NMR solution structure of a mutant of the Max b/HLH/LZ free of DNA: insights into the specific and reversible DNA binding mechanism of dimeric transcription factors.

PubMed

Sauvé, Simon; Tremblay, Luc; Lavigne, Pierre

2004-09-17

Basic region-helix1-loop-helix2-leucine zipper (b/H(1)LH(2)/LZ) transcription factors bind specific DNA sequence in their target gene promoters as dimers. Max, a b/H(1)LH(2)/LZ transcription factor, is the obligate heterodimeric partner of the related b/H(1)LH(2)/LZ proteins of the Myc and Mad families. These heterodimers specifically bind E-box DNA sequence (CACGTG) to activate (e.g. c-Myc/Max) and repress (e.g. Mad1/Max) transcription. Max can also homodimerize and bind E-box sequences in c-Myc target gene promoters. While the X-ray structure of the Max b/H(1)LH(2)/LZ/DNA complex and that of others have been reported, the precise sequence of events leading to the reversible and specific binding of these important transcription factors is still largely unknown. In order to provide insights into the DNA binding mechanism, we have solved the NMR solution structure of a covalently homodimerized version of a Max b/H(1)LH(2)/LZ protein with two stabilizing mutations in the LZ, and characterized its backbone dynamics from (15)N spin-relaxation measurements in the absence of DNA. Apart from minor differences in the pitch of the LZ, possibly resulting from the mutations in the construct, we observe that the packing of the helices in the H(1)LH(2) domain is almost identical to that of the two crystal structures, indicating that no important conformational change in these helices occurs upon DNA binding. Conversely to the crystal structures of the DNA complexes, the first 14 residues of the basic region are found to be mostly unfolded while the loop is observed to be flexible. This indicates that these domains undergo conformational changes upon DNA binding. On the other hand, we find the last four residues of the basic region form a persistent helical turn contiguous to H(1). In addition, we provide evidence of the existence of internal motions in the backbone of H(1) that are of larger amplitude and longer time-scale (nanoseconds) than the ones in the H(2) and LZ domain. Most interestingly, we note that conformers in the ensemble of calculated structures have highly conserved basic residues (located in the persistent helical turn of the basic region and in the loop) known to be important for specific binding in a conformation that matches that of the DNA-bound state. These partially prefolded conformers can directly fit into the major groove of DNA and as such are proposed to lie on the pathway leading to the reversible and specific DNA binding. In these conformers, the conserved basic side-chains form a cluster that elevates the local electrostatic potential and could provide the necessary driving force for the generation of the internal motions localized in the H(1) and therefore link structural determinants with the DNA binding function. Overall, our results suggests that the Max homodimeric b/H(1)LH(2)/LZ can rapidly and preferentially bind DNA sequence through transient and partially prefolded states and subsequently, adopt the fully helical bound state in a DNA-assisted mechanism or induced-fit.

Crystal structure of allyl­ammonium hydrogen succinate at 100 K

PubMed Central

Dziuk, Błażej; Zarychta, Bartosz; Ejsmont, Krzysztof

2014-01-01

The asymmetric unit of the title compound, C2H8N+·C4H5O4 −, consists of two allyl­ammonium cations and two hydrogen succinate anions (Z′ = 2). One of the cations has a near-perfect syn-periplanar (cis) conformation with an N—C—C—C torsion angle of 0.4 (3)°, while the other is characterized by a gauche conformation and a torsion angle of 102.5 (3)°. Regarding the anions, three out of four carboxilic groups are twisted with respect to the central C–CH2–CH2–C group [dihedral angles = 24.4 (2), 31.2 (2) and 40.4 (2)°], the remaining one being instead almost coplanar, with a dihedral angle of 4.0 (2)°. In the crystal, there are two very short, near linear O—H⋯O hydrogen bonds between anions, with the H atoms shifted notably from the donor O towards the O⋯O midpoint. These O—H⋯O hydrogen bonds form helical chains along the [011] which are further linked to each other through N—H⋯O hydrogen bonds (involving all the available NH groups), forming layers lying parallel to (100). PMID:25309251

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rushton, Phillip S.; Olek, Anna T.; Makowski, Lee

The crystallographic structure of a rice (Oryza sativa) cellulose synthase, OsCesA8, plant-conserved region (P-CR), one of two unique domains in the catalytic domain of plant CesAs, was solved to 2.4 Å resolution. Two antiparallel α-helices form a coiled-coil domain linked by a large extended connector loop containing a conserved trio of aromatic residues. The P-CR structure was fit into a molecular envelope for the P-CR domain derived from small-angle X-ray scattering data. The P-CR structure and molecular envelope, combined with a homology-based chain trace of the CesA8 catalytic core, were modeled into a previously determined CesA8 small-angle X-ray scattering molecularmore » envelope to produce a detailed topological model of the CesA8 catalytic domain. The predicted position for the P-CR domain from the molecular docking models places the P-CR connector loop into a hydrophobic pocket of the catalytic core, with the coiled-coil aligned near the entrance of the substrate UDP-glucose into the active site. In this configuration, the P-CR coiled-coil alone is unlikely to regulate substrate access to the active site, but it could interact with other domains of CesA, accessory proteins, or other CesA catalytic domains to control substrate delivery.« less

Solution NMR and molecular dynamics reveal a persistent alpha helix within the dynamic region of PsbQ from photosystem II of higher plants.

PubMed

Rathner, Petr; Rathner, Adriana; Horničáková, Michaela; Wohlschlager, Christian; Chandra, Kousik; Kohoutová, Jaroslava; Ettrich, Rüdiger; Wimmer, Reinhard; Müller, Norbert

2015-09-01

The extrinsic proteins of photosystem II of higher plants and green algae PsbO, PsbP, PsbQ, and PsbR are essential for stable oxygen production in the oxygen evolving center. In the available X-ray crystallographic structure of higher plant PsbQ residues S14-Y33 are missing. Building on the backbone NMR assignment of PsbQ, which includes this "missing link", we report the extended resonance assignment including side chain atoms. Based on nuclear Overhauser effect spectra a high resolution solution structure of PsbQ with a backbone RMSD of 0.81 Å was obtained from torsion angle dynamics. Within the N-terminal residues 1-45 the solution structure deviates significantly from the X-ray crystallographic one, while the four-helix bundle core found previously is confirmed. A short α-helix is observed in the solution structure at the location where a β-strand had been proposed in the earlier crystallographic study. NMR relaxation data and unrestrained molecular dynamics simulations corroborate that the N-terminal region behaves as a flexible tail with a persistent short local helical secondary structure, while no indications of forming a β-strand are found. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

A folding-dependent mechanism of antimicrobial peptide resistance to degradation unveiled by solution structure of distinctin

PubMed Central

Raimondo, Domenico; Andreotti, Giuseppina; Saint, Nathalie; Amodeo, Pietro; Renzone, Giovanni; Sanseverino, Marina; Zocchi, Ivana; Molle, Gerard; Motta, Andrea; Scaloni, Andrea

2005-01-01

Many bioactive peptides, presenting an unstructured conformation in aqueous solution, are made resistant to degradation by posttranslational modifications. Here, we describe how molecular oligomerization in aqueous solution can generate a still unknown transport form for amphipathic peptides, which is more compact and resistant to proteases than forms related to any possible monomer. This phenomenon emerged from 3D structure, function, and degradation properties of distinctin, a heterodimeric antimicrobial compound consisting of two peptide chains linked by a disulfide bond. After homodimerization in water, this peptide exhibited a fold consisting of a symmetrical full-parallel four-helix bundle, with a well secluded hydrophobic core and exposed basic residues. This fold significantly stabilizes distinctin against proteases compared with other linear amphipathic peptides, without affecting its antimicrobial, hemolytic, and ion-channel formation properties after membrane interaction. This full-parallel helical orientation represents a perfect compromise between formation of a stable structure in water and requirement of a drastic structural rearrangement in membranes to elicit antimicrobial potential. Thus, distinctin can be claimed as a prototype of a previously unrecognized class of antimicrobial derivatives. These results suggest a critical revision of the role of peptide oligomerization whenever solubility or resistance to proteases is known to affect biological properties. PMID:15840728

Synthesis, structural characterization and luminescence properties of 1-carboxymethyl-3-ethylimidazolium chloride

DOE PAGES

Prodius, Denis; Wilk-Kozubek, Magdalena; Mudring, Anja -Verena

2018-05-08

A microcrystalline carboxyl-functionalized imidazolium chloride, namely 1-carboxymethyl-3-ethylimidazolium chloride, C 7H 11N 2O 2 +·Cl –, has been synthesized and characterized by elemental analysis, attenuated total reflectance Fourier transform IR spectroscopy (ATR-FT-IR), single-crystal X-ray diffraction, thermal analysis (TGA/DSC), and photoluminescence spectroscopy. In the crystal structure, cations and anions are linked by C—H...Cl and C—H...O hydrogen bonds to create a helix along the [010] direction. Adjacent helical chains are further interconnected through O—H...Cl and C—H...O hydrogen bonds to form a (101¯) layer. Finally, neighboring layers are joined together via C—H...Cl contacts to generate a three-dimensional supramolecular architecture. Thermal analyses reveal that themore » compound melts at 449.7 K and is stable up to 560.0 K under a dynamic air atmosphere. Photoluminescence measurements show that the compound exhibits a blue fluorescence and a green phosphorescence associated with spin-allowed ( 1π← 1π*) and spin-forbidden ( 1π← 3π*) transitions, respectively. As a result, the average luminescence lifetime was determined to be 1.40 ns for the short-lived ( 1π← 1π*) transition and 105 ms for the long-lived ( 1π← 3π*) transition.« less

Energy landscapes of the monomer and dimer of the Alzheimer's peptide A β (1 -28 )

NASA Astrophysics Data System (ADS)

Dong, Xiao; Chen, Wei; Mousseau, Normand; Derreumaux, Philippe

2008-03-01

The cytoxicity of Alzheimer's disease has been linked to the self-assembly of the 40 /42 amino acid of the amyloid-β (A β ) peptide into oligomers. To understand the assembly process, it is important to characterize the very first steps of aggregation at an atomic level of detail. Here, we focus on the N-terminal fragment 1-28, known to form fibrils in vitro. Circular dichroism and NMR experiments indicate that the monomer of A β (1 -28 ) is α -helical in a membranelike environment and random coil in aqueous solution. Using the activation-relaxation technique coupled with the OPEP coarse grained force field, we determine the structures of the monomer and of the dimer of A β (1 -28 ) . In agreement with experiments, we find that the monomer is predominantly random coil in character, but displays a non-negligible β -strand probability in the N-terminal region. Dimerization impacts the structure of each chain and leads to an ensemble of intertwined conformations with little β -strand content in the region Leu17-Ala21. All these structural characteristics are inconsistent with the amyloid fibril structure and indicate that the dimer has to undergo significant rearrangement en route to fibril formation.

