Sample records for wall binding domains

  1. A small cellulose binding domain protein in Phytophtora is cell wall localized

    USDA-ARS?s Scientific Manuscript database

    Cellulose binding domains (CBD) are structurally conserved regions linked to catalytic regions of cellulolytic enzymes. While widespread amongst saprophytic fungi that subsist on plant cell wall polysaccharides, they are not generally present in plant pathogenic fungi. A genome wide survey of CBDs w...

  2. The Most Abundant Glycoprotein of Amebic Cyst Walls (Jacob) Is a Lectin with Five Cys-Rich, Chitin-Binding Domains

    PubMed Central

    Frisardi, Marta; Ghosh, Sudip K.; Field, Jessica; Van Dellen, Katrina; Rogers, Rick; Robbins, Phillips; Samuelson, John

    2000-01-01

    The infectious stage of amebae is the chitin-walled cyst, which is resistant to stomach acids. In this study an extraordinarily abundant, encystation-specific glycoprotein (Jacob) was identified on two-dimensional protein gels of cyst walls purified from Entamoeba invadens. Jacob, which was acidic and had an apparent molecular mass of ∼100 kDa, contained sugars that bound to concanavalin A and ricin. The jacob gene encoded a 45-kDa protein with a ladder-like series of five Cys-rich domains. These Cys-rich domains were reminiscent of but not homologous to the Cys-rich chitin-binding domains of insect chitinases and peritrophic matrix proteins that surround the food bolus in the insect gut. Jacob bound purified chitin and chitin remaining in sodium dodecyl sulfate-treated cyst walls. Conversely, the E. histolytica plasma membrane Gal/GalNAc lectin bound sugars of intact cyst walls and purified Jacob. In the presence of galactose, E. invadens formed wall-less cysts, which were quadranucleate and contained Jacob and chitinase (another encystation-specific protein) in secretory vesicles. A galactose lectin was found to be present on the surface of wall-less cysts, which phagocytosed bacteria and mucin-coated beads. These results suggest that the E. invadens cyst wall forms when the plasma membrane galactose lectin binds sugars on Jacob, which in turn binds chitin via its five chitin-binding domains. PMID:10858239

  3. The secondary cell wall polysaccharide of Bacillus anthracis provides the specific binding ligand for the C-terminal cell wall-binding domain of two phage endolysins, PlyL and PlyG

    PubMed Central

    Ganguly, Jhuma; Low, Lieh Y; Kamal, Nazia; Saile, Elke; Forsberg, L Scott; Gutierrez-Sanchez, Gerardo; Hoffmaster, Alex R; Liddington, Robert; Quinn, Conrad P; Carlson, Russell W; Kannenberg, Elmar L

    2013-01-01

    Endolysins are bacteriophage enzymes that lyse their bacterial host for phage progeny release. They commonly contain an N-terminal catalytic domain that hydrolyzes bacterial peptidoglycan (PG) and a C-terminal cell wall-binding domain (CBD) that confers enzyme localization to the PG substrate. Two endolysins, phage lysin L (PlyL) and phage lysin G (PlyG), are specific for Bacillus anthracis. To date, the cell wall ligands for their C-terminal CBD have not been identified. We recently described structures for a number of secondary cell wall polysaccharides (SCWPs) from B. anthracis and B. cereus strains. They are covalently bound to the PG and are comprised of a -ManNAc-GlcNAc-HexNAc- backbone with various galactosyl or glucosyl substitutions. Surface plasmon resonance (SPR) showed that the endolysins PlyL and PlyG bind to the SCWP from B. anthracis (SCWPBa) with high affinity (i.e. in the μM range with dissociation constants ranging from 0.81 × 10−6 to 7.51 × 10−6 M). In addition, the PlyL and PlyG SCWPBa binding sites reside with their C-terminal domains. The dissociation constants for the interactions of these endolysins and their derived C-terminal domains with the SCWPBa were in the range reported for other protein–carbohydrate interactions. Our findings show that the SCWPBa is the ligand that confers PlyL and PlyG lysin binding and localization to the PG. PlyL and PlyG also bound the SCWP from B. cereus G9241 with comparable affinities to SCWPBa. No detectable binding was found to the SCWPs from B. cereus ATCC (American Type Culture Collection) 10987 and ATCC 14579, thus demonstrating specificity of lysin binding to SCWPs. PMID:23493680

  4. Domain wall nanoelectronics

    NASA Astrophysics Data System (ADS)

    Catalan, G.; Seidel, J.; Ramesh, R.; Scott, J. F.

    2012-01-01

    Domains in ferroelectrics were considered to be well understood by the middle of the last century: They were generally rectilinear, and their walls were Ising-like. Their simplicity stood in stark contrast to the more complex Bloch walls or Néel walls in magnets. Only within the past decade and with the introduction of atomic-resolution studies via transmission electron microscopy, electron holography, and atomic force microscopy with polarization sensitivity has their real complexity been revealed. Additional phenomena appear in recent studies, especially of magnetoelectric materials, where functional properties inside domain walls are being directly measured. In this paper these studies are reviewed, focusing attention on ferroelectrics and multiferroics but making comparisons where possible with magnetic domains and domain walls. An important part of this review will concern device applications, with the spotlight on a new paradigm of ferroic devices where the domain walls, rather than the domains, are the active element. Here magnetic wall microelectronics is already in full swing, owing largely to the work of Cowburn and of Parkin and their colleagues. These devices exploit the high domain wall mobilities in magnets and their resulting high velocities, which can be supersonic, as shown by Kreines’ and co-workers 30 years ago. By comparison, nanoelectronic devices employing ferroelectric domain walls often have slower domain wall speeds, but may exploit their smaller size as well as their different functional properties. These include domain wall conductivity (metallic or even superconducting in bulk insulating or semiconducting oxides) and the fact that domain walls can be ferromagnetic while the surrounding domains are not.

  5. Skyrmion domain wall collision and domain wall-gated skyrmion logic

    NASA Astrophysics Data System (ADS)

    Xing, Xiangjun; Pong, Philip W. T.; Zhou, Yan

    2016-08-01

    Skyrmions and domain walls are significant spin textures of great technological relevance to magnetic memory and logic applications, where they can be used as carriers of information. The unique topology of skyrmions makes them display emergent dynamical properties as compared with domain walls. Some studies have demonstrated that the two topologically inequivalent magnetic objects could be interconverted by using cleverly designed geometric structures. Here, we numerically address the skyrmion domain wall collision in a magnetic racetrack by introducing relative motion between the two objects based on a specially designed junction. An electric current serves as the driving force that moves a skyrmion toward a trapped domain wall pair. We see different types of collision dynamics depending on the driving parameters. Most importantly, the modulation of skyrmion transport using domain walls is realized in this system, allowing a set of domain wall-gated logical NOT, NAND, and NOR gates to be constructed. This work provides a skyrmion-based spin-logic architecture that is fully compatible with racetrack memories.

  6. The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division.

    PubMed

    Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S

    2017-07-15

    Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.

  7. PREFACE: Domain wall dynamics in nanostructures Domain wall dynamics in nanostructures

    NASA Astrophysics Data System (ADS)

    Marrows, C. H.; Meier, G.

    2012-01-01

    Domain structures in magnetic materials are ubiquitous and have been studied for decades. The walls that separate them are topological defects in the magnetic order parameter and have a wide variety of complex forms. In general, their investigation is difficult in bulk materials since only the domain structure on the surface of a specimen is visible. Cutting the sample to reveal the interior causes a rearrangement of the domains into a new form. As with many other areas of magnetism, the study of domain wall physics has been revitalised by the advent of nanotechnology. The ability to fabricate nanoscale structures has permitted the formation of simplified and controlled domain patterns; the development of advanced microscopy methods has permitted them to be imaged and then modelled; subjecting them to ultrashort field and current pulses has permitted their dynamics to be explored. The latest results from all of these advances are described in this special issue. Not only has this led to results of great scientific beauty, but also to concepts of great applicability to future information technologies. In this issue the reader will find the latest results for these domain wall dynamics and the high-speed processes of topological structures such as domain walls and magnetic vortices. These dynamics can be driven by the application of magnetic fields, or by flowing currents through spintronic devices using the novel physics of spin-transfer torque. This complexity has been studied using a wide variety of experimental techniques at the edge of the spatial and temporal resolution currently available, and can be described using sophisticated analytical theory and computational modelling. As a result, the dynamics can be engineered to give rise to finely controlled memory and logic devices with new functionality. Moreover, the field is moving to study not only the conventional transition metal ferromagnets, but also complex heterostructures, novel magnets and even other

  8. Cross-Linked Peptidoglycan Mediates Lysostaphin Binding to the Cell Wall Envelope of Staphylococcus aureus†

    PubMed Central

    Gründling, Angelika; Schneewind, Olaf

    2006-01-01

    Staphylococcus simulans bv. staphylolyticus secretes lysostaphin, a bacteriocin that cleaves pentaglycine cross bridges in the cell wall of Staphylococcus aureus. The C-terminal cell wall-targeting domain (CWT) of lysostaphin is required for selective binding of this bacteriocin to S. aureus cells; however, the molecular target for this was unknown. We used purified green fluorescent protein fused to CWT (GFP-CWT) to reveal species-specific association of the reporter with staphylococci. GFP-CWT bound S. aureus cells as well as purified peptidoglycan sacculi. The addition of cross-linked murein, disaccharides linked to interconnected wall peptides, blocked GFP-CWT binding to staphylococci, whereas murein monomers or lysostaphin-solubilized cell wall fragments did not. S. aureus strain Newman variants lacking the capacity for synthesizing polysaccharide capsule (capFO), poly-N-acetylglucosamine (icaAC), lipoprotein (lgt), cell wall-anchored proteins (srtA), or the glycolipid anchor of lipoteichoic acid (ypfP) bound GFP-CWT similar to wild-type staphylococci. A tagO mutant strain, defective in the synthesis of polyribitol wall teichoic acid attached to the cell wall envelope, displayed increased GFP-CWT binding. In contrast, a femAB mutation, reducing both the amount and the length of peptidoglycan cross-linking (monoglycine cross bridges), showed a dramatic reduction in GFP-CWT binding. Thus, the CWT domain of lysostaphin directs the bacteriocin to cross-linked peptidoglycan, which also serves as the substrate for its glycyl-glycine endopeptidase domain. PMID:16547033

  9. Cross-linked peptidoglycan mediates lysostaphin binding to the cell wall envelope of Staphylococcus aureus.

    PubMed

    Gründling, Angelika; Schneewind, Olaf

    2006-04-01

    Staphylococcus simulans bv. staphylolyticus secretes lysostaphin, a bacteriocin that cleaves pentaglycine cross bridges in the cell wall of Staphylococcus aureus. The C-terminal cell wall-targeting domain (CWT) of lysostaphin is required for selective binding of this bacteriocin to S. aureus cells; however, the molecular target for this was unknown. We used purified green fluorescent protein fused to CWT (GFP-CWT) to reveal species-specific association of the reporter with staphylococci. GFP-CWT bound S. aureus cells as well as purified peptidoglycan sacculi. The addition of cross-linked murein, disaccharides linked to interconnected wall peptides, blocked GFP-CWT binding to staphylococci, whereas murein monomers or lysostaphin-solubilized cell wall fragments did not. S. aureus strain Newman variants lacking the capacity for synthesizing polysaccharide capsule (capFO), poly-N-acetylglucosamine (icaAC), lipoprotein (lgt), cell wall-anchored proteins (srtA), or the glycolipid anchor of lipoteichoic acid (ypfP) bound GFP-CWT similar to wild-type staphylococci. A tagO mutant strain, defective in the synthesis of polyribitol wall teichoic acid attached to the cell wall envelope, displayed increased GFP-CWT binding. In contrast, a femAB mutation, reducing both the amount and the length of peptidoglycan cross-linking (monoglycine cross bridges), showed a dramatic reduction in GFP-CWT binding. Thus, the CWT domain of lysostaphin directs the bacteriocin to cross-linked peptidoglycan, which also serves as the substrate for its glycyl-glycine endopeptidase domain.

  10. Topological domain walls in helimagnets

    NASA Astrophysics Data System (ADS)

    Schoenherr, P.; Müller, J.; Köhler, L.; Rosch, A.; Kanazawa, N.; Tokura, Y.; Garst, M.; Meier, D.

    2018-05-01

    Domain walls naturally arise whenever a symmetry is spontaneously broken. They interconnect regions with different realizations of the broken symmetry, promoting structure formation from cosmological length scales to the atomic level1,2. In ferroelectric and ferromagnetic materials, domain walls with unique functionalities emerge, holding great promise for nanoelectronics and spintronics applications3-5. These walls are usually of Ising, Bloch or Néel type and separate homogeneously ordered domains. Here we demonstrate that a wide variety of new domain walls occurs in the presence of spatially modulated domain states. Using magnetic force microscopy and micromagnetic simulations, we show three fundamental classes of domain walls to arise in the near-room-temperature helimagnet iron germanium. In contrast to conventional ferroics, the domain walls exhibit a well-defined inner structure, which—analogous to cholesteric liquid crystals—consists of topological disclination and dislocation defects. Similar to the magnetic skyrmions that form in the same material6,7, the domain walls can carry a finite topological charge, permitting an efficient coupling to spin currents and contributions to a topological Hall effect. Our study establishes a new family of magnetic nano-objects with non-trivial topology, opening the door to innovative device concepts based on helimagnetic domain walls.

  11. Polarization domain walls in optical fibres as topological bits for data transmission

    PubMed Central

    Gilles, M.; Bony, P-Y.; Garnier, J.; Picozzi, A.; Guasoni, M.; Fatome, J.

    2016-01-01

    Domain walls are topological defects which occur at symmetry-breaking phase transitions. While domain walls have been intensively studied in ferromagnetic materials, where they nucleate at the boundary of neighbouring regions of oppositely aligned magnetic dipoles, their equivalent in optics have not been fully explored so far. Here, we experimentally demonstrate the existence of a universal class of polarization domain walls in the form of localized polarization knots in conventional optical fibres. We exploit their binding properties for optical data transmission beyond the Kerr limits of normally dispersive fibres. In particular, we demonstrate how trapping energy in well-defined train of polarization domain walls allows undistorted propagation of polarization knots at a rate of 28 GHz along a 10 km length of normally dispersive optical fibre. These results constitute the first experimental observation of kink-antikink solitary wave propagation in nonlinear fibre optics. PMID:28168000

  12. Visualizing domain wall and reverse domain superconductivity.

    PubMed

    Iavarone, M; Moore, S A; Fedor, J; Ciocys, S T; Karapetrov, G; Pearson, J; Novosad, V; Bader, S D

    2014-08-28

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application.

  13. Visualizing domain wall and reverse domain superconductivity

    PubMed Central

    Iavarone, M.; Moore, S. A.; Fedor, J.; Ciocys, S. T.; Karapetrov, G.; Pearson, J.; Novosad, V.; Bader, S. D.

    2014-01-01

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application. PMID:25164004

  14. A small cellulose binding domain protein (CBD1) is highly variable in the nonbinding amino terminus

    USDA-ARS?s Scientific Manuscript database

    The small cellulose binding domain protein CBD1 is tightly bound to the cellulosic cell wall of the plant pathogenic stramenophile Phytophthora infestans. Transgene expression of the protein in plants has also demonstrated binding to plant cell walls. A study was undertaken using 47 isolates of P. ...