Synthesis, structural characterization and luminescence properties of 1-carboxymethyl-3-ethylimidazolium chloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prodius, Denis; Wilk-Kozubek, Magdalena; Mudring, Anja -Verena

A microcrystalline carboxyl-functionalized imidazolium chloride, namely 1-carboxymethyl-3-ethylimidazolium chloride, C 7H 11N 2O 2 +·Cl –, has been synthesized and characterized by elemental analysis, attenuated total reflectance Fourier transform IR spectroscopy (ATR-FT-IR), single-crystal X-ray diffraction, thermal analysis (TGA/DSC), and photoluminescence spectroscopy. In the crystal structure, cations and anions are linked by C—H...Cl and C—H...O hydrogen bonds to create a helix along the [010] direction. Adjacent helical chains are further interconnected through O—H...Cl and C—H...O hydrogen bonds to form a (101¯) layer. Finally, neighboring layers are joined together via C—H...Cl contacts to generate a three-dimensional supramolecular architecture. Thermal analyses reveal that themore » compound melts at 449.7 K and is stable up to 560.0 K under a dynamic air atmosphere. Photoluminescence measurements show that the compound exhibits a blue fluorescence and a green phosphorescence associated with spin-allowed ( 1π← 1π*) and spin-forbidden ( 1π← 3π*) transitions, respectively. As a result, the average luminescence lifetime was determined to be 1.40 ns for the short-lived ( 1π← 1π*) transition and 105 ms for the long-lived ( 1π← 3π*) transition.« less

Mercury coordination polymers with flexible ethane-1,2-diyl-bis-(pyridyl-3-carboxylate): Synthesis, structures, thermal and luminescent properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vallejos, Javier; Brito, Iván, E-mail: ivanbritob@yahoo.com; Cárdenas, Alejandro

2015-03-15

The reaction of the flexible ligand, ethane-1,2-diyl-bis-(pyridyl-3-carboxylate), (L) with HgI{sub 2} and HgBr{sub 2} salts under the same experimental conditions leads to the formation of two coordination polymers with different motifs: ([Hg(L)(Br{sub 2})]){sub n}(1) and ([Hg(L)(I{sub 2})]){sub n}(2). In both compounds, the ligand, (L) acts in a μ2-N:N′-bidentate fashion to link HgBr{sub 2} and HgI{sub 2} units to form a linear and helical chain motif, along [1 0 0] for (1) and [0 0 1] for (2). The ethylene moiety of (L) has gauche and trans conformation in compounds (1) and (2), respectively. The flexible conformation of L produces differencesmore » in the optical and crystal properties of the two compounds. - Graphical abstract: This work demonstrates how the HgX{sub 2} units are coordinates by bi-dentate ligand forming polymeric coordination complexes by self-assembly of both chemical units.- Highlights: • News 1-D d{sup 10} transition metal coordination polymers. • The photoluminescent properties have been measured. • The thermal properties have been measured.« less

Linking matrices in systems with periodic boundary conditions

NASA Astrophysics Data System (ADS)

Panagiotou, Eleni; Millett, Kenneth C.

2018-06-01

We study the linking matrix, a measure of entanglement for a collection of closed or open chains in 3-space based on the Gauss linking number. Periodic boundary conditions (PBC) are often used in the simulation of physical systems of filaments. To measure entanglement of closed or open chains in systems employing PBC we use the periodic linking matrix, based on the periodic linking number, defined in Panagiotou (2015 J. Comput. Phys. 300 533–73). We study the properties of the periodic linking matrix as a function of cell size. We provide analytical results concerning the eigenvalues of the periodic linking matrix and show that some of them are invariant of cell-size.

Relationship between helix stability and binding affinities: molecular dynamics simulations of Bfl-1/A1-binding pro-apoptotic BH3 peptide helices in explicit solvent.

PubMed

Modi, Vivek; Lama, Dilraj; Sankararamakrishnan, Ramasubbu

2013-01-01

The anti-apoptotic protein Bfl-1, also known as A1, belongs to the Bcl-2 family of proteins and interacts with pro-apoptotic Bcl-2 counterparts to regulate programmed cell death. As demonstrated for other anti-apoptotic Bcl-2 proteins, Bfl-1/A1 has also been shown to be overexpressed in various human cancers and hence they are attractive targets for anticancer drugs. Peptides derived from the BH3 region of pro-apoptotic Bcl-2 proteins have been shown to elicit similar biological response as that of parent proteins. BH3 peptides from different pro-apoptotic proteins have wide range of affinities for Bfl-1/A1. Experimentally determined complex structures show that the hydrophobic side of amphipathic BH3 peptides binds to the hydrophobic groove formed by the α-helical bundle of Bfl-1/A1 protein. Apart from the length and amino acid composition, a BH3 peptide's ability to form a stable helical structure has been suggested to be important for its high binding affinity. Molecular dynamics simulations of three BH3 peptides derived from the pro-apoptotic proteins Bak, Bid, and Bmf were carried out each for a period of at least 100 ns after 2 ns equilibration run. The length of simulated BH3 peptides varied from 22 to 24 residues and their binding affinities for Bfl-1/A1 varied from 1 to 180 nM. Our results show that the hydrophobic residues from the hydrophobic face of BH3 peptides tend to cluster together quickly to avoid being exposed to the solvent. This resulted in either reduction of helix length or complete loss of helical character. Bak and Bid BH3 peptides with high affinities for Bf1-1/A1 have stable helical segments in the N-terminal region. The highly conserved Leu residue lies just outside the helical region at the C-terminal end. Capping interactions arising out of N-cap residues seem to be extremely important to maintain the helical stability. Favorable hydrophilic interactions between residues also give further stability to the helix fragment and at least one of the interacting residues resides within the helical region. Bmf BH3 peptide with a weaker binding affinity for Bmf-1/A1 completely lost its helical character at the end of 100 ns production run and a further 50 ns simulation showed that the Bmf peptide continues to remain in random conformation. The present study clearly establishes a link between a BH3 peptide's ability to form a stable helical segment and its high binding affinity for an anti-apoptotic protein. To further test this hypothesis, we simulated a mutant Bmf peptide for 100 ns in which two residues R129 and H146 were substituted by Asn in silico in the wild-type peptide. Introduction of N-terminal Asn clearly enabled the formation of capping interactions at the N-terminus and resulted in a stable N-terminal helical segment. This demonstrates that the knowledge of interactions that help to maintain stable helical segments in a high-affinity BH3 peptide will help in designing highly specific peptide-based drugs/inhibitors. Such molecules will have the ability to bind a particular anti-apoptotic protein with high affinity.

Three-dimensional scrape off layer transport in the helically symmetric experiment HSX

NASA Astrophysics Data System (ADS)

Akerson, A. R.; Bader, A.; Hegna, C. C.; Schmitz, O.; Stephey, L. A.; Anderson, D. T.; Anderson, F. S. B.; Likin, K. M.

2016-08-01

The edge topology of helically symmetric experiment (HSX) in the quasi-helically symmetric configuration is characterized by an 8/7 magnetic island remnant embedded in a short connection length scrape-off layer (SOL) domain. A 2D mapping of edge plasma profiles within this heterogeneous SOL has been constructed using a movable, multi-pin Langmuir probe. Comparisons of these measurements to edge simulations using the EMC3-EIRENE 3D plasma fluid and kinetic neutral gas transport model have been performed. The measurements provide strong evidence that particle transport is diffusive within the island region and dominantly convective in the SOL region. Measurements indicate that phenomenological cross-field diffusion coefficients are low in the SOL region between the last closed flux surface and edge island (i.e. {{D}\\bot}≈ 0.03 m2 s-1). This level of transport was found to increase by a factor of two when a limiter is inserted almost completely into the magnetic island. A reduction in gradients of the edge electrostatic plasma potential was also measured in this configuration, suggesting that the reduced electric field may be linked to the increased cross-field transport observed.

In Vitro MRV-based Hemodynamic Study of Complex Helical Flow in a Patient-specific Jugular Model

NASA Astrophysics Data System (ADS)

Kefayati, Sarah; Acevedo-Bolton, Gabriel; Haraldsson, Henrik; Saloner, David

2014-11-01

Neurointerventional Radiologists are frequently requested to evaluate the venous side of the intracranial circulation for a variety of conditions including: Chronic Cerebrospinal Venous Insufficiency thought to play a role in the development of multiple sclerosis; sigmoid sinus diverticulum which has been linked to the presence of pulsatile tinnitus; and jugular vein distension which is related to cardiac dysfunction. Most approaches to evaluating these conditions rely on structural assessment or two dimensional flow analyses. This study was designed to investigate the highly complex jugular flow conditions using magnetic resonance velocimetry (MRV). A jugular phantom was fabricated based on the geometry of the dominant jugular in a tinnitus patient. Volumetric three-component time-resolved velocity fields were obtained using 4D PC-MRI -with the protocol enabling turbulence acquisition- and the patient-specific pulsatile waveform. Flow was highly complex exhibiting regions of jet, high swirling strength, and strong helical pattern with the core originating from the focal point of the jugular bulb. Specifically, flow was analyzed for helicity and the level of turbulence kinetic energy elevated in the core of helix and distally, in the post-narrowing region.

Random single amino acid deletion sampling unveils structural tolerance and the benefits of helical registry shift on GFP folding and structure.

PubMed

Arpino, James A J; Reddington, Samuel C; Halliwell, Lisa M; Rizkallah, Pierre J; Jones, D Dafydd

2014-06-10

Altering a protein's backbone through amino acid deletion is a common evolutionary mutational mechanism, but is generally ignored during protein engineering primarily because its effect on the folding-structure-function relationship is difficult to predict. Using directed evolution, enhanced green fluorescent protein (EGFP) was observed to tolerate residue deletion across the breadth of the protein, particularly within short and long loops, helical elements, and at the termini of strands. A variant with G4 removed from a helix (EGFP(G4Δ)) conferred significantly higher cellular fluorescence. Folding analysis revealed that EGFP(G4Δ) retained more structure upon unfolding and refolded with almost 100% efficiency but at the expense of thermodynamic stability. The EGFP(G4Δ) structure revealed that G4 deletion caused a beneficial helical registry shift resulting in a new polar interaction network, which potentially stabilizes a cis proline peptide bond and links secondary structure elements. Thus, deletion mutations and registry shifts can enhance proteins through structural rearrangements not possible by substitution mutations alone. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

N-terminal aliphatic residues dictate the structure, stability, assembly, and small molecule binding of the coiled-coil region of cartilage oligomeric matrix protein.

PubMed

Gunasekar, Susheel K; Asnani, Mukta; Limbad, Chandani; Haghpanah, Jennifer S; Hom, Wendy; Barra, Hanna; Nanda, Soumya; Lu, Min; Montclare, Jin Kim

2009-09-15

The coiled-coil domain of cartilage oligomeric matrix protein (COMPcc) assembles into a homopentamer that naturally recognizes the small molecule 1,25-dihydroxyvitamin D(3) (vit D). To identify the residues critical for the structure, stability, oligomerization, and binding to vit D as well as two other small molecules, all-trans-retinol (ATR) and curcumin (CCM), here we perform an alanine scanning mutagenesis study. Ten residues lining the hydrophobic pocket of COMPcc were mutated into alanine; of the mutated residues, the N-terminal aliphatic residues L37, L44, V47, and L51 are responsible for maintaining the structure and function. Furthermore, two polar residues, T40 and Q54, within the N-terminal region when converted into alanine improve the alpha-helical structure, stability, and self-assembly behavior. Helical stability, oligomerization, and binding appear to be linked in a manner in which mutations that abolish helical structure and assembly bind poorly to vit D, ATR, and CCM. These results provide not only insight into COMPcc and its functional role but also useful guidelines for the design of stable, pentameric coiled-coils capable of selectively storing and delivering various small molecules.

The helical ventricular myocardial band: global, three-dimensional, functional architecture of the ventricular myocardium.

PubMed

Kocica, Mladen J; Corno, Antonio F; Carreras-Costa, Francesc; Ballester-Rodes, Manel; Moghbel, Mark C; Cueva, Clotario N C; Lackovic, Vesna; Kanjuh, Vladimir I; Torrent-Guasp, Francisco

2006-04-01

We are currently witnessing the advent of new diagnostic tools and therapies for heart diseases, but, without serious scientific consensus on fundamental questions about normal and diseased heart structure and function. During the last decade, three successive, international, multidisciplinary symposia were organized in order to setup fundamental research principles, which would allow us to make a significant step forward in understanding heart structure and function. Helical ventricular myocardial band of Torrent-Guasp is the revolutionary new concept in understanding global, three-dimensional, functional architecture of the ventricular myocardium. This concept defines the principal, cumulative vectors, integrating the tissue architecture (i.e. form) and net forces developed (i.e. function) within the ventricular mass. Here we expose the compendium of Torrent-Guasp's half-century long functional anatomical investigations in the light of ongoing efforts to define the integrative approach, which would lead to new understanding of the ventricular form and function by linking across multiple scales of biological organization, as defined in ongoing Physiome project. Helical ventricular myocardial band of Torrent-Guasp may also, hopefully, allow overcoming some difficulties encountered in contemporary efforts to create a comprehensive mathematical model of the heart.

Conditional solvation thermodynamics of isoleucine in model peptides and the limitations of the group-transfer model.

PubMed

Tomar, Dheeraj S; Weber, Valéry; Pettitt, B Montgomery; Asthagiri, D

2014-04-17

The hydration thermodynamics of the amino acid X relative to the reference G (glycine) or the hydration thermodynamics of a small-molecule analog of the side chain of X is often used to model the contribution of X to protein stability and solution thermodynamics. We consider the reasons for successes and limitations of this approach by calculating and comparing the conditional excess free energy, enthalpy, and entropy of hydration of the isoleucine side chain in zwitterionic isoleucine, in extended penta-peptides, and in helical deca-peptides. Butane in gauche conformation serves as a small-molecule analog for the isoleucine side chain. Parsing the hydrophobic and hydrophilic contributions to hydration for the side chain shows that both of these aspects of hydration are context-sensitive. Furthermore, analyzing the solute-solvent interaction contribution to the conditional excess enthalpy of the side chain shows that what is nominally considered a property of the side chain includes entirely nonobvious contributions of the background. The context-sensitivity of hydrophobic and hydrophilic hydration and the conflation of background contributions with energetics attributed to the side chain limit the ability of a single scaling factor, such as the fractional solvent exposure of the group in the protein, to map the component energetic contributions of the model-compound data to their value in the protein. But ignoring the origin of cancellations in the underlying components the group-transfer model may appear to provide a reasonable estimate of the free energy for a given error tolerance.

Multi angle laser light scattering evaluation of field exposed thermoplastic photovoltaic encapsulant materials

DOE PAGES

Kempe, Michael D.; Miller, David C.; Wohlgemuth, John H.; ...

2016-01-08

As creep of polymeric materials is potentially a safety concern for photovoltaic modules, the potential for module creep has become a significant topic of discussion in the development of IEC 61730 and IEC 61215. To investigate the possibility of creep, modules were constructed, using several thermoplastic encapsulant materials, into thin-film mock modules and deployed in Mesa, Arizona. The materials examined included poly(ethylene)-co-vinyl acetate (EVA, including formulations both cross-linked and with no curing agent), polyethylene/polyoctene copolymer (PO), poly(dimethylsiloxane) (PDMS), polyvinyl butyral (PVB), and thermoplastic polyurethane (TPU). The absence of creep in this experiment is attributable to several factors of which themore » most notable one was the unexpected cross-linking of an EVA formulation without a cross-linking agent. It was also found that some materials experienced both chain scission and cross-linking reactions, sometimes with a significant dependence on location within a module. The TPU and EVA samples were found to degrade with cross-linking reactions dominating over chain scission. In contrast, the PO materials degraded with chain scission dominating over cross-linking reactions. Furthermore, we found no significant indications that viscous creep is likely to occur in fielded modules capable of passing the qualification tests, we note that one should consider how a polymer degrades, chain scission or cross-linking, in assessing the suitability of a thermoplastic polymer in terrestrial photovoltaic applications.« less

Improved side-chain torsion potentials for the Amber ff99SB protein force field

PubMed Central

Lindorff-Larsen, Kresten; Piana, Stefano; Palmo, Kim; Maragakis, Paul; Klepeis, John L; Dror, Ron O; Shaw, David E

2010-01-01

Recent advances in hardware and software have enabled increasingly long molecular dynamics (MD) simulations of biomolecules, exposing certain limitations in the accuracy of the force fields used for such simulations and spurring efforts to refine these force fields. Recent modifications to the Amber and CHARMM protein force fields, for example, have improved the backbone torsion potentials, remedying deficiencies in earlier versions. Here, we further advance simulation accuracy by improving the amino acid side-chain torsion potentials of the Amber ff99SB force field. First, we used simulations of model alpha-helical systems to identify the four residue types whose rotamer distribution differed the most from expectations based on Protein Data Bank statistics. Second, we optimized the side-chain torsion potentials of these residues to match new, high-level quantum-mechanical calculations. Finally, we used microsecond-timescale MD simulations in explicit solvent to validate the resulting force field against a large set of experimental NMR measurements that directly probe side-chain conformations. The new force field, which we have termed Amber ff99SB-ILDN, exhibits considerably better agreement with the NMR data. Proteins 2010. © 2010 Wiley-Liss, Inc. PMID:20408171

The synthesis and structure of a chiral 1D aluminophosphate chain compound: d-Co(en) 3[AlP 2O 8]·6.5H 2O

NASA Astrophysics Data System (ADS)

Chen, Peng; Li, Jiyang; Yu, Jihong; Wang, Yu; Pan, Qinhe; Xu, Ruren

2005-06-01

A new chiral one-dimensional (1D) aluminophosphate chain compound [ d-Co(en) 3][AlP 2O 8]·6.5H 2O (designated AlPO-CJ22) has been hydrothermally synthesized by using the optically pure d-Co(en) 3I 3 complex as the template. Single-crystal structural analysis reveals that its structure is built up from alternating connection of AlO 4 and PO 2(=O 2) tetrahedra to form corner-shared Al 2P 2 four-membered ring (4-MR) chains. The d-Co(en) 33+ complex cations extended along the 2 1 screw axis interact with the inorganic chains through hydrogen-bonds of N⋯O atoms in a helical fashion. Optical rotation measurement shows that AlPO-CJ22 is chiral as with d-Co(en) 33+ complex cations. Crystal data: orthorhombic, I2 12 12 1, a=8.5573(8) Å, b=22.613(2) Å, c=22.605(2) Å, Z=8, R1=0.067, wR2=0.1291, and Flack parameter: -0.02(3). CCDC number: 254179.