  15. Skyrmions from Instantons inside Domain Walls

    NASA Astrophysics Data System (ADS)

    Eto, Minoru; Nitta, Muneto; Ohashi, Keisuke; Tong, David

    2005-12-01

    Some years ago, Atiyah and Manton described a method to construct approximate Skyrmion solutions from Yang-Mills instantons. Here we present a dynamical realization of this construction using domain walls in a five-dimensional gauge theory. The non-Abelian gauge symmetry is broken in each vacuum but restored in the core of the domain wall, allowing instantons to nestle inside the wall. We show that the world volume dynamics of the wall is given by the Skyrme model, including the four-derivative term, and the instantons appear as domain wall Skyrmions.

  16. Curvature-induced domain wall pinning

    NASA Astrophysics Data System (ADS)

    Yershov, Kostiantyn V.; Kravchuk, Volodymyr P.; Sheka, Denis D.; Gaididei, Yuri

    2015-09-01

    It is shown that a local bend of a nanowire is a source of pinning potential for a transversal head-to-head (tail-to-tail) domain wall. Eigenfrequency of the domain wall free oscillations at the pinning potential and the effective friction are determined as functions of the curvature and domain wall width. The pinning potential originates from the effective curvature-induced Dzyaloshinsky-like term in the exchange energy. The theoretical results are verified by means of micromagnetic simulations for the case of parabolic shape of the wire bend.

  17. Effective description of domain wall strings

    NASA Astrophysics Data System (ADS)

    Rodrigues, Davi R.; Abanov, Ar.; Sinova, J.; Everschor-Sitte, K.

    2018-04-01

    The analysis of domain wall dynamics is often simplified to one-dimensional physics. For domain walls in thin films, more realistic approaches require the description as two-dimensional objects. This includes the study of vortices and curvatures along the domain walls as well as the influence of boundary effects. Here we provide a theory in terms of soft modes that allows us to analytically study the physics of extended domain walls and their stability. By considering irregularly shaped skyrmions as closed domain walls, we analyze their plasticity and compare their dynamics with those of circular skyrmions. Our theory directly provides an analytical description of the excitation modes of magnetic skyrmions, previously accessible only through sophisticated micromagnetic numerical calculations and spectral analysis. These analytical expressions provide the scaling behavior of the different physics on parameters that experiments can test.

  18. Edge states in gated bilayer-monolayer graphene ribbons and bilayer domain walls

    NASA Astrophysics Data System (ADS)

    Mirzakhani, M.; Zarenia, M.; Peeters, F. M.

    2018-05-01

    Using the effective continuum model, the electron energy spectrum of gated bilayer graphene with a step-like region of decoupled graphene layers at the edge of the sample is studied. Different types of coupled-decoupled interfaces are considered, i.e., zigzag (ZZ) and armchair junctions, which result in significant different propagating states. Two non-valley-polarized conducting edge states are observed for ZZ type, which are mainly located around the ZZ-ended graphene layers. Additionally, we investigated both BA-BA and BA-AB domain walls in the gated bilayer graphene within the continuum approximation. Unlike the BA-BA domain wall, which exhibits gapped insulating behaviour, the domain walls surrounded by different stackings of bilayer regions feature valley-polarized edge states. Our findings are consistent with other theoretical calculations, such as from the tight-binding model and first-principles calculations, and agree with experimental observations.

  19. Insights into substrate specificity of NlpC/P60 cell wall hydrolases containing bacterial SH3 domains

    DOE PAGES

    Xu, Qingping; Mengin-Lecreulx, Dominique; Liu, Xueqian W.; ...

    2015-09-15

    Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. In addition, these enzymes all have γ-d-Glu-A 2pm (A 2pm is diaminopimelic acid) cysteine amidase (ordl-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminall-Ala. Their crystal structures revealed a highly conserved structuremore » consisting of two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation.Peptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural analysis of three modular NlpC/P60 hydrolases, one lysin, and two recycling enzymes

  20. Insights into substrate specificity of NlpC/P60 cell wall hydrolases containing bacterial SH3 domains

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

    Xu, Qingping; Mengin-Lecreulx, Dominique; Liu, Xueqian W.

    Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. In addition, these enzymes all have γ-d-Glu-A 2pm (A 2pm is diaminopimelic acid) cysteine amidase (ordl-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminall-Ala. Their crystal structures revealed a highly conserved structuremore » consisting of two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation.Peptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural analysis of three modular NlpC/P60 hydrolases, one lysin, and two recycling enzymes

  1. Insights into Substrate Specificity of NlpC/P60 Cell Wall Hydrolases Containing Bacterial SH3 Domains

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

    Xu, Qingping; Mengin-Lecreulx, Dominique; Liu, Xueqian W.

    ABSTRACT Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. These enzymes all have γ-d-Glu-A 2pm (A 2pm is diaminopimelic acid) cysteine amidase (ordl-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminall-Ala. Their crystal structures revealed a highly conserved structure consistingmore » of two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation. IMPORTANCEPeptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural analysis of three modular NlpC/P60 hydrolases, one lysin, and two recycling

  2. Robust ferromagnetism carried by antiferromagnetic domain walls

    NASA Astrophysics Data System (ADS)

    Hirose, Hishiro T.; Yamaura, Jun-Ichi; Hiroi, Zenji

    2017-02-01

    Ferroic materials, such as ferromagnetic or ferroelectric materials, have been utilized as recording media for memory devices. A recent trend for downsizing, however, requires an alternative, because ferroic orders tend to become unstable for miniaturization. The domain wall nanoelectronics is a new developing direction for next-generation devices, in which atomic domain walls, rather than conventional, large domains themselves, are the active elements. Here we show that atomically thin magnetic domain walls generated in the antiferromagnetic insulator Cd2Os2O7 carry unusual ferromagnetic moments perpendicular to the wall as well as electron conductivity: the ferromagnetic moments are easily polarized even by a tiny field of 1 mT at high temperature, while, once cooled down, they are surprisingly robust even in an inverse magnetic field of 7 T. Thus, the magnetic domain walls could serve as a new-type of microscopic, switchable and electrically readable magnetic medium which is potentially important for future applications in the domain wall nanoelectronics.

  3. Robust ferromagnetism carried by antiferromagnetic domain walls

    PubMed Central

    Hirose, Hishiro T.; Yamaura, Jun-ichi; Hiroi, Zenji

    2017-01-01

    Ferroic materials, such as ferromagnetic or ferroelectric materials, have been utilized as recording media for memory devices. A recent trend for downsizing, however, requires an alternative, because ferroic orders tend to become unstable for miniaturization. The domain wall nanoelectronics is a new developing direction for next-generation devices, in which atomic domain walls, rather than conventional, large domains themselves, are the active elements. Here we show that atomically thin magnetic domain walls generated in the antiferromagnetic insulator Cd2Os2O7 carry unusual ferromagnetic moments perpendicular to the wall as well as electron conductivity: the ferromagnetic moments are easily polarized even by a tiny field of 1 mT at high temperature, while, once cooled down, they are surprisingly robust even in an inverse magnetic field of 7 T. Thus, the magnetic domain walls could serve as a new-type of microscopic, switchable and electrically readable magnetic medium which is potentially important for future applications in the domain wall nanoelectronics. PMID:28195565

  4. Structure of the choline-binding domain of Spr1274 in Streptococcus pneumoniae.

    PubMed

    Zhang, Zhenyi; Li, Wenzhe; Frolet, Cecile; Bao, Rui; di Guilmi, Anne Marie; Vernet, Thierry; Chen, Yuxing

    2009-08-01

    Spr1274 is a putative choline-binding protein that is bound to the cell wall of Streptococcus pneumoniae through noncovalent interactions with the choline moieties of teichoic and lipoteichoic acids. Its function is still unknown. The crystal structure of the choline-binding domain of Spr1274 (residues 44-129) was solved at 2.38 A resolution with three molecules in the asymmetric unit. It may provide a structural basis for functional analysis of choline-binding proteins.

  5. Velocity Enhancement by Synchronization of Magnetic Domain Walls

    NASA Astrophysics Data System (ADS)

    Hrabec, Aleš; Křižáková, Viola; Pizzini, Stefania; Sampaio, João; Thiaville, André; Rohart, Stanislas; Vogel, Jan

    2018-06-01

    Magnetic domain walls are objects whose dynamics is inseparably connected to their structure. In this Letter, we investigate magnetic bilayers, which are engineered such that a coupled pair of domain walls, one in each layer, is stabilized by a cooperation of Dzyaloshinskii-Moriya interaction and flux-closing mechanism. The dipolar field mediating the interaction between the two domain walls links not only their position but also their structure. We show that this link has a direct impact on their magnetic-field-induced dynamics. We demonstrate that in such a system the coupling leads to an increased domain wall velocity with respect to single domain walls. Since the domain wall dynamics is observed in a precessional regime, the dynamics involves the synchronization between the two walls to preserve the flux closure during motion. Properties of these coupled oscillating walls can be tuned by an additional in-plane magnetic field enabling a rich variety of states, from perfect synchronization to complete detuning.

  6. Magnetization reversal in ferromagnetic spirals via domain wall motion

    NASA Astrophysics Data System (ADS)

    Schumm, Ryan D.; Kunz, Andrew

    2016-11-01

    Domain wall dynamics have been investigated in a variety of ferromagnetic nanostructures for potential applications in logic, sensing, and recording. We present a combination of analytic and simulated results describing the reliable field driven motion of a domain wall through the arms of a ferromagnetic spiral nanowire. The spiral geometry is capable of taking advantage of the benefits of both straight and circular wires. Measurements of the in-plane components of the spirals' magnetization can be used to determine the angular location of the domain wall, impacting the magnetoresistive applications dependent on the domain wall location. The spirals' magnetization components are found to depend on the spiral parameters: the initial radius and spacing between spiral arms, along with the domain wall location. The magnetization is independent of the parameters of the rotating field used to move the domain wall, and therefore the model is valid for current induced domain wall motion as well. The speed of the domain wall is found to depend on the frequency of the rotating driving field, and the domain wall speeds can be reliably varied over several orders of magnitude. We further demonstrate a technique capable of injecting multiple domain walls and show the reliable and unidirectional motion of domain walls through the arms of the spiral.

  7. The formation and evolution of domain walls

    NASA Technical Reports Server (NTRS)

    Press, William H.; Ryden, Barbara S.; Spergel, David N.

    1991-01-01

    Domain walls are sheet-like defects produced when the low energy vacuum has isolated degenerate minima. The researchers' computer code follows the evolution of a scalar field, whose dynamics are determined by its Lagrangian density. The topology of the scalar field determines the evolution of the domain walls. This approach treats both wall dynamics and reconnection. The researchers investigated not only potentials that produce single domain walls, but also potentials that produce a network of walls and strings. These networks arise in axion models where the U(1) Peccei-Quinn symmetry is broken into Z sub N discrete symmetries. If N equals 1, the walls are bounded by strings and the network quickly disappears. For N greater than 1, the network of walls and strings behaved qualitatively just as the wall network shown in the figures given here. This both confirms the researchers' pessimistic view that domain walls cannot play an important role in the formation of large scale structure and implies that axion models with multiple minimum can be cosmologically disastrous.

  8. Functional electronic inversion layers at ferroelectric domain walls

    NASA Astrophysics Data System (ADS)

    Mundy, J. A.; Schaab, J.; Kumagai, Y.; Cano, A.; Stengel, M.; Krug, I. P.; Gottlob, D. M.; Doğanay, H.; Holtz, M. E.; Held, R.; Yan, Z.; Bourret, E.; Schneider, C. M.; Schlom, D. G.; Muller, D. A.; Ramesh, R.; Spaldin, N. A.; Meier, D.

    2017-06-01

    Ferroelectric domain walls hold great promise as functional two-dimensional materials because of their unusual electronic properties. Particularly intriguing are the so-called charged walls where a polarity mismatch causes local, diverging electrostatic potentials requiring charge compensation and hence a change in the electronic structure. These walls can exhibit significantly enhanced conductivity and serve as a circuit path. The development of all-domain-wall devices, however, also requires walls with controllable output to emulate electronic nano-components such as diodes and transistors. Here we demonstrate electric-field control of the electronic transport at ferroelectric domain walls. We reversibly switch from resistive to conductive behaviour at charged walls in semiconducting ErMnO3. We relate the transition to the formation--and eventual activation--of an inversion layer that acts as the channel for the charge transport. The findings provide new insight into the domain-wall physics in ferroelectrics and foreshadow the possibility to design elementary digital devices for all-domain-wall circuitry.

  9. Correlation between spin structure oscillations and domain wall velocities

    PubMed Central

    Bisig, André; Stärk, Martin; Mawass, Mohamad-Assaad; Moutafis, Christoforos; Rhensius, Jan; Heidler, Jakoba; Büttner, Felix; Noske, Matthias; Weigand, Markus; Eisebitt, Stefan; Tyliszczak, Tolek; Van Waeyenberge, Bartel; Stoll, Hermann; Schütz, Gisela; Kläui, Mathias

    2013-01-01

    Magnetic sensing and logic devices based on the motion of magnetic domain walls rely on the precise and deterministic control of the position and the velocity of individual magnetic domain walls in curved nanowires. Varying domain wall velocities have been predicted to result from intrinsic effects such as oscillating domain wall spin structure transformations and extrinsic pinning due to imperfections. Here we use direct dynamic imaging of the nanoscale spin structure that allows us for the first time to directly check these predictions. We find a new regime of oscillating domain wall motion even below the Walker breakdown correlated with periodic spin structure changes. We show that the extrinsic pinning from imperfections in the nanowire only affects slow domain walls and we identify the magnetostatic energy, which scales with the domain wall velocity, as the energy reservoir for the domain wall to overcome the local pinning potential landscape. PMID:23978905

  10. Tunable inertia of chiral magnetic domain walls

    PubMed Central

    Torrejon, Jacob; Martinez, Eduardo; Hayashi, Masamitsu

    2016-01-01

    The time it takes to accelerate an object from zero to a given velocity depends on the applied force and the environment. If the force ceases, it takes exactly the same time to completely decelerate. A magnetic domain wall is a topological object that has been observed to follow this behaviour. Here we show that acceleration and deceleration times of chiral Neel walls driven by current are different in a system with low damping and moderate Dzyaloshinskii–Moriya exchange constant. The time needed to accelerate a domain wall with current via the spin Hall torque is much faster than the time it needs to decelerate once the current is turned off. The deceleration time is defined by the Dzyaloshinskii–Moriya exchange constant whereas the acceleration time depends on the spin Hall torque, enabling tunable inertia of chiral domain walls. Such unique feature of chiral domain walls can be utilized to move and position domain walls with lower current, key to the development of storage class memory devices. PMID:27882932

  11. Geometrical Dependence of Domain-Wall Propagation and Nucleation Fields in Magnetic-Domain-Wall Sensors

    NASA Astrophysics Data System (ADS)

    Borie, B.; Kehlberger, A.; Wahrhusen, J.; Grimm, H.; Kläui, M.