Foreign Languages: Key Links in the Chain of Learning.

ERIC Educational Resources Information Center

Mead, Robert G., Jr., Ed.

The articles discuss the necessity of including foreign language as an integral part of the curriculum at all levels of instruction. The following chapters are included: "Elementary School Foreign Language: Key Link in the Chain of Learning" (rationale, innovations, immersion programs, and interdisciplinary approaches); "Foreign…

The role of living/controlled radical polymerization in the formation of improved imprinted polymers.

PubMed

Salian, Vishal D; Vaughan, Asa D; Byrne, Mark E

2012-06-01

In this work, living/controlled radical polymerization (LRP) is compared with conventional free radical polymerization in the creation of highly and weakly cross-linked imprinted poly(methacrylic acid-co-ethylene glycol dimethacrylate) networks. It elucidates, for the first time, the effect of LRP on the chain level and begins to explain why the efficiency of the imprinting process is improved using LRP. Imprinted polymers produced via LRP exhibited significantly higher template affinity and capacity compared with polymers prepared using conventional methods. The use of LRP in the creation of highly cross-linked imprinted polymers resulted in a fourfold increase in binding capacity without a decrease in affinity; whereas weakly cross-linked gels demonstrated a nearly threefold increase in binding capacity at equivalent affinity when LRP was used. In addition, by adjusting the double bond conversion, we can choose to increase either the capacity or the affinity in highly cross-linked imprinted polymers, thus allowing the creation of imprinted polymers with tailorable binding parameters. Using free radical polymerization in the creation of polymer chains, as the template-monomer ratio increased, the average molecular weight of the polymer chains decreased despite a slight increase in the double bond conversion. Thus, the polymer chains formed were shorter but greater in number. Using LRP neutralized the effect of the template. The addition of chain transfer agent resulted in slow, uniform, simultaneous chain growth, resulting in the formation of longer more monodisperse chains. Reaction analysis revealed that propagation time was extended threefold in the formation of highly cross-linked polymers when LRP techniques were used. This delayed the transition to the diffusion-controlled stage of the reaction, which in turn led to the observed enhanced binding properties, decreased polydispersity in the chains, and a more homogeneous macromolecular architecture. Copyright © 2012 John Wiley & Sons, Ltd.

catena-Poly[[[(2,2′-bipyridine-κ2 N,N′)cobalt(II)]-μ-(E)-3,3′-(but-2-ene-2,3-di­yl)dibenzoato-κ4 O,O′:O′′,O′′′] hemihydrate

PubMed Central

Li, Zong-Sheng; Ng, Seik Weng

2011-01-01

The title coordination polymer, {[Co(C18H14O4)(C10H8N2)]·0.5H2O}n, features a helical polymeric chain that runs along the b axis. The Co atoms are chelated by the carboxyl­ate groups of two 3,3′-(but-2-ene-2,3-di­yl)dibenzoate ligands and the N atoms of a 2,2′-bipyridine ligand. The lattice water mol­ecule is disordered about a center of inversion and is connected to the chain by an O—H⋯O hydrogen bond. The CoII atom shows a distorted octa­hedral coordination. PMID:22219789

Structure of chromatin and the linking number of DNA.

PubMed Central

Worcel, A; Strogatz, S; Riley, D

1981-01-01

Recent observations suggest that the basic supranucleosomal structure of chromatin is a zigzag helical ribbon with a repeat unit made of two nucleosomes connected by a relaxed spacer DNA. A remarkable feature of one particular ribbon is that it solves the apparent paradox between the number of DNA turns per nucleosome and the total linking number of a nucleosome-containing closed circular DNA molecule. We show here that the repeat unit of the proposed structure, which contains two nucleosomes with -1 3/4 DNA turns per nucleosome and one spacer crossover per repeat, contributes -2 to the linking number of closed circular DNA. Space-filling models show that the cylindrical 250-A chromatin fiber can be generated by twisting the ribbon. Images PMID:6940168

Secondary structure of spiralin in solution, at the air/water interface, and in interaction with lipid monolayers.

PubMed

Castano, Sabine; Blaudez, Daniel; Desbat, Bernard; Dufourcq, Jean; Wróblewski, Henri

2002-05-03

The surface of spiroplasmas, helically shaped pathogenic bacteria related to the mycoplasmas, is crowded with the membrane-anchored lipoprotein spiralin whose structure and function are unknown. In this work, the secondary structure of spiralin under the form of detergent-free micelles (average Stokes radius, 87.5 A) in water and at the air/water interface, alone or in interaction with lipid monolayers was analyzed. FT-IR and circular dichroism (CD) spectroscopic data indicate that spiralin in solution contains about 25+/-3% of helices and 38+/-2% of beta sheets. These measurements are consistent with a consensus predictive analysis of the protein sequence suggesting about 28% of helices, 32% of beta sheets and 40% of irregular structure. Brewster angle microscopy (BAM) revealed that, in water, the micelles slowly disaggregate to form a stable and homogeneous layer at the air/water interface, exhibiting a surface pressure up to 10 mN/m. Polarization modulation infrared reflection absorption spectroscopy (PMIRRAS) spectra of interfacial spiralin display a complex amide I band characteristic of a mixture of beta sheets and alpha helices, and an intense amide II band. Spectral simulations indicate a flat orientation for the beta sheets and a vertical orientation for the alpha helices with respect to the interface. The combination of tensiometric and PMIRRAS measurements show that, when spiroplasma lipids are used to form a monolayer at the air/water interface, spiralin is adsorbed under this monolayer and its antiparallel beta sheets are mainly parallel to the polar-head layer of the lipids without deep perturbation of the fatty acid chains organization. Based upon these results, we propose a 'carpet model' for spiralin organization at the spiroplasma cell surface. In this model, spiralin molecules anchored into the outer leaflet of the lipid bilayer by their N-terminal lipid moiety are composed of two colinear domains (instead of a single globular domain) situated at the lipid/water interface. Owing to the very high amount of spiralin in the membrane, such carpets would cover most if not all the lipids present in the outer leaflet of the bilayer.

Ligand reprogramming in dinuclear helicate complexes: a consequence of allosteric or electrostatic effects?

PubMed

Jeffery, John C; Rice, Craig R; Harding, Lindsay P; Baylies, Christian J; Riis-Johannessen, Thomas

2007-01-01

The ditopic ligand 6,6'-bis(4-methylthiazol-2-yl)-3,3'-([18]crown-6)-2,2'-bipyridine (L(1)) contains both a potentially tetradentate pyridyl-thiazole (py-tz) N-donor chain and an additional "external" crown ether binding site which spans the central 2,2'-bipyridine unit. In polar solvents (MeCN, MeNO(2)) this ligand forms complexes with Zn(II), Cd(II), Hg(II) and Cu(I) ions via coordination of the N donors to the metal ion. Reaction with both Hg(II) and Cu(I) ions results in the self-assembly of dinuclear double-stranded helicate complexes. The ligands are partitioned by rotation about the central py--py bond, such that each can coordinate to both metals as a bis-bidentate donor ligand. With Zn(II) ions a single-stranded mononuclear species is formed in which one ligand coordinates the metal ion in a planar tetradentate fashion. Reaction with Cd(II) ions gives rise to an equilibrium between both the dinuclear double-stranded helicate and the mononuclear species. These complexes can further coordinate s-block metal cations via the remote crown ether O-donor domains; a consequence of which are some remarkable changes in the binding modes of the N-donor domains. Reaction of the Hg(II)- or Cd(II)-containing helicate with either Ba(2+) or Sr(2+) ions effectively reprogrammes the ligand to form only the single-stranded heterobinuclear complexes [MM'(L(1))](4+) (M=Hg(II), Cd(II); M'=Ba(2+), Sr(2+)), where the transition and s-block cations reside in the N- and O-donor sites, respectively. In contrast, the same ions have only a minor structural impact on the Zn(II) species, which already exists as a single-stranded mononuclear complex. Similar reactions with the Cd(II) system result in a shift in equilibrium towards the single-stranded species, the extent of which depends on the size and charge of the s-block cation in question. Reaction of the dicopper(I) double-stranded helicate with Ba(2+) shows that the dinuclear structure still remains intact but the pitch length is significantly increased.

Detailed microscopic unfolding pathways of an α-helix and a β-hairpin: direct observation and molecular dynamics.

PubMed

Jas, Gouri S; Hegefeld, Wendy A; Middaugh, C Russell; Johnson, Carey K; Kuczera, Krzysztof

2014-07-03

We present a combined experimental and computational study of unfolding pathways of a model 21-residue α-helical heteropeptide (W1H5-21) and a 16-residue β-hairpin (GB41-56). Experimentally, we measured fluorescence energy transfer efficiency as a function of temperature, employing natural tryptophans as donors and dansylated lysines as acceptors. Secondary structural analysis was performed with circular dichroism and Fourier transform infrared spectroscopy. Our studies present markedly different unfolding pathways of the two elementary secondary structural elements. During thermal denaturation, the helical peptide exhibits an initial decrease in length, followed by an increase, while the hairpin undergoes a systematic increase in length. In the complementary computational part of the project, we performed microsecond length replica-exchange molecular dynamics simulations of the peptides in explicit solvent, yielding a detailed microscopic picture of the unfolding processes. For the α-helical peptide, we found a large heterogeneous population of intermediates that are primarily frayed single helices or helix-turn-helix motifs. Unfolding starts at the termini and proceeds through a stable helical region in the interior of the peptide but shifted off-center toward the C-terminus. The simulations explain the experimentally observed non-monotonic variation of helix length with temperature as due primarily to the presence of frayed-end single-helix intermediate structures. For the β-hairpin peptide, our simulations indicate that folding is initiated at the turn, followed by formation of the hairpin in zipper-like fashion, with Cα···Cα contacts propagating from the turn to termini and hairpin hydrogen bonds forming in parallel with these contacts. In the early stages of hairpin formation, the hydrophobic side-chain contacts are only partly populated. Intermediate structures with low numbers of β-hairpin hydrogen bonds have very low populations. This is in accord with the "broken zipper" model of Scheraga. The monotonic increase in length with temperature may be explained by the zipper-like breaking of the hairpin hydrogen bonds and backbone contacts.

Super-secondary structure peptidomimetics: design and synthesis of an α-α hairpin analogue

PubMed Central

Nevola, Laura; Rodriguez, Johanna M.; Thompson, Sam; Hamilton, Andrew D.

2015-01-01

The α-α helix motif presents key recognition domains in protein-protein and protein-oligonucleotide binding, and is one of the most common super-secondary structures. Herein we describe the design, synthesis and structural characterization of an α-α hairpin analogue based on a tetra-coordinated Pd(II) bis-(iminoisoquinoline) complex as a template for the display of two α-helix mimics. This approach is exemplified by the attachment of two biphenyl peptidomimetics to reproduce the side-chains of the i and i+4 residues of two helices. PMID:26052191

[Zn(INO) 2(DMF)]·DMF: A new three-dimensional supramolecular open framework containing one-dimensional channels

NASA Astrophysics Data System (ADS)

Hong, Jun

2006-02-01

A three-dimensional supramolecular compound, [Zn(INO) 2(DMF)]·DMF (1) (INO=isonicotinic acid N-oxide), has been prepared in the DMF solution at room temperature, and characterized by elemental analysis, TG and single crystal X-ray diffraction. The three-dimensional supramolecular open framework of 1 contains rectangular channels with the dimensions of 9.02×10.15 Å, assembled from one-dimensional helical chains via hydrogen-bonding and π-π stacking interactions. Furthermore, compound 1 shows blue photoluminescence at room temperature.

(2SR,3RS)-Benz­yl[4-chloro-1-(4-chloro­phen­yl)-1-methoxy­carbon­yl-2-but­yl]­ammonium chloride

PubMed Central

Kaupang, Åsmund; Bolsønes, Marianne; Gamadeku, Thywill; Hansen, Tore; Hennum, Martin Johanson; Görbitz, Carl Henrik

2008-01-01

In the racemic hydro­chloride salt of the title ester, C19H22Cl2NO2 +·Cl−, the penta­noic acid chain shows a mixture of trans and gauche orientations to give an overall helical conformation. The dihedral angle between the two aromatic rings is 26.11 (10)°. The charged secondary amine function participates in two N—H⋯Cl hydrogen bonds. PMID:21201230

Crystal Structure of a Four-Layer Aggregate of Engineered TMV CP Implies the Importance of Terminal Residues for Oligomer Assembly

PubMed Central

Li, Xiangyang; Song, Baoan; Chen, Xi; Wang, Zhenchao; Zeng, Mengjiao; Yu, Dandan; Hu, Deyu; Chen, Zhuo; Jin, Linhong; Yang, Song; Yang, Caiguang; Chen, Baoen

2013-01-01

Background Crystal structures of the tobacco mosaic virus (TMV) coat protein (CP) in its helical and disk conformations have previously been determined at the atomic level. For the helical structure, interactions of proteins and nucleic acids in the main chains were clearly observed; however, the conformation of residues at the C-terminus was flexible and disordered. For the four-layer aggregate disk structure, interactions of the main chain residues could only be observed through water–mediated hydrogen bonding with protein residues. In this study, the effects of the C-terminal peptides on the interactions of TMV CP were investigated by crystal structure determination. Methodology/Principal Findings The crystal structure of a genetically engineered TMV CP was resolved at 3.06 Å. For the genetically engineered TMV CP, a six-histidine (His) tag was introduced at the N-terminus, and the C-terminal residues 155 to 158 were truncated (N-His-TMV CP19). Overall, N-His-TMV CP19 protein self-assembled into the four-layer aggregate form. The conformations of residues Gln36, Thr59, Asp115 and Arg134 were carefully analyzed in the high radius and low radius regions of N-His-TMV CP19, which were found to be significantly different from those observed previously for the helical and four-layer aggregate forms. In addition, the aggregation of the N-His-TMV CP19 layers was found to primarily be mediated through direct hydrogen-bonding. Notably, this engineered protein also can package RNA effectively and assemble into an infectious virus particle. Conclusion The terminal sequence of amino acids influences the conformation and interactions of the four-layer aggregate. Direct protein–protein interactions are observed in the major overlap region when residues Gly155 to Thr158 at the C-terminus are truncated. This engineered TMV CP is reassembled by direct protein–protein interaction and maintains the normal function of the four-layer aggregate of TMV CP in the presence of RNA. PMID:24223721

Ligand Binding Properties of the Lentil Lipid Transfer Protein: Molecular Insight into the Possible Mechanism of Lipid Uptake.

PubMed

Shenkarev, Zakhar O; Melnikova, Daria N; Finkina, Ekaterina I; Sukhanov, Stanislav V; Boldyrev, Ivan A; Gizatullina, Albina K; Mineev, Konstantin S; Arseniev, Alexander S; Ovchinnikova, Tatiana V

2017-03-28

The lentil lipid transfer protein, designated as Lc-LTP2, was isolated from Lens culinaris seeds. The protein belongs to the LTP1 subfamily and consists of 93 amino acid residues. Its spatial structure includes four α-helices (H1-H4) and a long C-terminal tail. Here, we report the ligand binding properties of Lc-LTP2. The fluorescent 2-p-toluidinonaphthalene-6-sulfonate binding assay revealed that the affinity of Lc-LTP2 for saturated and unsaturated fatty acids was enhanced with a decrease in acyl-chain length. Measurements of boundary potential in planar lipid bilayers and calcein dye leakage in vesicular systems revealed preferential interaction of Lc-LTP2 with the negatively charged membranes. Lc-LTP2 more efficiently transferred anionic dimyristoylphosphatidylglycerol (DMPG) than zwitterionic dimyristoylphosphatidylcholine. Nuclear magnetic resonance experiments confirmed the higher affinity of Lc-LTP2 for anionic lipids and those with smaller volumes of hydrophobic chains. The acyl chains of the bound lysopalmitoylphosphatidylglycerol (LPPG), DMPG, or dihexanoylphosphatidylcholine molecules occupied the internal hydrophobic cavity, while their headgroups protruded into the aqueous environment between helices H1 and H3. The spatial structure and backbone dynamics of the Lc-LTP2-LPPG complex were determined. The internal cavity was expanded from ∼600 to ∼1000 Å 3 upon the ligand binding. Another entrance into the internal cavity, restricted by the H2-H3 interhelical loop and C-terminal tail, appeared to be responsible for the attachment of Lc-LTP2 to the membrane or micelle surface and probably played an important role in the lipid uptake determining the ligand specificity. Our results confirmed the previous assumption regarding the membrane-mediated antimicrobial action of Lc-LTP2 and afforded molecular insight into its biological role in the plant.

The coupling effects of kinematics and flexibility on the Lagrangian dynamic formulation of open chain deformable links

NASA Technical Reports Server (NTRS)

Changizi, Koorosh

1989-01-01

A nonlinear Lagrangian formulation for the spatial kinematic and dynamic analysis of open chain deformable links consisting of cylindrical joints that connect pairs of flexible links is developed. The special cases of revolute or prismatic joint can also be obtained from the kinematic equations. The kinematic equations are described using a 4x4 matrix method. The configuration of each deformable link in the open loop kinematic chain is identified using a coupled set of relative joint variables, constant geometric parameters, and elastic coordinates. The elastic coordinates define the link deformation with respect to a selected joint coordinate system that is consistent with the kinematic constraints on the boundary of the deformable link. These coordinates can be introduced using approximation techniques such as Rayleigh-Ritz method, finite element technique or any other desired approach. The large relative motion between two neighboring links are defined by a set of joint coordinates which describes the large relative translational and rotational motion between two neighboring joint coordinate systems. The origin of these coordinate systems are rigidly attached to the neighboring links at the joint definition points along the axis of motion.

Enzymatically cross-linked tilapia gelatin hydrogels: physical, chemical, and hybrid networks.

PubMed

Bode, Franziska; da Silva, Marcelo Alves; Drake, Alex F; Ross-Murphy, Simon B; Dreiss, Cécile A

2011-10-10

This Article investigates different types of networks formed from tilapia fish gelatin (10% w/w) in the presence and absence of the enzymatic cross-linker microbial transglutaminase. The influence of the temperature protocol and cross-linker concentration (0-55 U mTGase/g gelatin) was examined in physical, chemical, and hybrid gels, where physical gels arise from the formation of triple helices that act as junction points when the gels are cooled below the gelation point. A combination of rheology and optical rotation was used to study the evolution of the storage modulus (G') over time and the number of triple helices formed for each type of gel. We attempted to separate the final storage modulus of the gels into its chemical and physical contributions to examine the existence or otherwise of synergism between the two types of networks. Our experiments show that the gel characteristics vary widely with the thermal protocol. The final storage modulus in chemical gels increased with enzyme concentration, possibly due to the preferential formation of closed loops at low cross-linker amount. In chemical-physical gels, where the physical network (helices) was formed consecutively to the covalent one, we found that below a critical enzyme concentration the more extensive the chemical network is (as measured by G'), the weaker the final gel is. The storage modulus attributed to the physical network decreased exponentially as a function of G' from the chemical network, but both networks were found to be purely additive. Helices were not thermally stabilized. The simultaneous formation of physical and chemical networks (physical-co-chemical) resulted in G' values higher than the individual networks formed under the same conditions. Two regimes were distinguished: at low enzyme concentration (10-20 U mTGase/g gelatin), the networks were formed in series, but the storage modulus from the chemical network was higher in the presence of helices (compared to pure chemical gels); at higher enzyme concentration (30-40 U mTGase/g gelatin), strong synergistic effects were found as a large part of the covalent network became ineffective upon melting of the helices.