    2017-08-01

    We study the key domain-wall properties in segmented nanowire loop-based structures used in domain-wall-based sensors. The two reasons for device failure, namely, distribution of the domain-wall propagation field (depinning) and the nucleation field are determined with magneto-optical Kerr effect and giant-magnetoresistance (GMR) measurements for thousands of elements to obtain significant statistics. Single layers of Ni81 Fe19 , a complete GMR stack with Co90 Fe10 /Ni81Fe19 as a free layer, and a single layer of Co90 Fe10 are deposited and industrially patterned to determine the influence of the shape anisotropy, the magnetocrystalline anisotropy, and the fabrication processes. We show that the propagation field is influenced only slightly by the geometry but significantly by material parameters. Simulations for a realistic wire shape yield a curling-mode type of magnetization configuration close to the nucleation field. Nonetheless, we find that the domain-wall nucleation fields can be described by a typical Stoner-Wohlfarth model related to the measured geometrical parameters of the wires and fitted by considering the process parameters. The GMR effect is subsequently measured in a substantial number of devices (3000) in order to accurately gauge the variation between devices. This measurement scheme reveals a corrected upper limit to the nucleation fields of the sensors that can be exploited for fast characterization of the working elements.

  12. Axion domain wall baryogenesis

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

    Daido, Ryuji; Kitajima, Naoya; Takahashi, Fuminobu, E-mail: daido@tuhep.phys.tohoku.ac.jp, E-mail: kitajima@tuhep.phys.tohoku.ac.jp, E-mail: fumi@tuhep.phys.tohoku.ac.jp

    2015-07-01

    We propose a new scenario of baryogenesis, in which annihilation of axion domain walls generates a sizable baryon asymmetry. Successful baryogenesis is possible for a wide range of the axion mass and decay constant, m ≅ 10{sup 8}–10{sup 13} GeV and f ≅ 10{sup 13}–10{sup 16} GeV . Baryonic isocurvature perturbations are significantly suppressed in our model, in contrast to various spontaneous baryogenesis scenarios in the slow-roll regime. In particular, the axion domain wall baryogenesis is consistent with high-scale inflation which generates a large tensor-to-scalar ratio within the reach of future CMB B-mode experiments. We also discuss the gravitational waves produced by the domainmore » wall annihilation and its implications for the future gravitational wave experiments.« less

  13. Temporary formation of highly conducting domain walls for non-destructive read-out of ferroelectric domain-wall resistance switching memories

    NASA Astrophysics Data System (ADS)

    Jiang, Jun; Bai, Zi Long; Chen, Zhi Hui; He, Long; Zhang, David Wei; Zhang, Qing Hua; Shi, Jin An; Park, Min Hyuk; Scott, James F.; Hwang, Cheol Seong; Jiang, An Quan

    2018-01-01

    Erasable conductive domain walls in insulating ferroelectric thin films can be used for non-destructive electrical read-out of the polarization states in ferroelectric memories. Still, the domain-wall currents extracted by these devices have not yet reached the intensity and stability required to drive read-out circuits operating at high speeds. This study demonstrated non-destructive read-out of digital data stored using specific domain-wall configurations in epitaxial BiFeO3 thin films formed in mesa-geometry structures. Partially switched domains, which enable the formation of conductive walls during the read operation, spontaneously retract when the read voltage is removed, reducing the accumulation of mobile defects at the domain walls and potentially improving the device stability. Three-terminal memory devices produced 14 nA read currents at an operating voltage of 5 V, and operated up to T = 85 °C. The gap length can also be smaller than the film thickness, allowing the realization of ferroelectric memories with device dimensions far below 100 nm.

  14. Domain walls in single-chain magnets

    NASA Astrophysics Data System (ADS)

    Pianet, Vivien; Urdampilleta, Matias; Colin, Thierry; Clérac, Rodolphe; Coulon, Claude

    2017-12-01

    The topology and creation energy of domain walls in different magnetic chains (called Single-Chain Magnets or SCMs) are discussed. As these domain walls, that can be seen as "defects", are known to control both static and dynamic properties of these one-dimensional systems, their study and understanding are necessary first steps before a deeper discussion of the SCM properties at finite temperature. The starting point of the paper is the simple regular ferromagnetic chain for which the characteristics of the domain walls are well known. Then two cases will be discussed (i) the "mixed chains" in which isotropic and anisotropic classical spins alternate, and (ii) the so-called "canted chains" where two different easy axis directions are present. In particular, we show that "strictly narrow" domain walls no longer exist in these more complex cases, while a cascade of phase transitions is found for canted chains as the canting angle approaches 45∘. The consequence for thermodynamic properties is briefly discussed in the last part of the paper.

  15. Ferroelectric domain wall motion induced by polarized light

    PubMed Central

    Rubio-Marcos, Fernando; Del Campo, Adolfo; Marchet, Pascal; Fernández, Jose F.

    2015-01-01

    Ferroelectric materials exhibit spontaneous and stable polarization, which can usually be reoriented by an applied external electric field. The electrically switchable nature of this polarization is at the core of various ferroelectric devices. The motion of the associated domain walls provides the basis for ferroelectric memory, in which the storage of data bits is achieved by driving domain walls that separate regions with different polarization directions. Here we show the surprising ability to move ferroelectric domain walls of a BaTiO3 single crystal by varying the polarization angle of a coherent light source. This unexpected coupling between polarized light and ferroelectric polarization modifies the stress induced in the BaTiO3 at the domain wall, which is observed using in situ confocal Raman spectroscopy. This effect potentially leads to the non-contact remote control of ferroelectric domain walls by light. PMID:25779918

  16. Domain wall conductivity in KTiOPO4 crystals

    NASA Astrophysics Data System (ADS)

    Lindgren, G.; Canalias, C.

    2017-07-01

    We study the local ionic conductivity of ferroelectric domain walls and domains in KTiOPO4 single-crystals. We show a fourfold increase in conductivity at the domain walls, compared to that of the domains, attributed to an increased concentration of defects. Our current-voltage measurements reveal memristive-like behavior associated with topographic changes and permanent charge displacement. This behavior is observed for all the voltage sweep-rates at the domain walls, while it only occurs for low frequencies at the domains. We attribute these findings to the redistribution of ions due to the applied bias and their effect on the tip-sample barrier.

  17. Domain wall remote pinning in magnetic nano wires

    NASA Astrophysics Data System (ADS)

    Read, Dan; Miguel, Jorge; Maccherozzi, Francesco; Cavill, Stuart; Dhesi, Sarnjeet; Cardiff University Collaboration; Diamond Light Source Collaboration

    2013-03-01

    In the current race for information storage media with ever increasing density the position of magnetic domain walls, the region in a magnetic system where the local magnetization continually rotates its direction between adjacent magnetic domains, is one of the most promising routes for future storage media devices. Information storage requires ultrafast read-out and writing operations, but domain walls need to be pinned so that the information is safely stored in the long term. Here we investigate the use of remote magnetostatic charges to trap domain walls. By using X-ray photoelectron emission microscopy we have followed the position of domain walls of opposite charge being pinned or repelled by pinning potentials of increasing strength. Micromagnetic simulations show an excellent agreement with the experimental results. We demonstrate the attractive or repulsive character of the interaction between domain wall and trap depending upon the sign of their magnetic charges. These quasi-static experiments are the antecedent to ultrafast time-resolved XMCD-PEEM experiments where the spin-transfer torque effect will be studied dynamically by applying picosecond-long current pulses across the magnetic nanowire.

  18. Domain walls and ferroelectric reversal in corundum derivatives

    NASA Astrophysics Data System (ADS)

    Ye, Meng; Vanderbilt, David

    2017-01-01

    Domain walls are the topological defects that mediate polarization reversal in ferroelectrics, and they may exhibit quite different geometric and electronic structures compared to the bulk. Therefore, a detailed atomic-scale understanding of the static and dynamic properties of domain walls is of pressing interest. In this work, we use first-principles methods to study the structures of 180∘ domain walls, both in their relaxed state and along the ferroelectric reversal pathway, in ferroelectrics belonging to the family of corundum derivatives. Our calculations predict their orientation, formation energy, and migration energy and also identify important couplings between polarization, magnetization, and chirality at the domain walls. Finally, we point out a strong empirical correlation between the height of the domain-wall-mediated polarization reversal barrier and the local bonding environment of the mobile A cations as measured by bond-valence sums. Our results thus provide both theoretical and empirical guidance for future searches for ferroelectric candidates in materials of the corundum derivative family.

  19. Domain wall formation in late-time phase transitions

    NASA Technical Reports Server (NTRS)

    Kolb, Edward W.; Wang, Yun

    1992-01-01

    We examine domain wall formulation in late time phase transitions. We find that in the invisible axion domain wall phenomenon, thermal effects alone are insufficient to drive different parts of the disconnected vacuum manifold. This suggests that domain walls do not form unless either there is some supplemental (but perhaps not unreasonable) dynamics to localize the scalar field responsible for the phase transition to the low temperature maximum (to an extraordinary precision) before the onset of the phase transition, or there is some non-thermal mechanism to produce large fluctuations in the scalar field. The fact that domain wall production is not a robust prediction of late time transitions may suggest future directions in model building.

  20. Domain walls and ferroelectric reversal in corundum derivatives

    NASA Astrophysics Data System (ADS)

    Ye, Meng; Vanderbilt, David

    Domain walls are the topological defects that mediate polarization reversal in ferroelectrics, and they may exhibit quite different geometric and electronic structures compared to the bulk. Therefore, a detailed atomic-scale understanding of the static and dynamic properties of domain walls is of pressing interest. In this work, we use first-principles methods to study the structures of 180° domain walls, both in their relaxed state and along the ferroelectric reversal pathway, in ferroelectrics belonging to the family of corundum derivatives. Our calculations predict their orientation, formation energy, and migration energy, and also identify important couplings between polarization, magnetization, and chirality at the domain walls. Finally, we point out a strong empirical correlation between the height of the domain-wall mediated polarization reversal barrier and the local bonding environment of the mobile A cations as measured by bond valence sums. Our results thus provide both theoretical and empirical guidance to further search for ferroelectric candidates in materials of the corundum derivative family. The work is supported by ONR Grant N00014-12-1-1035.

  1. Field enhancement of electronic conductance at ferroelectric domain walls

    DOE PAGES

    Vasudevan, Rama K.; Cao, Ye; Laanait, Nouamane; ...

    2017-11-06

    Ferroelectric domain walls have continued to attract widespread attention due to both the novelty of the phenomena observed and the ability to reliably pattern them in nanoscale dimensions. But, the conductivity mechanisms remain in debate, particularly around nominally uncharged walls. Here, we posit a conduction mechanism relying on field-modification effect from polarization re-orientation and the structure of the reverse-domain nucleus. Through conductive atomic force microscopy measurements on an ultra-thin (001) BiFeO 3 thin film, in combination with phase-field simulations, we show that the field-induced twisted domain nucleus formed at domain walls results in local-field enhancement around the region of themore » atomic force microscope tip. In conjunction with slight barrier lowering, these two effects are sufficient to explain the observed emission current distribution. Our results suggest that different electronic properties at domain walls are not necessary to observe localized enhancement in domain wall currents.« less

  2. Investigation of Ferroelectric Domain Walls by Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Stone, Gregory A.

    Ferroelectric materials are characterized by an intrinsic spontaneous electric dipole moment that can be manipulated by the application of an electric field. Regions inside the crystal, known as domains, can have the spontaneous dipole moments oriented in a different direction than the surrounding crystal. Due to favorable piezoelectric, pyroelectric, electro-optic, and nonlinear optical properties, ferroelectric materials are attractive for commercial applications. Many devices, such as nonlinear frequency converters, require precisely engineered domain patterns. The properties of domains and their boundaries, known as domain walls, are vital to the performance and limitations of these devices. As a result, ferroelectric domains and the domain walls have been the focus of many scientific studies. Despite all this work, questions remain regarding their properties. This work is aimed at developing a better understanding of the properties of the domain wall using confocal Raman spectroscopy. Raman spectra taken from domain walls in Lithium Niobate and Lithium Tantalate reveal two distinct changes in the Raman spectra: (1) Shifts in frequency of the bulk Raman modes, which persists over a range of 0.2-0.5 mu m from the domain wall. The absence of this effect in defect free stoichiometric Lithium Tantalate indicates that the shifts are related to defects inside the crystal. (2) The presence of Raman modes corresponding to phonons propagating orthogonal to the laser beam axis, which are not collected in the bulk crystal. The phonons also preferential propagate normal to the domain wall. These modes are detected up to 0.35 mum from the domain wall. The observation and separation of these effects was made possible by the optimized spatial resolution (0.23 mum) of a home-built scanning confocal microscope and the fact that degeneracy of the transverse and longitudinal phonon polarization is lifted by polar phonons in Lithium Niobate and Lithium Tantalate. Raman

  3. Domain walls in the extensions of the Standard Model

    NASA Astrophysics Data System (ADS)

    Krajewski, Tomasz; Lalak, Zygmunt; Lewicki, Marek; Olszewski, Paweł

    2018-05-01

    Our main interest is the evolution of domain walls of the Higgs field in the early Universe. The aim of this paper is to understand how dynamics of Higgs domain walls could be influenced by yet unknown interactions from beyond the Standard Model. We assume that the Standard Model is valid up to certain, high, energy scale Λ and use the framework of the effective field theory to describe physics below that scale. Performing numerical simulations with different values of the scale Λ we are able to extend our previous analysis [1]. Our recent numerical simulations show that evolution of Higgs domain walls is rather insensitive to interactions beyond the Standard Model as long as masses of new particles are grater than 1012 GeV. For lower values of Λ the RG improved effective potential is strongly modified at field strengths crucial to the evolution of domain walls. However, we find that even for low values of Λ, Higgs domain walls decayed shortly after their formation for generic initial conditions. On the other hand, in simulations with specifically chosen initial conditions Higgs domain walls can live longer and enter the scaling regime. We also determine the energy spectrum of gravitational waves produced by decaying domain walls of the Higgs field. For generic initial field configurations the amplitude of the signal is too small to be observed in planned detectors.

  4. Resonant tunneling across a ferroelectric domain wall

    NASA Astrophysics Data System (ADS)

    Li, M.; Tao, L. L.; Velev, J. P.; Tsymbal, E. Y.

    2018-04-01

    Motivated by recent experimental observations, we explore electron transport properties of a ferroelectric tunnel junction (FTJ) with an embedded head-to-head ferroelectric domain wall, using first-principles density-functional theory calculations. We consider a FTJ with L a0.5S r0.5Mn O3 electrodes separated by a BaTi O3 barrier layer and show that an in-plane charged domain wall in the ferroelectric BaTi O3 can be induced by polar interfaces. The resulting V -shaped electrostatic potential profile across the BaTi O3 layer creates a quantum well and leads to the formation of a two-dimensional electron gas, which stabilizes the domain wall. The confined electronic states in the barrier are responsible for resonant tunneling as is evident from our quantum-transport calculations. We find that the resonant tunneling is an orbital selective process, which leads to sharp spikes in the momentum- and energy-resolved transmission spectra. Our results indicate that domain walls embedded in FTJs can be used to control the electron transport.