Interaction of cholesterol with sphingomyelins and acyl-chain-matched phosphatidylcholines: a comparative study of the effect of the chain length.

PubMed Central

Ramstedt, B; Slotte, J P

1999-01-01

In this study we have synthesized sphingomyelins (SM) and phosphatidylcholines (PC) with amide-linked or sn-2 linked acyl chains with lengths from 14 to 24 carbons. The purpose was to examine how the chain length and degree of unsaturation affected the interaction of cholesterol with these phospholipids in model membrane systems. Monolayers of saturated SMs and PCs with acyl chain lengths above 14 carbons were condensed and displayed a high collapse pressure ( approximately 70 mN/m). Monolayers of N-14:0-SM and 1(16:0)-2(14:0)-PC had a much lower collapse pressure (58-60 mN/m) and monounsaturated SMs collapsed at approximately 50 mN/m. The relative interaction of cholesterol with these phospholipids was determined at 22 degreesC by measuring the rate of cholesterol desorption from mixed monolayers (50 mol % cholesterol; 20 mN/m) to beta-cyclodextrin in the subphase (1.7 mM). The rate of cholesterol desorption was lower from saturated SM monolayers than from chain-matched PC monolayers. In SM monolayers, the rate of cholesterol desorption was very slow for all N-linked chains, whereas for PC monolayers we could observe higher desorption rates from monolayers of longer PCs. These results show that cholesterol interacts favorably with SMs (low rate of desorption), whereas its interaction (or miscibility) with long chain PCs is weaker. Introduction of a single cis-unsaturation in the N-linked acyl chain of SMs led to faster rates of cholesterol desorption as compared with saturated SMs. The exception was monolayers of N-22:1-SM and N-24:1-SM from which cholesterol desorbed almost as slowly as from the corresponding saturated SM monolayers. The results of this study suggest that cholesterol is most likely capable of interacting with all physiologically relevant (including long-chain) SMs present in the plasma membrane of cells. PMID:9929492

Comparison of the crystal structures of methyl 4-bromo-2-(meth-oxy-meth-oxy)benzoate and 4-bromo-3-(meth-oxy-meth-oxy)benzoic acid.

PubMed

Suchetan, P A; Suneetha, V; Naveen, S; Lokanath, N K; Krishna Murthy, P

2016-04-01

The title compounds, C10H11BrO4, (I), and C9H9BrO4, (II), are derivatives of bromo-hy-droxy-benzoic acids. Compound (II) crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. In both (I) and (II), the O-CH2-O-CH3 side chain is not in its fully extended conformation; the O-C-O-C torsion angle is 67.3 (3) ° in (I), and -65.8 (3) and -74.1 (3)° in mol-ecules A and B, respectively, in compound (II). In the crystal of (I), mol-ecules are linked by C-H⋯O hydrogen bonds, forming C(5) chains along [010]. The chains are linked by short Br⋯O contacts [3.047 (2) Å], forming sheets parallel to the bc plane. The sheets are linked via C-H⋯π inter-actions, forming a three-dimensional architecture. In the crystal of (II), mol-ecules A and B are linked to form R 2 (2)(8) dimers via two strong O-H⋯O hydrogen bonds. These dimers are linked into ⋯A-B⋯A-B⋯A-B⋯ [C 2 (2)(15)] chains along [011] by C-H⋯O hydrogen bonds. The chains are linked by slipped parallel π-π inter-actions [inter-centroid distances = 3.6787 (18) and 3.8431 (17) Å], leading to the formation of slabs parallel to the bc plane.

Crystal structures of three 3,4,5-tri-meth-oxy-benzamide-based derivatives.

PubMed

Gomes, Ligia R; Low, John Nicolson; Oliveira, Catarina; Cagide, Fernando; Borges, Fernanda

2016-05-01

The crystal structures of three benzamide derivatives, viz. N-(6-hy-droxy-hex-yl)-3,4,5-tri-meth-oxy-benzamide, C16H25NO5, (1), N-(6-anilinohex-yl)-3,4,5-tri-meth-oxy-benzamide, C22H30N2O4, (2), and N-(6,6-di-eth-oxy-hex-yl)-3,4,5-tri-meth-oxy-benzamide, C20H33NO6, (3), are described. These compounds differ only in the substituent at the end of the hexyl chain and the nature of these substituents determines the differences in hydrogen bonding between the mol-ecules. In each mol-ecule, the m-meth-oxy substituents are virtually coplanar with the benzyl ring, while the p-meth-oxy substituent is almost perpendicular. The carbonyl O atom of the amide rotamer is trans related with the amidic H atom. In each structure, the benzamide N-H donor group and O acceptor atoms link the mol-ecules into C(4) chains. In 1, a terminal -OH group links the mol-ecules into a C(3) chain and the combined effect of the C(4) and C(3) chains is a ribbon made up of screw related R 2 (2)(17) rings in which the ⋯O-H⋯ chain lies in the centre of the ribbon and the tri-meth-oxy-benzyl groups forms the edges. In 2, the combination of the benzamide C(4) chain and the hydrogen bond formed by the terminal N-H group to an O atom of the 4-meth-oxy group link the mol-ecules into a chain of R 2 (2)(17) rings. In 3, the mol-ecules are linked only by C(4) chains.

Optical probe for the cytochrome P-450 cholesterol side chain cleavage enzyme

DOEpatents

Marrone, Babetta L.; Simpson, Daniel J.; Unkefer, Clifford J.; Whaley, Thomas W.

1992-01-01

An optical probe enables the study of enzyme activity by absorbance spectroscopy or by sensitive fluorescence methods. In particular, the probe provides the ability to monitor the activity of cytochrome P-450.sub.scc enzyme, the rate limiting enzyme for steroid biosynthesis. Located on the inner mitochondrial membrane, P-450.sub.scc catalyzes the conversion of cholesterol to pregnenolone and isocapraldehyde by sequential oxidations of the cholesterol side chain. The fluorogenic probe includes a cholesterol-like steroid linked to a chromophore through a linking group. The chromophore is selected to have little optical response when linked to the steroid substrate and an enhanced optical response when cleaved from the substrate and linking group. Thus, a fluorescent anion that can be optically detected is generated by the side-chain cleavage reaction during steroidogenesis.

Optical probe for the cytochrome P-450 cholesterol side chain cleavage enzyme

DOEpatents

Marrone, Babetta L.; Simpson, Daniel J.; Unkefer, Clifford J.; Whaley, Thomas W.

1993-01-01

An optical probe enables the study of enzyme activity by absorbance spectroscopy or by sensitive fluorescence methods. In particular, the probe provides the ability to monitor the activity of cytochrome P-450.sub.scc enzyme, the rate limiting enzyme for steroid biosynthesis. Located on the inner mitochondrial membrane, P-450.sub.scc catalyzes the conversion of cholesterol to pregnenolone and isocapraldehyde by sequential oxidations of the cholesterol side chain. The fluorogenic probe includes a cholesterol-like steroid linked to a chromophore through a linking group. The chromophore is selected to have little optical response when linked to the steroid substrate and an enhanced optical response when cleaved from the substrate and linking group. Thus, a fluorescent anion that can be optically detected is generated by the side-chain cleavage reaction during steroidogenesis.

Self-generated covalent cross-links in the cell-surface adhesins of Gram-positive bacteria.

PubMed

Baker, Edward N; Squire, Christopher J; Young, Paul G

2015-10-01

The ability of bacteria to adhere to other cells or to surfaces depends on long, thin adhesive structures that are anchored to their cell walls. These structures include extended protein oligomers known as pili and single, multi-domain polypeptides, mostly based on multiple tandem Ig-like domains. Recent structural studies have revealed the widespread presence of covalent cross-links, not previously seen within proteins, which stabilize these domains. The cross-links discovered so far are either isopeptide bonds that link lysine side chains to the side chains of asparagine or aspartic acid residues or ester bonds between threonine and glutamine side chains. These bonds appear to be formed by spontaneous intramolecular reactions as the proteins fold and are strategically placed so as to impart considerable mechanical strength. © 2015 Authors; published by Portland Press Limited.

Maximum Kolmogorov-Sinai Entropy Versus Minimum Mixing Time in Markov Chains

NASA Astrophysics Data System (ADS)

Mihelich, M.; Dubrulle, B.; Paillard, D.; Kral, Q.; Faranda, D.

2018-01-01

We establish a link between the maximization of Kolmogorov Sinai entropy (KSE) and the minimization of the mixing time for general Markov chains. Since the maximisation of KSE is analytical and easier to compute in general than mixing time, this link provides a new faster method to approximate the minimum mixing time dynamics. It could be interesting in computer sciences and statistical physics, for computations that use random walks on graphs that can be represented as Markov chains.

Effect of pendent chains on the interfacial properties of thin polydimethylsiloxane (PDMS) networks.

PubMed

Landherr, Lucas J T; Cohen, Claude; Archer, Lynden A

2011-05-17

The interfacial properties of end-linked polydimethylsiloxane (PDMS) films on silicon are examined. Thin cross-linked PDMS films (∼10 μm thick) were synthesized over a self-assembled monolayer supported on a silicon wafer. By systematically varying the concentration of monofunctional PDMS in a mixture with telechelic precursor molecules, structures ranging from near-ideal elastic networks to poorly cross-linked networks composed of a preponderance of dangling/pendent chains were synthesized. Lateral force microscopy (LFM) employing bead probes was used to quantify the effect of network structure on the interfacial friction coefficient and residual force. Indentation measurements employing an AFM in force mode were used to characterize the elastic modulus and the pull-off force for the films as a function of pendent chain content. These measurements were complemented with conventional mechanical rheometry measurements on similar thick network films to determine their bulk rheological properties. All networks studied manifested interfacial friction coefficients substantially lower than that of bare silicon. PDMS networks with the lowest pendent chain content displayed friction coefficients close to 1 order of magnitude lower than that of bare silicon, whereas networks with the highest pendent chain content manifested friction coefficients about 3 times lower than that of bare silicon. At intermediate sliding velocities, a crossover in the interfacial friction coefficient was observed, wherein cross-linked PDMS films with the least amount of pendent chains exhibit the highest friction coefficient. These observations are discussed in terms of the structure of the films and relaxation dynamics of elastic strands and dangling chains in tethered network films.