  5. Phase transition solutions in geometrically constrained magnetic domain wall models

    NASA Astrophysics Data System (ADS)

    Chen, Shouxin; Yang, Yisong

    2010-02-01

    Recent work on magnetic phase transition in nanoscale systems indicates that new physical phenomena, in particular, the Bloch wall width narrowing, arise as a consequence of geometrical confinement of magnetization and leads to the introduction of geometrically constrained domain wall models. In this paper, we present a systematic mathematical analysis on the existence of the solutions of the basic governing equations in such domain wall models. We show that, when the cross section of the geometric constriction is a simple step function, the solutions may be obtained by minimizing the domain wall energy over the constriction and solving the Bogomol'nyi equation outside the constriction. When the cross section and potential density are both even, we establish the existence of an odd domain wall solution realizing the phase transition process between two adjacent domain phases. When the cross section satisfies a certain integrability condition, we prove that a domain wall solution always exists which links two arbitrarily designated domain phases.

  6. On thick domain walls in general relativity

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Noetzold, Dirk

    1989-01-01

    Planar scalar field configurations in general relativity differ considerably from those in flat space. It is shown that static domain walls of finite thickness in curved space-time do not possess a reflection symmetry. At infinity, the space-time tends to the Taub vacuum on one side of the wall and to the Minkowski vacuum (Rindler space-time) on the other. Massive test particles are always accelerated towards the Minkowski side, i.e., domain walls are attractive on the Taub side, but repulsive on the Minkowski side (Taub-vacuum cleaner). It is also proved that the pressure in all directions is always negative. Finally, a brief comment is made concerning the possibility of infinite, i.e., bigger than horizon size, domain walls in our universe. All of the results are independent of the form of the potential V(phi) greater than or equal to 0 of the scalar field phi.

  7. Driving chiral domain walls in antiferromagnets using rotating magnetic fields

    NASA Astrophysics Data System (ADS)

    Pan, Keming; Xing, Lingdi; Yuan, H. Y.; Wang, Weiwei

    2018-05-01

    We show theoretically and numerically that an antiferromagnetic domain wall can be moved by a rotating magnetic field in the presence of Dzyaloshinskii-Moriya interaction (DMI). Two motion modes are found: rigid domain wall motion at low frequency (corresponding to the perfect frequency synchronization) and the oscillating motion at high frequency. In the full synchronized region, the steady velocity of the domain wall is universal, in the sense that it depends only on the frequency of the rotating field and the ratio between DMI strength and exchange constant. The domain wall velocity is independent of the Gilbert damping and the rotating field strength. Moreover, a rotating field in megahertz is sufficient to move the antiferromagnetic domain wall.

  8. Dispersive Stiffness of Dzyaloshinskii Domain Walls

    NASA Astrophysics Data System (ADS)

    Pellegren, J. P.; Lau, D.; Sokalski, V.

    2017-07-01

    It is well documented that subjecting perpendicular magnetic films that exhibit the interfacial Dzyaloshinskii-Moriya interaction to an in-plane magnetic field results in a domain wall (DW) energy σ , which is highly anisotropic with respect to the orientation of the DW in the film plane Θ . We demonstrate that this anisotropy has a profound impact on the elastic response of the DW as characterized by the surface stiffness σ ˜ (Θ )=σ (Θ )+σ''(Θ ) and evaluate its dependence on the length scale of deformation. The influence of stiffness on DW mobility in the creep regime is assessed, with analytic and numerical calculations showing trends in σ ˜ that better represent experimental measurements of domain wall velocity in magnetic thin films compared to σ alone. Our treatment provides experimental support for theoretical models of the mobility of anisotropic elastic manifolds and makes progress toward a more complete understanding of magnetic domain wall creep.

  9. Conduction at domain walls in oxide multiferroics

    NASA Astrophysics Data System (ADS)

    Seidel, J.; Martin, L. W.; He, Q.; Zhan, Q.; Chu, Y.-H.; Rother, A.; Hawkridge, M. E.; Maksymovych, P.; Yu, P.; Gajek, M.; Balke, N.; Kalinin, S. V.; Gemming, S.; Wang, F.; Catalan, G.; Scott, J. F.; Spaldin, N. A.; Orenstein, J.; Ramesh, R.

    2009-03-01

    Domain walls may play an important role in future electronic devices, given their small size as well as the fact that their location can be controlled. Here, we report the observation of room-temperature electronic conductivity at ferroelectric domain walls in the insulating multiferroic BiFeO3. The origin and nature of the observed conductivity are probed using a combination of conductive atomic force microscopy, high-resolution transmission electron microscopy and first-principles density functional computations. Our analyses indicate that the conductivity correlates with structurally driven changes in both the electrostatic potential and the local electronic structure, which shows a decrease in the bandgap at the domain wall. Additionally, we demonstrate the potential for device applications of such conducting nanoscale features.

  10. Conduction at domain walls in oxide multiferroics.

    PubMed

    Seidel, J; Martin, L W; He, Q; Zhan, Q; Chu, Y-H; Rother, A; Hawkridge, M E; Maksymovych, P; Yu, P; Gajek, M; Balke, N; Kalinin, S V; Gemming, S; Wang, F; Catalan, G; Scott, J F; Spaldin, N A; Orenstein, J; Ramesh, R

    2009-03-01

    Domain walls may play an important role in future electronic devices, given their small size as well as the fact that their location can be controlled. Here, we report the observation of room-temperature electronic conductivity at ferroelectric domain walls in the insulating multiferroic BiFeO(3). The origin and nature of the observed conductivity are probed using a combination of conductive atomic force microscopy, high-resolution transmission electron microscopy and first-principles density functional computations. Our analyses indicate that the conductivity correlates with structurally driven changes in both the electrostatic potential and the local electronic structure, which shows a decrease in the bandgap at the domain wall. Additionally, we demonstrate the potential for device applications of such conducting nanoscale features.

  11. MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.

    PubMed

    Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu

    2013-05-01

    The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.

  12. The N-Terminal Domain of the Flo1 Flocculation Protein from Saccharomyces cerevisiae Binds Specifically to Mannose Carbohydrates ▿

    PubMed Central

    Goossens, Katty V. Y.; Stassen, Catherine; Stals, Ingeborg; Donohue, Dagmara S.; Devreese, Bart; De Greve, Henri; Willaert, Ronnie G.

    2011-01-01

    Saccharomyces cerevisiae cells possess a remarkable capacity to adhere to other yeast cells, which is called flocculation. Flocculation is defined as the phenomenon wherein yeast cells adhere in clumps and sediment rapidly from the medium in which they are suspended. These cell-cell interactions are mediated by a class of specific cell wall proteins, called flocculins, that stick out of the cell walls of flocculent cells. The N-terminal part of the three-domain protein is responsible for carbohydrate binding. We studied the N-terminal domain of the Flo1 protein (N-Flo1p), which is the most important flocculin responsible for flocculation of yeast cells. It was shown that this domain is both O and N glycosylated and is structurally composed mainly of β-sheets. The binding of N-Flo1p to d-mannose, α-methyl-d-mannoside, various dimannoses, and mannan confirmed that the N-terminal domain of Flo1p is indeed responsible for the sugar-binding activity of the protein. Moreover, fluorescence spectroscopy data suggest that N-Flo1p contains two mannose carbohydrate binding sites with different affinities. The carbohydrate dissociation constants show that the affinity of N-Flo1p for mono- and dimannoses is in the millimolar range for the binding site with low affinity and in the micromolar range for the binding site with high affinity. The high-affinity binding site has a higher affinity for low-molecular-weight (low-MW) mannose carbohydrates and no affinity for mannan. However, mannan as well as low-MW mannose carbohydrates can bind to the low-affinity binding site. These results extend the cellular flocculation model on the molecular level. PMID:21076009

  13. Domain Wall Formation in Ferromagnetic Layers: An Ab Initio Study

    NASA Astrophysics Data System (ADS)

    Herper, Heike C.

    Domain walls are an inherent feature of ferromagnetic (FM) films consisting of layers with different magnetic orientations. Since FM films are used in electrical devices the question of the influence of domain walls on, e.g., the magnetoresistance has attracted much interest. Besides discussing the resistance contribution of domain walls, it is appropriate to study different types of domain walls and their energy of formation. The behaviour of domain walls is usually discussed within model calculations. In the present paper it is done within an ab initio Green's function technique for layered systems, i.e., the fully relativistic, spin-polarized screened Korringa-Kohn Rostoker method. Results are presented for fcc Co layers covered by two semi-infinite fcc Pt(001) bulk systems or by bulk fcc Co(001), respectively. The resistance, which is caused by the different types of domain walls is discussed within a Kubo-Greenwood approach considering Co(001)/Co24/Co(001) as an example.

  14. Magnetic domain wall conduits for single cell applications.

    PubMed

    Donolato, M; Torti, A; Kostesha, N; Deryabina, M; Sogne, E; Vavassori, P; Hansen, M F; Bertacco, R

    2011-09-07

    The ability to trap, manipulate and release single cells on a surface is important both for fundamental studies of cellular processes and for the development of novel lab-on-chip miniaturized tools for biological and medical applications. In this paper we demonstrate how magnetic domain walls generated in micro- and nano-structures fabricated on a chip surface can be used to handle single yeast cells labeled with magnetic beads. In detail, first we show that the proposed approach maintains the microorganism viable, as proven by monitoring the division of labeled yeast cells trapped by domain walls over 16 hours. Moreover, we demonstrate the controlled transport and release of individual yeast cells via displacement and annihilation of individual domain walls in micro- and nano-sized magnetic structures. These results pave the way to the implementation of magnetic devices based on domain walls technology in lab-on-chip systems devoted to accurate individual cell trapping and manipulation.

  15. Role of spin diffusion in current-induced domain wall motion for disordered ferromagnets

    NASA Astrophysics Data System (ADS)

    Akosa, Collins Ashu; Kim, Won-Seok; Bisig, André; Kläui, Mathias; Lee, Kyung-Jin; Manchon, Aurélien

    2015-03-01

    Current-induced spin transfer torque and magnetization dynamics in the presence of spin diffusion in disordered magnetic textures is studied theoretically. We demonstrate using tight-binding calculations that weak, spin-conserving impurity scattering dramatically enhances the nonadiabaticity. To further explore this mechanism, a phenomenological drift-diffusion model for incoherent spin transport is investigated. We show that incoherent spin diffusion indeed produces an additional spatially dependent torque of the form ˜∇2[m ×(u .∇ ) m ] +ξ ∇2[(u .∇ ) m ] , where m is the local magnetization direction, u is the direction of injected current, and ξ is a parameter characterizing the spin dynamics (precession, dephasing, and spin-flip). This torque, which scales as the inverse square of the domain wall width, only weakly enhances the longitudinal velocity of a transverse domain wall but significantly enhances the transverse velocity of vortex walls. The spatial-dependent spin transfer torque uncovered in this study is expected to have significant impact on the current-driven motion of abrupt two-dimensional textures such as vortices, skyrmions, and merons.

  16. Spin-wave-driven high-speed domain-wall motions in soft magnetic nanotubes

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

    Yang, Jaehak; Yoo, Myoung-Woo; Kim, Sang-Koog, E-mail: sangkoog@snu.ac.kr

    We report on a micromagnetic simulation study of interactions between propagating spin waves and a head-to-head domain wall in geometrically confined magnetic nanotubes. We found that incident spin waves of specific frequencies can lead to sufficiently high-speed (on the order of a few hundreds of m/s or higher) domain-wall motions in the same direction as that of the incident spin-waves. The domain-wall motions and their speed vary remarkably with the frequency and the amplitude of the incident spin-waves. High-speed domain-wall motions originate from the transfer torque of spin waves' linear momentum to the domain wall, through the partial or completemore » reflection of the incident spin waves from the domain wall. This work provides a fundamental understanding of the interaction of the spin waves with a domain wall in the magnetic nanotubes as well as a route to all-magnetic control of domain-wall motions in the magnetic nanoelements.« less

  17. Magnetic domain walls as reconfigurable spin-wave nano-channels

    NASA Astrophysics Data System (ADS)

    Wagner, Kai

    Research efforts to utilize spin waves as information carriers for wave based logic in micro- and nano-structured ferromagnetic materials have increased tremendously over the recent years. However, finding efficient means of tailoring and downscaling guided spin-wave propagation in two dimensions, while maintaining energy efficiency and reconfigurability, still remains a delicate challenge. Here we target these challenges by spin-wave transport inside nanometer-scaled potential wells formed along magnetic domain walls. For this, we investigate the magnetization dynamics of a rectangular-like element in a Landau state exhibiting a so called 180° Néel wall along its center. By microwave antennae the rf-excitation is constricted to one end of the domain wall and the spin-wave intensities are recorded by means of Brillouin-Light Scattering microscopy revealing channeled transport. Additional micromagnetic simulations with pulsed as well as cw-excitation are performed to yield further insight into this class of modes. We find several spin-wave modes quantized along the width of the domain wall yet with well defined wave vectors along the wall, exhibiting positive dispersion. In a final step, we demonstrate the flexibility of these spin-wave nano-channels based on domain walls. In contrast to wave guides realised by fixed geometries, domain walls can be easily manipulated. Here we utilize small external fields to control its position with nanometer precision over a micrometer range, while still enabling transport. Domain walls thus, open the perspective for reprogrammable and yet non-volatile spin-wave waveguides of nanometer width. Financial support by the Deutsche Forschungsgemeinschaft within project SCHU2922/1-1 is gratefully acknowledged.

  18. Excitations of interface pinned domain walls in constrained geometries

    NASA Astrophysics Data System (ADS)

    Martins, S. M. S. B.; Oliveira, L. L.; Rebouças, G. O. G.; Dantas, Ana L.; Carriço, A. S.

    2018-05-01

    We report a theoretical investigation of the equilibrium pattern and the spectra of head-to-head and Neel domain walls of flat Fe and Py stripes, exchange coupled with a vicinal antiferromagnetic substrate. We show that the domain wall excitation spectrum is tunable by the strength of the interface field. Furthermore, strong interface coupling favors localized wall excitations.

  19. Ferroelectricity of domain walls in rare earth iron garnet films.

    PubMed

    Popov, A I; Zvezdin, K A; Gareeva, Z V; Mazhitova, F A; Vakhitov, R M; Yumaguzin, A R; Zvezdin, A K

    2016-11-16

    In this paper, we report on electric polarization arising in a vicinity of Bloch-like domain walls in rare-earth iron garnet films. The domain walls generate an intrinsic magnetic field that breaks an antiferroelectric structure formed in the garnets due to an exchange interaction between rare earth and iron sublattices. We explore 180° domain walls whose formation is energetically preferable in the films with perpendicular magnetic anisotropy. Magnetic and electric structures of the 180° quasi-Bloch domain walls have been simulated at various relations between system parameters. Singlet, doublet ground states of rare earth ions and strongly anisotropic rare earth Ising ions have been considered. Our results show that electric polarization appears in rare earth garnet films at Bloch domain walls, and the maximum of magnetic inhomogeneity is not always linked to the maximum of electric polarization. A number of factors including the temperature, the state of the rare earth ion and the type of a wall influence magnetically induced electric polarization. We show that the value of polarization can be enhanced by the shrinking of the Bloch domain wall width, decreasing the temperature, and increasing the deviations of magnetization from the Bloch rotation that are regulated by impacts given by magnetic anisotropies of the films.

  20. Hawking radiation from a Reisner-Nordström domain wall

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

    Greenwood, Eric, E-mail: esg3@buffalo.edu

    2010-01-01

    We investigate the effect on the Hawking radiation given off during the time of collapse of a Reisner-Nordström domain wall. Using the functional Schrödinger formalism we are able to probe the time-dependent regime, which is out of the reach of the standard approximations like the Bogolyubov method. We calculate the occupation number of particles for a scalar field and complex scalar field. We demonstrate that the particles from the scalar field are unaffected by the charge of the Reisner-Nordström domain wall, as is expected since the scalar field doesn't carry any charge, which would couple to the charge of themore » Reisner-Nordström domain wall. Here the situation effectively reduces to the uncharged case, a spherically symmetric domain wall. To take the charge into account, we consider the complex scalar field which represents charged particles and anti-particles. Here investigate two different cases, first the non-extremal case and second the extremal case. In the non-extremal case we demonstrate that when the particle (anti-particle) carries charge opposite to that of the domain wall, the occupation number becomes suppressed during late times of the collapse. Therefore the dominate occupation number is when the particle (anti-particle) carries the same charge as the domain wall, as expected due to the Coulomb potential carried by the domain walls. In the extremal case we demonstrate that as time increases the temperature of the radiation decreases until when the domain wall reaches the horizon and the temperature then goes to zero. This is in agreement with the Hawking temperature for charged black holes.« less

  1. Textural domain walls in superfluid 3He-B

    NASA Astrophysics Data System (ADS)

    Mizushima, Takeshi

    Owing to the richness of symmetry, the superfluid 3He serves as a rich repository of topological quantum phenomena. This includes the emergence of surface Majorana fermions and their quantum mass acquisition at the topological critical point. Furthermore, the marriage of the prototype topological superfluid with nanofabrication techniques brings about a rich variety of spontaneous symmetry breaking, such as the formation of the stripe order and nontrivial domain walls. In this work, we examine the possible formation of textural domain walls in the superfluid 3He-B confined to a thin slab with a sub-micron thickness. When an applied magnetic field is much higher than the dipolar field, two nearly degenerate ground states appear, which are characterized by the Ising order associated with the spontaneous breaking of a magnetic order-two symmetry, lcirc;z = + 1 and - 1 . We here discuss the structure of the textural domain wall formed by the spatial modulation of the Ising order, such as low-lying quasiparticle excitations and spontaneous spin current. We also report bosonic modes bound to the textural domain wall.

  2. Mechanistic insights into phosphoprotein-binding FHA domains.

    PubMed

    Liang, Xiangyang; Van Doren, Steven R

    2008-08-01

    [Structure: see text]. FHA domains are protein modules that switch signals in diverse biological pathways by monitoring the phosphorylation of threonine residues of target proteins. As part of the effort to gain insight into cellular avoidance of cancer, FHA domains involved in the cellular response to DNA damage have been especially well-characterized. The complete protein where the FHA domain resides and the interaction partners determine the nature of the signaling. Thus, a key biochemical question is how do FHA domains pick out their partners from among thousands of alternatives in the cell? This Account discusses the structure, affinity, and specificity of FHA domains and the formation of their functional structure. Although FHA domains share sequence identity at only five loop residues, they all fold into a beta-sandwich of two beta-sheets. The conserved arginine and serine of the recognition loops recognize the phosphorylation of the threonine targeted. Side chains emanating from loops that join beta-strand 4 with 5, 6 with 7, or 10 with 11 make specific contacts with amino acids of the ligand that tailor sequence preferences. Many FHA domains choose a partner in extended conformation, somewhat according to the residue three after the phosphothreonine in sequence (pT + 3 position). One group of FHA domains chooses a short carboxylate-containing side chain at pT + 3. Another group chooses a long, branched aliphatic side chain. A third group prefers other hydrophobic or uncharged polar side chains at pT + 3. However, another FHA domain instead chooses on the basis of pT - 2, pT - 3, and pT + 1 positions. An FHA domain from a marker of human cancer instead chooses a much longer protein fragment that adds a beta-strand to its beta-sheet and that presents hydrophobic residues from a novel helix to the usual recognition surface. This novel recognition site and more remote sites for the binding of other types of protein partners were predicted for the entire family

  3. The Mobius domain wall fermion algorithm

    DOE PAGES

    Brower, Richard C.; Neff, Harmut; Orginos, Kostas

    2017-07-22

    We present a review of the properties of generalized domain wall Fermions, based on a (real) Möbius transformation on the Wilson overlap kernel, discussing their algorithmic efficiency, the degree of explicit chiral violations measured by the residual mass (m res) and the Ward–Takahashi identities. The Möbius class interpolates between Shamir’s domain wall operator and Boriçi’s domain wall implementation of Neuberger’s overlap operator without increasing the number of Dirac applications per conjugate gradient iteration. A new scaling parameter (α) reduces chiral violations at finite fifth dimension (L s) but yields exactly the same overlap action in the limit L s →more » ∞ . Through the use of 4d Red/Black preconditioning and optimal tuning for the scaling α(L s), we show that chiral symmetry violations are typically reduced by an order of magnitude at fixed Ls . Here, we argue that the residual mass for a tuned Möbius algorithm with α = O(1/L s γ) for γ < 1 will eventually fall asymptotically as m res = O(1/L s 1+γ) in the case of a 5D Hamiltonian with out a spectral gap.« less

  4. The Mobius domain wall fermion algorithm

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

    Brower, Richard C.; Neff, Harmut; Orginos, Kostas

    We present a review of the properties of generalized domain wall Fermions, based on a (real) Möbius transformation on the Wilson overlap kernel, discussing their algorithmic efficiency, the degree of explicit chiral violations measured by the residual mass (m res) and the Ward–Takahashi identities. The Möbius class interpolates between Shamir’s domain wall operator and Boriçi’s domain wall implementation of Neuberger’s overlap operator without increasing the number of Dirac applications per conjugate gradient iteration. A new scaling parameter (α) reduces chiral violations at finite fifth dimension (L s) but yields exactly the same overlap action in the limit L s →more » ∞ . Through the use of 4d Red/Black preconditioning and optimal tuning for the scaling α(L s), we show that chiral symmetry violations are typically reduced by an order of magnitude at fixed Ls . Here, we argue that the residual mass for a tuned Möbius algorithm with α = O(1/L s γ) for γ < 1 will eventually fall asymptotically as m res = O(1/L s 1+γ) in the case of a 5D Hamiltonian with out a spectral gap.« less

  5. Separated matter and antimatter domains with vanishing domain walls

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

    Dolgov, A.D.; Godunov, S.I.; Rudenko, A.S.

    2015-10-01

    We present a model of spontaneous (or dynamical) C and CP violation where it is possible to generate domains of matter and antimatter separated by cosmologically large distances. Such C(CP) violation existed only in the early universe and later it disappeared with the only trace of generated baryonic and/or antibaryonic domains. So the problem of domain walls in this model does not exist. These features are achieved through a postulated form of interaction between inflaton and a new scalar field, realizing short time C(CP) violation.

  6. Minimization of Ohmic losses for domain wall motion in ferromagnetic nanowires

    NASA Astrophysics Data System (ADS)

    Abanov, Artem; Tretiakov, Oleg; Liu, Yang

    2011-03-01

    We study current-induced domain-wall motion in a narrow ferromagnetic wire. We propose a way to move domain walls with a resonant time-dependent current which dramatically decreases the Ohmic losses in the wire and allows driving of the domain wall with higher speed without burning the wire. For any domain wall velocity we find the time-dependence of the current needed to minimize the Ohmic losses. Below a critical domain-wall velocity specified by the parameters of the wire the minimal Ohmic losses are achieved by dc current. Furthermore, we identify the wire parameters for which the losses reduction from its dc value is the most dramatic. This work was supported by the NSF Grant No. 0757992 and Welch Foundation (A-1678).

  7. Complex oxide ferroelectrics: Electrostatic doping by domain walls

    DOE PAGES

    Maksymovych, Petro

    2015-06-19

    Electrically conducting interfaces can form, rather unexpectedly, by breaking the translational symmetry of electrically insulating complex oxides. For example, a nanometre-thick heteroepitaxial interface between electronically insulating LaAlO 3 and SrTiO 3 supports a 2D electron gas1 with high mobility of >1,000 cm 2 V -1 s -1 (ref. 2). Such interfaces can exhibit magnetism, superconductivity and phase transitions that may form the functional basis of future electronic devices2. A peculiar conducting interface can be created within a polar ferroelectric oxide by breaking the translational symmetry of the ferroelectric order parameter and creating a so-called ferroelectric domain wall (Fig. 1a,b). Ifmore » the direction of atomic displacements changes at the wall in such a way as to create a discontinuity in the polarization component normal to the wall (Fig. 1a), the domain wall becomes electrostatically charged. It may then attract compensating mobile charges of opposite sign produced by dopant ionization, photoexcitation or other effects, thereby locally, electrostatically doping the host ferroelectric film. In contrast to conductive interfaces between epitaxially grown oxides, domain walls can be reversibly created, positioned and shaped by electric fields, enabling reconfigurable circuitry within the same volume of the material. Now, writing in Nature Nanotechnology, Arnaud Crassous and colleagues at EPFL and University of Geneva demonstrate control and stability of charged conducting domain walls in ferroelectric thin films of BiFeO 3 down to the nanoscale.« less

  8. Nanoscale Origins of Ferroelastic Domain Wall Mobility in Ferroelectric Multilayers

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

    Huang, Hsin-Hui; Hong, Zijian; Xin, Huolin L.

    Here we investigate the nanoscale origins of ferroelastic domain wall motion in ferroelectric multilayer thin films that lead to giant electromechanical responses. We present direct evidence for complex underpinning factors that result in ferroelastic domain wall mobility using a combination of atomic-level aberration corrected scanning transmission electron microscopy and phase-field simulations in model epitaxial (001) tetragonal (T) PbZr xTi 1-xO 3 (PZT)/rhombohedral (R) PbZr xTi 1-xO 3 (PZT) bilayer heterostructures. The local electric dipole distribution is imaged on an atomic scale for a ferroelastic domain wall that nucleates in the R-layer and cuts through the composition breaking the T/R interface.more » Our studies reveal a highly complex polarization rotation domain structure that is nearly on the knife-edge at the vicinity of this wall. Induced phases, namely tetragonal-like and rhombohedral-like monoclinic were observed close to the interface, and exotic domain arrangements, such as a half-four-fold closure structure, are observed. Phase field simulations show this is due to the minimization of the excessive elastic and electrostatic energies driven by the enormous strain gradient present at the location of the ferroelastic domain walls. Thus, in response to an applied stimulus, such as an electric field, any polarization reorientation must minimize the elastic and electrostatic discontinuities due to this strain gradient, which would induce a dramatic rearrangement of the domain structure. This insight into the origins of ferroelastic domain wall motion will allow researchers to better “craft” such multilayered ferroelectric systems with precisely tailored domain wall functionality and enhanced sensitivity, which can be exploited for the next generation of integrated piezoelectric technologies.« less

  9. Nanoscale Origins of Ferroelastic Domain Wall Mobility in Ferroelectric Multilayers

    DOE PAGES

    Huang, Hsin-Hui; Hong, Zijian; Xin, Huolin L.; ...

    2016-10-31

    Here we investigate the nanoscale origins of ferroelastic domain wall motion in ferroelectric multilayer thin films that lead to giant electromechanical responses. We present direct evidence for complex underpinning factors that result in ferroelastic domain wall mobility using a combination of atomic-level aberration corrected scanning transmission electron microscopy and phase-field simulations in model epitaxial (001) tetragonal (T) PbZr xTi 1-xO 3 (PZT)/rhombohedral (R) PbZr xTi 1-xO 3 (PZT) bilayer heterostructures. The local electric dipole distribution is imaged on an atomic scale for a ferroelastic domain wall that nucleates in the R-layer and cuts through the composition breaking the T/R interface.more » Our studies reveal a highly complex polarization rotation domain structure that is nearly on the knife-edge at the vicinity of this wall. Induced phases, namely tetragonal-like and rhombohedral-like monoclinic were observed close to the interface, and exotic domain arrangements, such as a half-four-fold closure structure, are observed. Phase field simulations show this is due to the minimization of the excessive elastic and electrostatic energies driven by the enormous strain gradient present at the location of the ferroelastic domain walls. Thus, in response to an applied stimulus, such as an electric field, any polarization reorientation must minimize the elastic and electrostatic discontinuities due to this strain gradient, which would induce a dramatic rearrangement of the domain structure. This insight into the origins of ferroelastic domain wall motion will allow researchers to better “craft” such multilayered ferroelectric systems with precisely tailored domain wall functionality and enhanced sensitivity, which can be exploited for the next generation of integrated piezoelectric technologies.« less

  10. Structural and Histone Binding Ability Characterizations of Human PWWP Domains

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

    Wu, Hong; Zeng, Hong; Lam, Robert

    2013-09-25

    The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members,more » implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical {beta}-barrel core, an insertion motif between the second and third {beta}-strands and a C-terminal {alpha}-helix bundle. Both the canonical {beta}-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.« less

  11. Displacement Current in Domain Walls of Bismuth Ferrite

    NASA Astrophysics Data System (ADS)

    Prosandeev, Sergey; Yang, Yurong; Paillard, Charles; Bellaiche, L.

    2018-03-01

    In 1861, Maxwell conceived the idea of the displacement current, which then made laws of electrodynamics more complete and also resulted in the realization of devices exploiting such displacement current. Interestingly, it is presently unknown if such displacement current can result in large intrinsic ac current in ferroic systems possessing domains, despite the flurry of recent activities that have been devoted to domains and their corresponding conductivity in these compounds. Here, we report first-principles-based atomistic simulations that predict that the transverse (polarization-related) displacement currents of 71° and 109° domains in the prototypical BiFeO3 multiferroic material are significant at the walls of such domains and in the GHz regime, and, in fact, result in currents that are at least of the same order of magnitude than previously reported dc currents (that are likely extrinsic in nature and due to electrons). Such large, localized and intrinsic ac currents are found to originate from low-frequency vibrations at the domain walls, and may open the door to the design of novel devices functioning in the GHz or THz range and in which currents would be confined within the domain wall.

  12. Domain-wall trapping in a ferromagnetic nanowire network

    NASA Astrophysics Data System (ADS)

    Saitoh, E.; Tanaka, M.; Miyajima, H.; Yamaoka, T.

    2003-05-01

    The magnetic domain configuration in a submicron Ni81Fe19 wire network has been investigated by magnetic force microscopy. To improve the responsivity of the magnetic force microscope, an active quality factor autocontrol method was adopted. In the remanent state, domain walls were observed trapped firmly at the vertexes of the network. The magnetic domain configurations appear to minimize the exchange energy at the vertexes. These results indicate that the magnetic property of the ferromagnetic network can be described in terms of the uniform magnetic moments of the wires and interwire magnetic interactions at the vertexes. The observed structure of the domain walls is well reproduced by micromagnetic simulations.

  13. Microwave background distortions from domain walls

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Noetzold, Dirk

    1990-01-01

    Domain walls arising in a cosmic phase transition after decoupling were recently proposed as seeds for the formation of large scale structure. The distortion induced in the microwave background radiation is calculated in dependence of the wall thickness, surface density, scalar field potential, cosmic redshift and the velocity of the wall. It was found that the maximal redshift distortion for both spherical and planar walls is of the order pi G sigma H(sup -1)(sub 0), where sigma is the surface energy density and H(sup -1)(sub 0) the Hubble parameter. It was also found that, for a wall thickness smaller than the horizon, walls can be treated as infinitely thin, i.e., the redshift distortion is independent of the wall thickness and the specific form of the scalar potential. For planar walls moving with a Lorentz-factor gamma the redshift distortion is enhanced by gamma cubed.