Choice and conditioned reinforcement.

PubMed Central

Fantino, E; Freed, D; Preston, R A; Williams, W A

1991-01-01

A potential weakness of one formulation of delay-reduction theory is its failure to include a term for rate of conditioned reinforcement, that is, the rate at which the terminal-link stimuli occur in concurrent-chains schedules. The present studies assessed whether or not rate of conditioned reinforcement has an independent effect upon choice. Pigeons responded on either modified concurrent-chains schedules or on comparable concurrent-tandem schedules. The initial link was shortened on only one of two concurrent-chains schedules and on only one of two corresponding concurrent-tandem schedules. This manipulation increased rate of conditioned reinforcement sharply in the chain but not in the tandem schedule. According to a formulation of delay-reduction theory, when the outcomes chosen (the terminal links) are equal, as in Experiment 1, choice should depend only on rate of primary reinforcement; thus, choice should be equivalent for the tandem and chain schedules despite a large difference in rate of conditioned reinforcement. When the outcomes chosen are unequal, however, as in Experiment 2, choice should depend upon both rate of primary reinforcement and relative signaled delay reduction; thus, larger preferences should occur in the chain than in the tandem schedules. These predictions were confirmed, suggesting that increasing the rate of conditioned reinforcement on concurrent-chains schedules may have no independent effect on choice. PMID:2037826

The Chain-Link Fence Model: A Framework for Creating Security Procedures

ERIC Educational Resources Information Center

Houghton, Robert F.

2013-01-01

A long standing problem in information technology security is how to help reduce the security footprint. Many specific proposals exist to address specific problems in information technology security. Most information technology solutions need to be repeatable throughout the course of an information systems lifecycle. The Chain-Link Fence Model is…

Design and characterization of the anion-sensitive coiled-coil peptide.

PubMed Central

Hoshino, M.; Yumoto, N.; Yoshikawa, S.; Goto, Y.

1997-01-01

As a model for analyzing the role of charge repulsion in proteins and its shielding by the solvent, we designed a peptide of 27 amino acid residues that formed a homodimeric coiled-coil. The interface between the coils consisted of hydrophobic Leu and Val residues, and 10 Lys residues per monomer were incorporated into the positions exposed to solvent. During the preparation of a disulfide-linked dimer in which the two peptides were linked in parallel by the two disulfide bonds located at the N and C terminals, a cyclic monomer with an intramolecular disulfide bond was also obtained. On the basis of CD and 1H-NMR, the conformational stabilities of these isomers and several reference peptides were examined. Whereas all these peptides were unfolded in the absence of salt at pH 4.7 and 20 degrees C, the addition of NaClO4 cooperatively stabilized the alpha-helical conformation. The crosslinking of the peptides by disulfide bonds significantly decreased the midpoint salt concentration of the transition. The 1H-NMR spectra in the presence of NaClO4 suggested that, whereas the disulfide-bonded dimer assumed a native-like conformation, the cyclic monomer assumed a molten globule-like conformation with disordered side chains. However, the cyclic monomer exhibited cooperative transitions against temperature and Gdn-HCl that were only slightly less cooperative than those of the disulfide-bonded parallel dimer. These results indicate that the charge repulsion critically destabilizes the native-like state as well as the molten globule-like state, and that the solvent-dependent charge repulsion may be useful for controlling the conformation of designed peptides. PMID:9232640

Interfacial friction and adhesion of cross-linked polymer thin films swollen with linear chains.

PubMed

Zhang, Qing; Archer, Lynden A

2007-07-03

The preparation and interfacial properties of a new type of tethered, thin-film lubricant coating are presented. These coatings are composed of three components: a dense self-assembled monolayer (SAM) underlayer that presents reactive vinyl groups at its surface; a cross-linked polydimethylsiloxane (PDMS) overlayer that is covalently tethered to the SAM; and free, mobile linear PDMS chains dispersed in the network. We investigate the influence of the molecular weight (Ms) and concentration of the free PDMS chains on the structure and equilibrium swelling properties of the cross-linked films. Using a bead-probe lateral force microscopy measurement technique, we also quantify the interfacial friction and adhesion characteristics of surfaces functionalized with these coatings. We find that both the volume fraction and the molecular weight of free PDMS molecules in the coatings influence their interfacial friction and adhesion properties. For example, the addition of short PDMS chains in dry, cross-linked PDMS thin films yields tethered surface coatings with ultralow friction coefficients (mu = 5.2 x 10(-3)). An analysis based on classical lubrication theory suggests that the reduction in friction force produced by free polymer is a consequence of the gradual separation of asperities on opposing surfaces and the consequent substitution of solid-solid friction by viscous drag of the free polymer chains in the network.

Novel polyubiquitin imaging system, PolyUb-FC, reveals that K33-linked polyubiquitin is recruited by SQSTM1/p62.

PubMed

Nibe, Yoichi; Oshima, Shigeru; Kobayashi, Masanori; Maeyashiki, Chiaki; Matsuzawa, Yu; Otsubo, Kana; Matsuda, Hiroki; Aonuma, Emi; Nemoto, Yasuhiro; Nagaishi, Takashi; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Nakada, Shinichiro; Watanabe, Mamoru

2018-01-01

Ubiquitin chains are formed with 8 structurally and functionally distinct polymers. However, the functions of each polyubiquitin remain poorly understood. We developed a polyubiquitin-mediated fluorescence complementation (PolyUb-FC) assay using Kusabira Green (KG) as a split fluorescent protein. The PolyUb-FC assay has the advantage that monoubiquitination is nonfluorescent and chain-specific polyubiquitination can be directly visualized in living cells without using antibodies. We applied the PolyUb-FC assay to examine K33-linked polyubiquitin. We demonstrated that SQSTM1/p62 puncta colocalized with K33-linked polyubiquitin and this interaction was modulated by the ZRANB1/TRABID-K29 and -K33 linkage-specific deubiquitinase (DUB). We further showed that the colocalization of K33-linked polyubiquitin and MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) puncta was impaired by SQSTM1/p62 deficiency. Taken together, these findings provide novel insights into how atypical polyubiquitin is recruited by SQSTM1/p62. Finally, we developed an inducible-PolyUb-FC system for visualizing chain-specific polyubiquitin. The PolyUb-FC will be a useful tool for analyzing the dynamics of atypical polyubiquitin chain generation.

Large-scale models reveal the two-component mechanics of striated muscle.

PubMed

Jarosch, Robert

2008-12-01

This paper provides a comprehensive explanation of striated muscle mechanics and contraction on the basis of filament rotations. Helical proteins, particularly the coiled-coils of tropomyosin, myosin and alpha-actinin, shorten their H-bonds cooperatively and produce torque and filament rotations when the Coulombic net-charge repulsion of their highly charged side-chains is diminished by interaction with ions. The classical "two-component model" of active muscle differentiated a "contractile component" which stretches the "series elastic component" during force production. The contractile components are the helically shaped thin filaments of muscle that shorten the sarcomeres by clockwise drilling into the myosin cross-bridges with torque decrease (= force-deficit). Muscle stretch means drawing out the thin filament helices off the cross-bridges under passive counterclockwise rotation with torque increase (= stretch activation). Since each thin filament is anchored by four elastic alpha-actinin Z-filaments (provided with force-regulating sites for Ca(2+) binding), the thin filament rotations change the torsional twist of the four Z-filaments as the "series elastic components". Large scale models simulate the changes of structure and force in the Z-band by the different Z-filament twisting stages A, B, C, D, E, F and G. Stage D corresponds to the isometric state. The basic phenomena of muscle physiology, i. e. latency relaxation, Fenn-effect, the force-velocity relation, the length-tension relation, unexplained energy, shortening heat, the Huxley-Simmons phases, etc. are explained and interpreted with the help of the model experiments.

Essential arginine in subunit a and aspartate in subunit c of FoF1 ATP synthase: effect of repositioning within helix 4 of subunit a and helix 2 of subunit c.

PubMed

Langemeyer, Lars; Engelbrecht, Siegfried

2007-07-01

FoF1 ATP synthase couples proton flow through the integral membrane portion Fo (ab2c10) to ATP-synthesis in the extrinsic F1-part ((alphabeta)3gammadeltaepsilon) (Escherichia coli nomenclature and stoichiometry). Coupling occurs by mechanical rotation of subunits c10gammaepsilon relative to (alphabeta)3deltaab2. Two residues were found to be essential for proton flow through ab2c10, namely Arg210 in subunit a (aR210) and Asp61 in subunits c (cD61). Their deletion abolishes proton flow, but "horizontal" repositioning, by anchoring them in adjacent transmembrane helices, restores function. Here, we investigated the effects of "vertical" repositioning aR210, cD61, or both by one helical turn towards the N- or C-termini of their original helices. Other than in the horizontal the vertical displacement changes the positions of the side chains within the depth of the membrane. Mutant aR210A/aN214R appeared to be short-circuited in that it supported proton conduction only through EF1-depleted EFo, but not in EFoEF1, nor ATP-driven proton pumping. Mutant cD61N/cM65D grew on succinate, retained the ability to synthesize ATP and supported passive proton conduction but apparently not ATP hydrolysis-driven proton pumping.