  14. Domain wall assisted GMR head with spin-Hall effect

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

    Arun, R., E-mail: arunbdu@gmail.com; Sabareesan, P., E-mail: sendtosabari@gmail.com; Daniel, M., E-mail: danielcnld@gmail.com

    2016-05-06

    We theoretically study the dynamics of a field induced domain wall in the Py/Pt bi-layer structure in the presence of spin-Hall effect (SHE) by solving the Landau-Lifshitz-Gilbert (LLG) equation along with the adiabatic, nonadiabatic and SHE spin-transfer torques (STTs). It is observed that a weak magnetic field moves the domain wall with high velocity in the presence of SHE and the direction of the velocity is changed by changing the direction of the weak field. The numerical results show that the magnetization of the ferromagnetic layer can be reversed quickly through domain wall motion by changing the direction of amore » weak external field in the presence of SHE while the direction of current is fixed. The SHE reduces the magnetization reversal time of 1000 nm length strip by 14.7 ns. This study is extended to model a domain wall based GMR (Giant Magnetoresistance) read head with SHE.« less

  15. Magnetoelectric domain wall dynamics and its implications for magnetoelectric memory

    DOE PAGES

    Belashchenko, K. D.; Tchernyshyov, O.; Kovalev, Alexey A.; ...

    2016-03-30

    Domain wall dynamics in a magnetoelectric antiferromagnet is analyzed, and its implications for magnetoelectric memory applications are discussed. Cr 2O 3 is used in the estimates of the materials parameters. It is found that the domain wall mobility has a maximum as a function of the electric field due to the gyrotropic coupling induced by it. In Cr 2O 3, the maximal mobility of 0.1 m/(s Oe) is reached at E≈0.06 V/nm. Fields of this order may be too weak to overcome the intrinsic depinning field, which is estimated for B-doped Cr 2O 3. These major drawbacks for device implementationmore » can be overcome by applying a small in-plane shear strain, which blocks the domain wall precession. Domain wall mobility of about 0.7 m/(s Oe) can then be achieved at E = 0.2 V/nm. Furthermore, a split-gate scheme is proposed for the domain-wall controlled bit element; its extension to multiple-gate linear arrays can offer advantages in memory density, programmability, and logic functionality.« less

  16. Mapping small molecule binding data to structural domains

    PubMed Central

    2012-01-01

    Background Large-scale bioactivity/SAR Open Data has recently become available, and this has allowed new analyses and approaches to be developed to help address the productivity and translational gaps of current drug discovery. One of the current limitations of these data is the relative sparsity of reported interactions per protein target, and complexities in establishing clear relationships between bioactivity and targets using bioinformatics tools. We detail in this paper the indexing of targets by the structural domains that bind (or are likely to bind) the ligand within a full-length protein. Specifically, we present a simple heuristic to map small molecule binding to Pfam domains. This profiling can be applied to all proteins within a genome to give some indications of the potential pharmacological modulation and regulation of all proteins. Results In this implementation of our heuristic, ligand binding to protein targets from the ChEMBL database was mapped to structural domains as defined by profiles contained within the Pfam-A database. Our mapping suggests that the majority of assay targets within the current version of the ChEMBL database bind ligands through a small number of highly prevalent domains, and conversely the majority of Pfam domains sampled by our data play no currently established role in ligand binding. Validation studies, carried out firstly against Uniprot entries with expert binding-site annotation and secondly against entries in the wwPDB repository of crystallographic protein structures, demonstrate that our simple heuristic maps ligand binding to the correct domain in about 90 percent of all assessed cases. Using the mappings obtained with our heuristic, we have assembled ligand sets associated with each Pfam domain. Conclusions Small molecule binding has been mapped to Pfam-A domains of protein targets in the ChEMBL bioactivity database. The result of this mapping is an enriched annotation of small molecule bioactivity data and a

  17. Domain wall in a quantum anomalous Hall insulator as a magnetoelectric piston

    NASA Astrophysics Data System (ADS)

    Upadhyaya, Pramey; Tserkovnyak, Yaroslav

    2016-07-01

    We theoretically study the magnetoelectric coupling in a quantum anomalous Hall insulator state induced by interfacing a dynamic magnetization texture to a topological insulator. In particular, we propose that the quantum anomalous Hall insulator with a magnetic configuration of a domain wall, when contacted by electrical reservoirs, acts as a magnetoelectric piston. A moving domain wall pumps charge current between electrical leads in a closed circuit, while applying an electrical bias induces reciprocal domain-wall motion. This pistonlike action is enabled by a finite reflection of charge carriers via chiral modes imprinted by the domain wall. Moreover, we find that, when compared with the recently discovered spin-orbit torque-induced domain-wall motion in heavy metals, the reflection coefficient plays the role of an effective spin-Hall angle governing the efficiency of the proposed electrical control of domain walls. Quantitatively, this effective spin-Hall angle is found to approach a universal value of 2, providing an efficient scheme to reconfigure the domain-wall chiral interconnects for possible memory and logic applications.

  18. Molecular Evolution of the Oxygen-Binding Hemerythrin Domain

    PubMed Central

    Alvarez-Carreño, Claudia; Becerra, Arturo; Lazcano, Antonio

    2016-01-01

    Background The evolution of oxygenic photosynthesis during Precambrian times entailed the diversification of strategies minimizing reactive oxygen species-associated damage. Four families of oxygen-carrier proteins (hemoglobin, hemerythrin and the two non-homologous families of arthropodan and molluscan hemocyanins) are known to have evolved independently the capacity to bind oxygen reversibly, providing cells with strategies to cope with the evolutionary pressure of oxygen accumulation. Oxygen-binding hemerythrin was first studied in marine invertebrates but further research has made it clear that it is present in the three domains of life, strongly suggesting that its origin predated the emergence of eukaryotes. Results Oxygen-binding hemerythrins are a monophyletic sub-group of the hemerythrin/HHE (histidine, histidine, glutamic acid) cation-binding domain. Oxygen-binding hemerythrin homologs were unambiguously identified in 367/2236 bacterial, 21/150 archaeal and 4/135 eukaryotic genomes. Overall, oxygen-binding hemerythrin homologues were found in the same proportion as single-domain and as long protein sequences. The associated functions of protein domains in long hemerythrin sequences can be classified in three major groups: signal transduction, phosphorelay response regulation, and protein binding. This suggests that in many organisms the reversible oxygen-binding capacity was incorporated in signaling pathways. A maximum-likelihood tree of oxygen-binding hemerythrin homologues revealed a complex evolutionary history in which lateral gene transfer, duplications and gene losses appear to have played an important role. Conclusions Hemerythrin is an ancient protein domain with a complex evolutionary history. The distinctive iron-binding coordination site of oxygen-binding hemerythrins evolved first in prokaryotes, very likely prior to the divergence of Firmicutes and Proteobacteria, and spread into many bacterial, archaeal and eukaryotic species. The later

  19. Minimization of Ohmic Losses for Domain Wall Motion in a Ferromagnetic Nanowire

    NASA Astrophysics Data System (ADS)

    Tretiakov, O. A.; Liu, Y.; Abanov, Ar.

    2010-11-01

    We study current-induced domain-wall motion in a narrow ferromagnetic wire. We propose a way to move domain walls with a resonant time-dependent current which dramatically decreases the Ohmic losses in the wire and allows driving of the domain wall with higher speed without burning the wire. For any domain-wall velocity we find the time dependence of the current needed to minimize the Ohmic losses. Below a critical domain-wall velocity specified by the parameters of the wire the minimal Ohmic losses are achieved by dc current. Furthermore, we identify the wire parameters for which the losses reduction from its dc value is the most dramatic.

  20. Electrically controlled pinning of Dzyaloshinskii-Moriya domain walls

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

    Sato, Koji; Tretiakov, Oleg A., E-mail: olegt@imr.tohoku.ac.jp; School of Natural Sciences, Far Eastern Federal University, Vladivostok 690950

    We propose a method to all-electrically control a domain-wall position in a ferromagnetic nanowire with Dzyaloshinskii-Moriya interaction. The strength of this interaction can be controlled by an external electric field, which in turn allows a fine tuning of the pinning potential of a spin-spiral domain wall. It allows to create more mobile pinning sites and can also be advantageous for ultra-low power electronics.

  1. Domain walls of linear polarization in isotropic Kerr media

    NASA Astrophysics Data System (ADS)

    Louis, Y.; Sheppard, A. P.; Haelterman, M.

    1997-09-01

    We present a new type of domain-wall vector solitary waves in isotropic self-defocusing Kerr media. These domain walls consist of localized structures separating uniform field domains of orthogonal linear polarizations. They result from the interplay between diffraction, self-phase modulation and cross-phase modulation in cases where the nonlinear birefringence coefficient B = {χxyyx(3)}/{χxxxx(3)} is negative. Numerical simulations show that these new vector solitary waves are stable.

  2. Tunable short-wavelength spin wave excitation from pinned magnetic domain walls

    PubMed Central

    Van de Wiele, Ben; Hämäläinen, Sampo J.; Baláž, Pavel; Montoncello, Federico; van Dijken, Sebastiaan

    2016-01-01

    Miniaturization of magnonic devices for wave-like computing requires emission of short-wavelength spin waves, a key feature that cannot be achieved with microwave antennas. In this paper, we propose a tunable source of short-wavelength spin waves based on highly localized and strongly pinned magnetic domain walls in ferroelectric-ferromagnetic bilayers. When driven into oscillation by a microwave spin-polarized current, the magnetic domain walls emit spin waves with the same frequency as the excitation current. The amplitude of the emitted spin waves and the range of attainable excitation frequencies depend on the availability of domain wall resonance modes. In this respect, pinned domain walls in magnetic nanowires are particularly attractive. In this geometry, spin wave confinement perpendicular to the nanowire axis produces a multitude of domain wall resonances enabling efficient spin wave emission at frequencies up to 100 GHz and wavelengths down to 20 nm. At high frequency, the emission of spin waves in magnetic nanowires becomes monochromatic. Moreover, pinning of magnetic domain wall oscillators onto the same ferroelectric domain boundary in parallel nanowires guarantees good coherency between spin wave sources, which opens perspectives towards the realization of Mach-Zehnder type logic devices and sensors. PMID:26883893

  3. Domain wall kinetics of lithium niobate single crystals near the hexagonal corner

    NASA Astrophysics Data System (ADS)

    Choi, Ju Won; Ko, Do-Kyeong; Yu, Nan Ei; Kitamura, Kenji; Ro, Jung Hoon

    2015-03-01

    A mesospheric approach based on a simple microscopic 2D Ising model in a hexagonal lattice plane is proposed to explain macroscopic "asymmetric in-out domain wall motion" observation in the (0001) plane of MgO-doped stoichiometric lithium niobate. Under application of an electric field that was higher than the conventional coercive field (Ec) to the ferroelectric crystal, a natural hexagonal domain was obtained with walls that were parallel to the Y-axis of the crystal. When a fraction of the coercive field of around 0.1Ec is applied in the reverse direction, this hexagonal domain is shrunk (moved inward) from the corner site into a shape with a corner angle of around 150° and 15° wall slopes to the Y-axis. A flipped electric field of 0.15Ec is then applied to recover the natural hexagonal shape, and the 150° corner shape changes into a flat wall with 30° slope (moved outward). The differences in corner domain shapes between inward and outward domain motion were analyzed theoretically in terms of corner and wall site energies, which are described using the domain corner angle and wall slope with respect to the crystal Y-axis, respectively. In the inward domain wall motion case, the energy levels of the evolving 150° domain corner and 15° slope walls are most competitive, and could co-exist. In the outward case, the energy levels of corners with angles >180° are highly stable when compared with the possible domain walls; only a flat wall with 30° slope to the Y-axis is possible during outward motion.

  4. Use of bacteriophage cell wall-binding proteins for rapid diagnostics of Listeria.

    PubMed

    Schmelcher, Mathias; Loessner, Martin J

    2014-01-01

    Diagnostic protocols for food-borne bacterial pathogens such as Listeria need to be sensitive, specific, rapid, and inexpensive. Conventional culture methods are hampered by lengthy enrichment and incubation steps. Bacteriophage-derived high-affinity binding molecules (cell wall-binding domains, CBDs) specific for Listeria cells have recently been introduced as tools for detection and differentiation of this pathogen in foods. When coupled with magnetic separation, these proteins offer advantages in sensitivity and speed compared to the standard diagnostic methods. Furthermore, fusion of CBDs to differently colored fluorescent reporter proteins enables differentiation of Listeria strains in mixed cultures. This chapter provides protocols for detection of Listeria in food by CBD-based magnetic separation and subsequent multiplexed identification of strains of different serotypes with reporter-CBD fusion proteins.

  5. The Möbius domain wall fermion algorithm

    NASA Astrophysics Data System (ADS)

    Brower, Richard C.; Neff, Harmut; Orginos, Kostas

    2017-11-01

    We present a review of the properties of generalized domain wall Fermions, based on a (real) Möbius transformation on the Wilson overlap kernel, discussing their algorithmic efficiency, the degree of explicit chiral violations measured by the residual mass (mres) and the Ward-Takahashi identities. The Möbius class interpolates between Shamir's domain wall operator and Boriçi's domain wall implementation of Neuberger's overlap operator without increasing the number of Dirac applications per conjugate gradient iteration. A new scaling parameter (α) reduces chiral violations at finite fifth dimension (Ls) but yields exactly the same overlap action in the limit Ls → ∞. Through the use of 4d Red/Black preconditioning and optimal tuning for the scaling α(Ls) , we show that chiral symmetry violations are typically reduced by an order of magnitude at fixed Ls. We argue that the residual mass for a tuned Möbius algorithm with α = O(1 /Lsγ) for γ < 1 will eventually fall asymptotically as mres = O(1 /Ls1+γ) in the case of a 5D Hamiltonian with out a spectral gap.

  6. Stress-based control of magnetic nanowire domain walls in artificial multiferroic systems

    NASA Astrophysics Data System (ADS)

    Dean, J.; Bryan, M. T.; Schrefl, T.; Allwood, D. A.

    2011-01-01

    Artificial multiferroic systems, which combine piezoelectric and piezomagnetic materials, offer novel methods of controlling material properties. Here, we use combined structural and magnetic finite element models to show how localized strains in a piezoelectric film coupled to a piezomagnetic nanowire can attract and pin magnetic domain walls. Synchronous switching of addressable contacts enables the controlled movement of pinning sites, and hence domain walls, in the nanowire without applied magnetic field or spin-polarized current, irrespective of domain wall structure. Conversely, domain wall-induced strain in the piezomagnetic material induces a local potential difference in the piezoelectric, providing a mechanism for sensing domain walls. This approach overcomes the problems in magnetic nanowire memories of domain wall structure-dependent behavior and high power consumption. Nonvolatile random access or shift register memories based on these effects can achieve storage densities >1 Gbit/In2, sub-10 ns switching times, and power consumption <100 keV per operation.

  7. Phase Domain Walls in Weakly Nonlinear Deep Water Surface Gravity Waves.

    PubMed

    Tsitoura, F; Gietz, U; Chabchoub, A; Hoffmann, N

    2018-06-01

    We report a theoretical derivation, an experimental observation and a numerical validation of nonlinear phase domain walls in weakly nonlinear deep water surface gravity waves. The domain walls presented are connecting homogeneous zones of weakly nonlinear plane Stokes waves of identical amplitude and wave vector but differences in phase. By exploiting symmetry transformations within the framework of the nonlinear Schrödinger equation we demonstrate the existence of exact analytical solutions representing such domain walls in the weakly nonlinear limit. The walls are in general oblique to the direction of the wave vector and stationary in moving reference frames. Experimental and numerical studies confirm and visualize the findings. Our present results demonstrate that nonlinear domain walls do exist in the weakly nonlinear regime of general systems exhibiting dispersive waves.

  8. Phase Domain Walls in Weakly Nonlinear Deep Water Surface Gravity Waves

    NASA Astrophysics Data System (ADS)

    Tsitoura, F.; Gietz, U.; Chabchoub, A.; Hoffmann, N.

    2018-06-01

    We report a theoretical derivation, an experimental observation and a numerical validation of nonlinear phase domain walls in weakly nonlinear deep water surface gravity waves. The domain walls presented are connecting homogeneous zones of weakly nonlinear plane Stokes waves of identical amplitude and wave vector but differences in phase. By exploiting symmetry transformations within the framework of the nonlinear Schrödinger equation we demonstrate the existence of exact analytical solutions representing such domain walls in the weakly nonlinear limit. The walls are in general oblique to the direction of the wave vector and stationary in moving reference frames. Experimental and numerical studies confirm and visualize the findings. Our present results demonstrate that nonlinear domain walls do exist in the weakly nonlinear regime of general systems exhibiting dispersive waves.

  9. Antiferromagnetic domain wall as spin wave polarizer

    NASA Astrophysics Data System (ADS)

    Lan, Jin; Yu, Weichao; Xiao, Jiang

    Spin waves are collective excitations of local magnetizations that can effectively propagate information even in magnetic insulators. In antiferromagnet, spin waves are endowed with additional polarization freedom. Here we propose that the antiferromagnetic domain wall can act as a spin wave polarizer, which perfectly passes one linearly polarized spin wave while substantially reflects the perpendicular one. We show that the polarizing effect lies in the suppression of one linear polarization inside domain wall, in close analogy to the wire-grid optical polarizer. Our finding opens up new possibilities in magnonic processing by harnessing spin wave polarization in antiferromagnet.

  10. Dynamical evolution of domain walls in an expanding universe

    NASA Technical Reports Server (NTRS)

    Press, William H.; Ryden, Barbara S.; Spergel, David N.

    1989-01-01

    Whenever the potential of a scalar field has two or more separated, degenerate minima, domain walls form as the universe cools. The evolution of the resulting network of domain walls is calculated for the case of two potential minima in two and three dimensions, including wall annihilation, crossing, and reconnection effects. The nature of the evolution is found to be largely independent of the rate at which the universe expands. Wall annihilation and reconnection occur almost as fast as causality allows, so that the horizon volume is 'swept clean' and contains, at any time, only about one, fairly smooth, wall. Quantitative statistics are given. The total area of wall per volume decreases as the first power of time. The relative slowness of the decrease and the smoothness of the wall on the horizon scale make it impossible for walls to both generate large-scale structure and be consistent with quadrupole microwave background anisotropy limits.

  11. Domain walls in supersymmetric QCD: The taming of the zoo

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

    Binosi, Daniele; ter Veldhuis, Tonnis

    We provide a unified picture of the domain wall spectrum in supersymmetric QCD with N{sub c} colors and N{sub f} flavors of quarks in the (anti) fundamental representation. Within the framework of the Veneziano-Yankielowicz-Taylor effective Lagrangian, we consider domain walls connecting chiral symmetry breaking vacua, and we take the quark masses to be degenerate. For N{sub f}/N{sub c}<1/2, there is one BPS saturated domain wall for any value of the quark mass m. For 1/2{<=}N{sub f}/N{sub c}<1 there are two critical masses m{sub *} and m{sub **} which depend on the number of colors and flavors only through the ratiomore » N{sub f}/N{sub c}. If mwalls; if m{sub *}wall; and if m>m{sub **}, there is no domain wall. We numerically determine m{sub *} and m{sub **} as a function of N{sub f}/N{sub c}, and we find that m{sub **} approaches a constant value in the limit that this ratio goes to 1.« less

  12. Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding

    PubMed Central

    Ozdilek, Bagdeser A.; Thompson, Valery F.; Ahmed, Nasiha S.; White, Connor I.

    2017-01-01

    Abstract RGG/RG domains are the second most common RNA binding domain in the human genome, yet their RNA-binding properties remain poorly understood. Here, we report a detailed analysis of the RNA binding characteristics of intrinsically disordered RGG/RG domains from Fused in Sarcoma (FUS), FMRP and hnRNPU. For FUS, previous studies defined RNA binding as mediated by its well-folded domains; however, we show that RGG/RG domains are the primary mediators of binding. RGG/RG domains coupled to adjacent folded domains can achieve affinities approaching that of full-length FUS. Analysis of RGG/RG domains from FUS, FMRP and hnRNPU against a spectrum of contrasting RNAs reveals that each display degenerate binding specificity, while still displaying different degrees of preference for RNA. PMID:28575444

  13. Comparison of Current and Field Driven Domain Wall Motion in Beaded Permalloy Nanowires

    NASA Astrophysics Data System (ADS)

    Lage, Enno; Dutta, Sumit; Ross, Caroline A.

    2015-03-01

    Domain wall based devices are promising candidates for non-volatile memory devices with no static power consumption. A common approach is the use of (field assisted) current driven domain wall motion in magnetic nanowires. In such systems local variations in linewidth act as obstacles for propagating domain walls. In this study we compare simulated field driven and current driven domain wall motion in permalloy nanowires with anti-notches. The simulations were obtained using the Object Oriented MicroMagnetics Framework (OOMMF). The wires with a constant thickness of 8 nm exhibit linewidths ranging from 40 nm to 300 nm. Circular shaped anti-notches extend the linewidth locally by 10% to 30% and raise information about the domain wall propagation in such beaded nanowires. The results are interpreted in terms of the observed propagation behavior and summarized in maps indicating ranges of different ability to overcome the pinning caused by anti-notches of different sizes. Furthermore, regimes of favored domain wall type (transverse walls or vortex walls) and complex propagation effects like walker breakdown behavior or dynamic change between domain wall structures are identified The authors thank the German Academic Exchange Service (DAAD) for funding.

  14. Current at domain walls, roughly speaking: nanoscales studies of disorder roughening and conduction

    NASA Astrophysics Data System (ADS)

    Paruch, Patrycja

    2013-03-01

    Domain walls in (multi)ferroic materials are the thin elastic interfaces separating regions with different orientations of magnetisation, electric polarisation, or spontaneous strain. Understanding their behaviour, and controlling domain size and stability, is key for their integration into applications, while fundamentally, domain walls provide an excellent model system in which the rich physics of disordered elastic interfaces can be accesses. In addition, domain walls can present novel properties, quite different from those of their parent materials, making them potentially useful as active components in future nano-devices. Here, we present our atomic force microscopy studies of ferroelectric domain walls in epitaxial Pb(Zr0.2Ti0.8)O3 and BiFeO3 thin films, in which we use piezorespose force microscopy to show unusual domain wall roughening behaviour, with very localised disorder regions in the sample leading to a complex, multi-affine scaling of the domain wall shape. We also show the effects of temperature, environmental conditions, and defects on switching dynamics and domain wall roughness. We combine these observations with parallel conductive-tip atomic force microscopy current measurements, which also show highly localised variations in conduction, and highlight the key role played by oxygen vacancies in the observed domain wall conduction.

  15. Large exchange-dominated domain wall velocities in antiferromagnetically coupled nanowires

    NASA Astrophysics Data System (ADS)

    Kuteifan, Majd; Lubarda, M. V.; Fu, S.; Chang, R.; Escobar, M. A.; Mangin, S.; Fullerton, E. E.; Lomakin, V.

    2016-04-01

    Magnetic nanowires supporting field- and current-driven domain wall motion are envisioned for methods of information storage and processing. A major obstacle for their practical use is the domain-wall velocity, which is traditionally limited for low fields and currents due to the Walker breakdown occurring when the driving component reaches a critical threshold value. We show through numerical and analytical modeling that the Walker breakdown limit can be extended or completely eliminated in antiferromagnetically coupled magnetic nanowires. These coupled nanowires allow for large domain-wall velocities driven by field and/or current as compared to conventional nanowires.

  16. Geometrical control of pure spin current induced domain wall depinning.

    PubMed

    Pfeiffer, A; Reeve, R M; Voto, M; Savero-Torres, W; Richter, N; Vila, L; Attané, J P; Lopez-Diaz, L; Kläui, Mathias

    2017-03-01

    We investigate the pure spin-current assisted depinning of magnetic domain walls in half ring based Py/Al lateral spin valve structures. Our optimized geometry incorporating a patterned notch in the detector electrode, directly below the Al spin conduit, provides a tailored pinning potential for a transverse domain wall and allows for a precise control over the magnetization configuration and as a result the domain wall pinning. Due to the patterned notch, we are able to study the depinning field as a function of the applied external field for certain applied current densities and observe a clear asymmetry for the two opposite field directions. Micromagnetic simulations show that this can be explained by the asymmetry of the pinning potential. By direct comparison of the calculated efficiencies for different external field and spin current directions, we are able to disentangle the different contributions from the spin transfer torque, Joule heating and the Oersted field. The observed high efficiency of the pure spin current induced spin transfer torque allows for a complete depinning of the domain wall at zero external field for a charge current density of [Formula: see text] A m -2 , which is attributed to the optimal control of the position of the domain wall.

  17. Domain wall fermion and CP symmetry breaking

    NASA Astrophysics Data System (ADS)

    Fujikawa, Kazuo; Suzuki, Hiroshi

    2003-02-01

    We examine the CP properties of chiral gauge theory defined by a formulation of the domain wall fermion, where the light field variables q and q¯ together with Pauli-Villars fields Q and Q¯ are utilized. It is shown that this domain wall representation in the infinite flavor limit N=∞ is valid only in the topologically trivial sector, and that the conflict among lattice chiral symmetry, strict locality and CP symmetry still persists for finite lattice spacing a. The CP transformation generally sends one representation of lattice chiral gauge theory into another representation of lattice chiral gauge theory, resulting in the inevitable change of propagators. A modified form of lattice CP transformation motivated by the domain wall fermion, which keeps the chiral action in terms of the Ginsparg-Wilson fermion invariant, is analyzed in detail; this provides an alternative way to understand the breaking of CP symmetry at least in the topologically trivial sector. We note that the conflict with CP symmetry could be regarded as a topological obstruction. We also discuss the issues related to the definition of Majorana fermions in connection with the supersymmetric Wess-Zumino model on the lattice.

  18. Motion of a Spherical Domain Wall and the Large-Scale Structure Formation

    NASA Astrophysics Data System (ADS)

    Yamamoto, K.; Tomita, K.

    1991-11-01

    The evolution of a wall-like structure in the universe is investigated by assuming a simplified model of a domain wall. The domain wall is approximated as a thin spherical shell with domain wall-like matter, which is assumed to interact with dust-like dark matter in an entirely inelastic manner, and its motion in an expanding universe is numerically studied in the general-relativistic treatment. We evaluate the lifetime of the wall, which is defined as the characteristic time for the wall to shrink due to its own tension. It is necessary that this time is not smaller than the cosmic age, in order that the walls avoid the collapse to the present time and play an important role in the structure formation of the universe. It is shown that, in spite of the above interaction, the strong restriction is imposed on the surface density of the domain walls and the allowed values are too small to have any influences on the background model.

  19. Equilibrium binding behavior of magnesium to wall teichoic acid.

    PubMed

    Thomas, Kieth J; Rice, Charles V

    2015-10-01

    Peptidoglycan and teichoic acids are the major cell wall components of Gram-positive bacteria that obtain and sequester metal ions required for biochemical processes. The delivery of metals to the cytoplasmic membrane is aided by anionic binding sites within the peptidoglycan and along the phosphodiester polymer of teichoic acid. The interaction with metals is a delicate balance between the need for attraction and ion diffusion to the membrane. Likewise, metal chelation from the extracellular fluid must initially have strong binding energetics that weaken within the cell wall to enable ion release. We employed atomic absorption and equilibrium dialysis to measure the metal binding capacity and metal binding affinity of wall teichoic acid and Mg2+. Data show that Mg2+ binds to WTA with a 1:2Mg2+ to phosphate ratio with a binding capacity of 1.27 μmol/mg. The affinity of Mg2+ to WTA was also found to be 41×10(3) M(-1) at low metal concentrations and 1.3×10(3) M(-1) at higher Mg2+ concentrations due to weakening electrostatic effects. These values are lower than the values describing Mg2+ interactions with peptidoglycan. However, the binding capacity of WTA is 4 times larger than peptidoglycan. External WTA initially binds metals with positive cooperativity, but metal binding switches to negative cooperativity, whereas interior WTA binds metals with only negative cooperativity. The relevance of this work is to describe changes in metal binding behavior depending on environment. When metals are sparse, chelation is strong to ensure survival yet the binding weakens when essential minerals are abundant. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Strain induced parametric pumping of a domain wall and its depinning from a notch

    NASA Astrophysics Data System (ADS)

    Nepal, Rabindra; Gungordu, Utkan; Kovalev, Alexey

    Using Thiele's method and detailed micromagnetic simulations, we study resonant oscillation of a domain wall in a notch of a ferromagnetic nanowire due to the modulation of magnetic anisotropy by external AC strain. Such resonant oscillation results from the parametric pumping of domain wall by AC strain at frequency about double the free domain wall oscillation frequency, which is mainly determined by the perpendicular anisotropy and notch geometry. This effect leads to a substantial reduction in depinning field or current required to depin a domain wall from the notch, and offers a mechanism for efficient domain wall motion in a notched nanowire. Our theoretical model accounts for the pinning potential due to a notch by explicitly calculating ferromagnetic energy as a function of notch geometry parameters. We also find similar resonant domain wall oscillations and reduction in the domain wall depinning field or current due to surface acoustic wave in soft ferromagnetic nanowire without uniaxial anisotropy that energetically favors an in-plane domain wall. DOE Early Career Award DE-SC0014189 and DMR- 1420645.

  1. Oscillatory behavior of the domain wall dynamics in a curved cylindrical magnetic nanowire

    NASA Astrophysics Data System (ADS)

    Moreno, R.; Carvalho-Santos, V. L.; Espejo, A. P.; Laroze, D.; Chubykalo-Fesenko, O.; Altbir, D.

    2017-11-01

    Understanding the domain wall dynamics is an important issue in modern magnetism. Here we present results of domain wall displacement in curved cylindrical nanowires at a constant magnetic field. We show that the average velocity of a transverse domain wall increases with curvature. Contrary to what is observed in stripes, in a curved wire the transverse domain wall oscillates along and rotates around the nanowire with the same frequency. These results open the possibility of new oscillation-based applications.