Crystal Structure of Glycoside Hydrolase Family 55 β-1,3-Glucanase from the Basidiomycete Phanerochaete chrysosporium*S⃞

PubMed Central

Ishida, Takuya; Fushinobu, Shinya; Kawai, Rie; Kitaoka, Motomitsu; Igarashi, Kiyohiko; Samejima, Masahiro

2009-01-01

Glycoside hydrolase family 55 consists of β-1,3-glucanases mainly from filamentous fungi. A β-1,3-glucanase (Lam55A) from the Basidiomycete Phanerochaete chrysosporium hydrolyzes β-1,3-glucans in the exo-mode with inversion of anomeric configuration and produces gentiobiose in addition to glucose from β-1,3/1,6-glucans. Here we report the crystal structure of Lam55A, establishing the three-dimensional structure of a member of glycoside hydrolase 55 for the first time. Lam55A has two β-helical domains in a single polypeptide chain. These two domains are separated by a long linker region but are positioned side by side, and the overall structure resembles a rib cage. In the complex, a gluconolactone molecule is bound at the bottom of a pocket between the two β-helical domains. Based on the position of the gluconolactone molecule, Glu-633 appears to be the catalytic acid, whereas the catalytic base residue could not be identified. The substrate binding pocket appears to be able to accept a gentiobiose unit near the cleavage site, and a long cleft runs from the pocket, in accordance with the activity of this enzyme toward various β-1,3-glucan oligosaccharides. In conclusion, we provide important features of the substrate-binding site at the interface of the two β-helical domains, demonstrating an unexpected variety of carbohydrate binding modes. PMID:19193645

Orientation Preferences of Backbone Secondary Amide Functional Groups in Peptide Nucleic Acid Complexes: Quantum Chemical Calculations Reveal an Intrinsic Preference of Cationic D-Amino Acid-Based Chiral PNA Analogues for the P-form

PubMed Central

Topham, Christopher M.; Smith, Jeremy C.

2007-01-01

Geometric descriptions of nonideal interresidue hydrogen bonding and backbone-base water bridging in the minor groove are established in terms of polyamide backbone carbonyl group orientation from analyses of residue junction conformers in experimentally determined peptide nucleic acid (PNA) complexes. Two types of interresidue hydrogen bonding are identified in PNA conformers in heteroduplexes with nucleic acids that adopt A-like basepair stacking. Quantum chemical calculations on the binding of a water molecule to an O2 base atom in glycine-based PNA thymine dimers indicate that junctions modeled with P-form backbone conformations are lower in energy than a dimer comprising the predominant conformation observed in A-like helices. It is further shown in model systems that PNA analogs based on D-lysine are better able to preorganize in a conformation exclusive to P-form helices than is glycine-based PNA. An intrinsic preference for this conformation is also exhibited by positively charged chiral PNA dimers carrying 3-amino-D-alanine or 4-aza-D-leucine residue units that provide for additional rigidity by side-chain hydrogen bonding to the backbone carbonyl oxygen. Structural modifications stabilizing P-form helices may obviate the need for large heterocycles to target DNA pyrimidine bases via PNA·DNA-PNA triplex formation. Quantum chemical modeling methods are used to propose candidate PNA Hoogsteen strand designs. PMID:17071666

Large-scale Models Reveal the Two-component Mechanics of Striated Muscle

PubMed Central

Jarosch, Robert

2008-01-01

This paper provides a comprehensive explanation of striated muscle mechanics and contraction on the basis of filament rotations. Helical proteins, particularly the coiled-coils of tropomyosin, myosin and α-actinin, shorten their H-bonds cooperatively and produce torque and filament rotations when the Coulombic net-charge repulsion of their highly charged side-chains is diminished by interaction with ions. The classical “two-component model” of active muscle differentiated a “contractile component” which stretches the “series elastic component” during force production. The contractile components are the helically shaped thin filaments of muscle that shorten the sarcomeres by clockwise drilling into the myosin cross-bridges with torque decrease (= force-deficit). Muscle stretch means drawing out the thin filament helices off the cross-bridges under passive counterclockwise rotation with torque increase (= stretch activation). Since each thin filament is anchored by four elastic α-actinin Z-filaments (provided with force-regulating sites for Ca2+ binding), the thin filament rotations change the torsional twist of the four Z-filaments as the “series elastic components”. Large scale models simulate the changes of structure and force in the Z-band by the different Z-filament twisting stages A, B, C, D, E, F and G. Stage D corresponds to the isometric state. The basic phenomena of muscle physiology, i. e. latency relaxation, Fenn-effect, the force-velocity relation, the length-tension relation, unexplained energy, shortening heat, the Huxley-Simmons phases, etc. are explained and interpreted with the help of the model experiments. PMID:19330099

Helicity, geostrophic balance and mixing in rotating stratified turbulence: a multi-scale problem

NASA Astrophysics Data System (ADS)

Pouquet, A.; Marino, R.; Mininni, P.; Rorai, C.; Rosenberg, D. L.

2012-12-01

Helicity, geostrophic balance and mixing in rotating stratified turbulence: a multi-scale problem A. Pouquet, R. Marino, P. D. Mininni, C. Rorai & D. Rosenberg, NCAR Interactions between winds and waves have important roles in planetary and oceanic boundary layers, affecting momentum, heat and CO2 transport. Within the Abyssal Southern Ocean at Mid latitude, this may result in a mixed layer which is too shallow in climate models thereby affecting the overall evolution because of poor handling of wave breaking as in Kelvin-Helmoltz instabilities: gravity waves couple nonlinearly on slow time scales and undergo steepening through resonant interactions, or due to the presence of shear. In the oceans, sub-mesoscale frontogenesis and significant departure from quasi-geostrophy can be seen as turbulence intensifies. The ensuing anomalous vertical dispersion may not be simply modeled by a random walk, due to intermittent structures, wave propagation and to their interactions. Conversely, the energy and seeds required for such intermittent events to occur, say in the stable planetary boundary layer, may come from the wave field that is perturbed, or from winds and the effect of topography. Under the assumption of stationarity, weak nonlinearities, dissipation and forcing, one obtains large-scale geostrophic balance linking pressure gradient, gravity and Coriolis force. The role of helicity (velocity-vorticity correlations) has not received as much attention, outside the realm of astrophysics when considering the growth of large-scale magnetic fields. However, it is measured routinely in the atmosphere in order to gauge the likelihood of supercell convective storms to strengthen, and it may be a factor to consider in the formation of hurricanes. In this context, we examine the transition from a wave-dominated regime to an isotropic small-scale turbulent one in rotating flows with helical forcing. Using a direct numerical simulation (DNS) on a 3072^3 grid with Rossby and Reynolds numbers of 0.07 and 27000, one can resolve both the Zeman scale at which the inertial and eddy turn-over times equalize, and the dissipation scale. We show that fully helical vertical columns dominate at intermediate scales, presumably self-similar and shrouded by a sea of small-scale vortex filaments as in Kolmogorov turbulence. Helicity has a profound effect on the structures of the flow, and a previously developed model that includes a helical component in its eddy viscosity and eddy noise shows a measurable improvement. Indeed, if dimensionless parameters for inertial and gravity waves are reachable numerically, the Reynolds number is too low in DNS for geophysics unless one uses parametrizations of small scale interactions. For spin-down stably-stratified flows, energy and helicity undergo a substantially slower decay than in the unstratified case, and a type of large-scale cyclostrophic balance is invoked to explain this behavior. The decay rate is similar to that occurring in the unstratified rotating case, as modeled by taking into account the quasi-conservation of helicity. We finally mention helicity production when rotation and stratification are both combined. In conclusion, much remains to be done, e.g. examining transport properties of rotating stratified turbulence, such as the effect of helicity on mixing in geophysical flows that can be studied with high-performance computing allowing multi-scale interactions and intermittency to develop.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Hyock Joo; Abi-Mosleh, Lina; Wang, Michael L.

LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3{beta}-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 25-hydroxycholesterol. NPC1(NTD) binds cholesterol in an orientation opposite to NPC2: 3{beta}-hydroxyl buried and isooctyl side chain exposed. Cholesterol transfer from NPC2 to NPC1(NTD) requires reorientation of a helical subdomain in NPC1(NTD), enlarging the opening for cholesterol entry. NPC1 with point mutations in this subdomain (distinct from themore » binding subdomain) cannot accept cholesterol from NPC2 and cannot restore cholesterol exit from lysosomes in NPC1-deficient cells. We propose a working model wherein after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes.« less

Investigation of the effect of erythrosine B on amyloid beta peptide using molecular modeling.

PubMed

Lee, Juho; Kwon, Inchan; Jang, Seung Soon; Cho, Art E

2016-04-01

Neurotoxic plaques composed of 39 to 42 residue-long amyloid beta peptides (Aβs) are copiously present in the brains of patients with Alzheimer's disease (AD). Erythrosine B (ER), a xanthene food dye, inhibits the formation of Aβ fibrils and Aβ-associated cytotoxicity in vitro. Here, in an attempt to elucidate the inhibition mechanism, we performed molecular dynamics (MD) simulations to demonstrate the conformational change of Aβ40 induced by ER molecules in atomistic detail. During the simulation, the ER bound to the surfaces of both N-terminus and C-terminus regions of Aβ40. Our result shows that ER interacts with the aromatic side chains at the N-terminus region resulting in destabilization of the inter-chain stacking of Aβ40. Moreover, the stablility of the helical structures at the residues from 13 to 16 suggests that ER disturbs conformational transition of Aβ40. At the C-terminus region, the bound ER blocks water molecules and stabilizes the α-helical structure. Regardless of the number of ER molecules used, the interruption of the formation of the salt-bridge between aspartic acid 23 and lysine 28 occurred. To further validate our analysis, binding free energies of ER at each binding site were evaluated. The finding of stronger binding energy at the N-terminus region supports an inhibition mechanism induced by stacking interaction between ER and phenylalanine. These findings could aid present and future treatment studies for AD by clarifying the inhibition mechanism of ER on the conformational transition of Aβ40 at the molecular level.