  2. Domain wall and isocurvature perturbation problems in a supersymmetric axion model

    NASA Astrophysics Data System (ADS)

    Kawasaki, Masahiro; Sonomoto, Eisuke

    2018-04-01

    The axion causes two serious cosmological problems, domain wall and isocurvature perturbation problems. Linde pointed out that the isocurvature perturbations are suppressed when the Peccei-Quinn (PQ) scalar field takes a large value ˜Mpl (Planck scale) during inflation. In this case, however, the PQ field with large amplitude starts to oscillate after inflation, and large fluctuations of the PQ field are produced through parametric resonance, which leads to the formation of domain walls. We consider a supersymmetric axion model and examine whether domain walls are formed by using lattice simulation. It is found that the domain wall problem does not appear in the SUSY axion model when the initial value of the PQ field is less than 1 03×v , where v is the PQ symmetry breaking scale.

  3. Characterizing protein domain associations by Small-molecule ligand binding

    PubMed Central

    Li, Qingliang; Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.

    2012-01-01

    Background Protein domains are evolutionarily conserved building blocks for protein structure and function, which are conventionally identified based on protein sequence or structure similarity. Small molecule binding domains are of great importance for the recognition of small molecules in biological systems and drug development. Many small molecules, including drugs, have been increasingly identified to bind to multiple targets, leading to promiscuous interactions with protein domains. Thus, a large scale characterization of the protein domains and their associations with respect to small-molecule binding is of particular interest to system biology research, drug target identification, as well as drug repurposing. Methods We compiled a collection of 13,822 physical interactions of small molecules and protein domains derived from the Protein Data Bank (PDB) structures. Based on the chemical similarity of these small molecules, we characterized pairwise associations of the protein domains and further investigated their global associations from a network point of view. Results We found that protein domains, despite lack of similarity in sequence and structure, were comprehensively associated through binding the same or similar small-molecule ligands. Moreover, we identified modules in the domain network that consisted of closely related protein domains by sharing similar biochemical mechanisms, being involved in relevant biological pathways, or being regulated by the same cognate cofactors. Conclusions A novel protein domain relationship was identified in the context of small-molecule binding, which is complementary to those identified by traditional sequence-based or structure-based approaches. The protein domain network constructed in the present study provides a novel perspective for chemogenomic study and network pharmacology, as well as target identification for drug repurposing. PMID:23745168

  4. Retinoid Binding Properties of Nucleotide Binding Domain 1 of the Stargardt Disease-associated ATP Binding Cassette (ABC) Transporter, ABCA4*

    PubMed Central

    Biswas-Fiss, Esther E.; Affet, Stephanie; Ha, Malissa; Biswas, Subhasis B.

    2012-01-01

    The retina-specific ATP binding cassette transporter, ABCA4 protein, is associated with a broad range of inherited macular degenerations, including Stargardt disease, autosomal recessive cone rod dystrophy, and fundus flavimaculatus. In order to understand its role in retinal transport in rod out segment discs, we have investigated the interactions of the soluble domains of ABCA4 with both 11-cis- and all-trans-retinal. Using fluorescence anisotropy-based binding analysis and recombinant polypeptides derived from the amino acid sequences of the four soluble domains of ABCA4, we demonstrated that the nucleotide binding domain 1 (NBD1) specifically bound 11-cis-retinal. Its affinity for all-trans-retinal was markedly reduced. Stargardt disease-associated mutations in this domain resulted in attenuation of 11-cis-retinal binding. Significant differences in 11-cis-retinal binding affinities were observed between NBD1 and other cytoplasmic and lumenal domains of ABCA4. The results suggest a possible role of ABCA4 and, in particular, the NBD1 domain in 11-cis-retinal binding. These results also correlate well with a recent report on the in vivo role of ABCA4 in 11-cis-retinal transport. PMID:23144455

  5. Hemoglobin binding and catalytic heme extraction by IsdB near iron transporter domains.

    PubMed

    Bowden, Catherine F M; Verstraete, Meghan M; Eltis, Lindsay D; Murphy, Michael E P

    2014-04-15

    The Isd (iron-regulated surface determinant) system is a multiprotein transporter that allows bacterium Staphylococcus aureus to take up iron from hemoglobin (Hb) during human infection. In this system, IsdB is a cell wall-anchored surface protein that contains two near iron transporter (NEAT) domains, one of which binds heme. IsdB rapidly extracts heme from Hb and transfers it to IsdA for relay into the bacterial cell. Using a series of recombinant IsdB constructs that included at least one NEAT domain, we demonstrated that both domains are required to bind Hb with high affinity (KD = 0.42 ± 0.05 μM) and to extract heme from Hb. Moreover, IsdB extracted heme only from oxidized metHb, although it also bound oxyHb and the Hb-CO complex. In a reconstituted model of the biological heme relay pathway, IsdB catalyzed the transfer of heme from metHb to IsdA with a Km for metHb of 0.75 ± 0.07 μN and a kcat of 0.22 ± 0.01 s(-1). The latter is consistent with the transfer of heme from metHb to IsdB being the rate-limiting step. With both NEAT domains and the linker region present in a single contiguous polypeptide, high-affinity Hb binding was achieved, rapid heme uptake was observed, and multiple turnovers of heme extraction from metHb and transfer to IsdA were conducted, representing all known Hb-heme uptake functions of the full-length IsdB protein.

  6. Expanding RNA binding specificity and affinity of engineered PUF domains.

    PubMed

    Zhao, Yang-Yang; Mao, Miao-Wei; Zhang, Wen-Jing; Wang, Jue; Li, Hai-Tao; Yang, Yi; Wang, Zefeng; Wu, Jia-Wei

    2018-05-18

    Specific manipulation of RNA is necessary for the research in biotechnology and medicine. The RNA-binding domains of Pumilio/fem-3 mRNA binding factors (PUF domains) are programmable RNA binding scaffolds used to engineer artificial proteins that specifically modulate RNAs. However, the native PUF domains generally recognize 8-nt RNAs, limiting their applications. Here, we modify the PUF domain of human Pumilio1 to engineer PUFs that recognize RNA targets of different length. The engineered PUFs bind to their RNA targets specifically and PUFs with more repeats have higher binding affinity than the canonical eight-repeat domains; however, the binding affinity reaches the peak at those with 9 and 10 repeats. Structural analysis on PUF with nine repeats reveals a higher degree of curvature, and the RNA binding unexpectedly and dramatically opens the curved structure. Investigation of the residues positioned in between two RNA bases demonstrates that tyrosine and arginine have favored stacking interactions. Further tests on the availability of the engineered PUFs in vitro and in splicing function assays indicate that our engineered PUFs bind RNA targets with high affinity in a programmable way.

  7. Expanding RNA binding specificity and affinity of engineered PUF domains

    PubMed Central

    Zhao, Yang-Yang; Zhang, Wen-Jing; Wang, Jue; Li, Hai-Tao; Yang, Yi; Wang, Zefeng; Wu, Jia-Wei

    2018-01-01

    Abstract Specific manipulation of RNA is necessary for the research in biotechnology and medicine. The RNA-binding domains of Pumilio/fem-3 mRNA binding factors (PUF domains) are programmable RNA binding scaffolds used to engineer artificial proteins that specifically modulate RNAs. However, the native PUF domains generally recognize 8-nt RNAs, limiting their applications. Here, we modify the PUF domain of human Pumilio1 to engineer PUFs that recognize RNA targets of different length. The engineered PUFs bind to their RNA targets specifically and PUFs with more repeats have higher binding affinity than the canonical eight-repeat domains; however, the binding affinity reaches the peak at those with 9 and 10 repeats. Structural analysis on PUF with nine repeats reveals a higher degree of curvature, and the RNA binding unexpectedly and dramatically opens the curved structure. Investigation of the residues positioned in between two RNA bases demonstrates that tyrosine and arginine have favored stacking interactions. Further tests on the availability of the engineered PUFs in vitro and in splicing function assays indicate that our engineered PUFs bind RNA targets with high affinity in a programmable way. PMID:29490074

  8. Src binds cortactin through an SH2 domain cystine-mediated linkage.

    PubMed

    Evans, Jason V; Ammer, Amanda G; Jett, John E; Bolcato, Chris A; Breaux, Jason C; Martin, Karen H; Culp, Mark V; Gannett, Peter M; Weed, Scott A

    2012-12-15

    Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions.

  9. Src binds cortactin through an SH2 domain cystine-mediated linkage

    PubMed Central

    Evans, Jason V.; Ammer, Amanda G.; Jett, John E.; Bolcato, Chris A.; Breaux, Jason C.; Martin, Karen H.; Culp, Mark V.; Gannett, Peter M.; Weed, Scott A.

    2012-01-01

    Summary Tyrosine-kinase-based signal transduction mediated by modular protein domains is critical for cellular function. The Src homology (SH)2 domain is an important conductor of intracellular signaling that binds to phosphorylated tyrosines on acceptor proteins, producing molecular complexes responsible for signal relay. Cortactin is a cytoskeletal protein and tyrosine kinase substrate that regulates actin-based motility through interactions with SH2-domain-containing proteins. The Src kinase SH2 domain mediates cortactin binding and tyrosine phosphorylation, but how Src interacts with cortactin is unknown. Here we demonstrate that Src binds cortactin through cystine bonding between Src C185 in the SH2 domain within the phosphotyrosine binding pocket and cortactin C112/246 in the cortactin repeats domain, independent of tyrosine phosphorylation. Interaction studies show that the presence of reducing agents ablates Src-cortactin binding, eliminates cortactin phosphorylation by Src, and prevents Src SH2 domain binding to cortactin. Tandem MS/MS sequencing demonstrates cystine bond formation between Src C185 and cortactin C112/246. Mutational studies indicate that an intact cystine binding interface is required for Src-mediated cortactin phosphorylation, cell migration, and pre-invadopodia formation. Our results identify a novel phosphotyrosine-independent binding mode between the Src SH2 domain and cortactin. Besides Src, one quarter of all SH2 domains contain cysteines at or near the analogous Src C185 position. This provides a potential alternative mechanism to tyrosine phosphorylation for cysteine-containing SH2 domains to bind cognate ligands that may be widespread in propagating signals regulating diverse cellular functions. PMID:23097045

  10. Dispersive elastic properties of Dzyaloshinskii domain walls

    NASA Astrophysics Data System (ADS)

    Pellegren, James; Lau, Derek; Sokalski, Vincent

    Recent studies on the asymmetric field-driven growth of magnetic bubble domains in perpendicular thin films exhibiting an interfacial Dzyaloshinskii-Moriya interaction (DMI) have provided a wealth of experimental evidence to validate models of creep phenomena, as key properties of the domain wall (DW) can be altered with the application of an external in-plane magnetic field. While asymmetric growth behavior has been attributed to the highly anisotropic DW energy, σ (θ) , which results from the combination of DMI and the in-plane field, many experimental results remain anomalous. In this work, we demonstrate that the anisotropy of DW energy alters the elastic response of the DW as characterized by the surface stiffness, σ (θ) = σ (θ) + σ (θ) , and evaluate the impact of this stiffness on the creep law. We find that at in-plane fields larger than and antiparallel to the effective field due to DMI, the DW stiffness decreases rapidly, suggesting that higher energy walls can actually become more mobile than their low energy counterparts. This result is consistent with experiments on CoNi multilayer films where velocity curves for domain walls with DMI fields parallel and antiparallel to the applied field cross over at high in-plane fields.

  11. Domain wall motion in ferroelectrics: Barkhausen noise

    NASA Astrophysics Data System (ADS)

    Shur, V.; Rumyantsev, E.; Kozhevnikov, V.; Nikolaeva, E.; Shishkin, E.

    2002-03-01

    The switching current noise has been recorded during polarization reversal in single-crystalline gadolinium molybdate (GMO) and lithium tantalate (LT). Analysis of Barkhausen noise (BN) data allows to classify the noise types by determination of the critical indexes and fractal dimensions. BN is manifested as the short pulses during the polarization reversal. We have analyzed the BN data recorded in GMO and LT with various types of controlled domain structure. The data treatment in terms of probability distribution of duration, area and energy of individual pulses reveals the critical behavior typical for the fractal records in time. We used the Fourier transform and Hurst's rescaled range analysis for obtaining the Hurst factor, fractal dimension and classifying the noise types. We investigated by computer simulation the mechanism of sideways motion of 180O domain wall by nucleation at the wall taking into account the nuclei-nuclei interaction. It was shown that the moving domain walls display the fractal shape and their motion is accompanied by Flicker noise, which is in accord with experimental data. The research was made possible in part by Programs "Basic Research in Russian Universities" and "Priority Research in High School. Electronics", by Grant No. 01-02-17443 of RFBR, by Award No.REC-005 of CRDF.

  12. Domain walls and the C P anomaly in softly broken supersymmetric QCD

    NASA Astrophysics Data System (ADS)

    Draper, Patrick

    2018-04-01

    In ordinary QCD with light, degenerate, fundamental flavors, C P symmetry is spontaneously broken at θ =π , and domain wall solutions connecting the vacua can be constructed in chiral perturbation theory. In some cases the breaking of C P saturates a 't Hooft anomaly, and anomaly inflow requires nontrivial massless excitations on the domain walls. Analogously, C P can be spontaneously broken in supersymmetric QCD (SQCD) with light flavors and small soft breaking parameters. We study C P breaking and domain walls in softly broken SQCD with Nfwalls. Vanishing of the C P anomaly is associated with the existence of multiple domain wall trajectories through field space, including walls which support no nontrivial massless excitations. In cases with an anomaly such walls are forbidden, and their absence in the relevant SQCD theories can be seen directly from the geometry of the low energy field space. In the case Nf=N -1 , multiple approximately Bogomol'nyi-Prasad-Sommerfield walls connect the vacua. Corrections to their tensions can be computed at leading order in the soft breaking parameters, producing a phase diagram for the stable wall trajectory. We also comment on domain walls in the similar case of QCD with an adjoint and fundamental flavors, and on the impact of adding an axion in this theory.

  13. Revised Model of Calcium and Magnesium Binding to the Bacterial Cell Wall

    PubMed Central

    Thomas, Kieth J.; Rice, Charles V.

    2014-01-01

    Metals bind to the bacterial cell wall yet the binding mechanisms and affinity constants are not fully understood. The cell wall of gram positive bacteria is characterized by a thick layer of peptidoglycan and anionic teichoic acids anchored in the cytoplasmic membrane (lipoteichoic acid) or covalently bound to the cell wall (wall teichoic acid). The polyphosphate groups of teichoic acid provide one-half of the metal binding sites for calcium and magnesium, contradicting previous reports that calcium binding is 100% dependent on teichoic acid. The remaining binding sites are formed with the carboxyl units of peptidoglycan. In this work we report equilibrium association constants and total metal binding capacities for the interaction of calcium and magnesium ions with the bacterial cell wall. Metal binding is much stronger and previously reported. Curvature of Scatchard plots from the binding data and the resulting two regions of binding affinity suggest the presence of negative cooperative binding, meaning that the binding affinity decreases as more ions become bound to the sample. For Ca2+, Region I has a KA = (1.0 ± 0.2) × 106 M−1 and Region II has a KA = (0.075 ± 0.058) × 106 M−1. For Mg2+, KA1 = (1.5 ± 0.1) × 106 and KA2 = (0.17 ± 0.10) × 106. A binding capacity (η) is reported for both regions. However, since binding is still occurring in Region II, the total binding capacity is denoted by η2, which are 0.70 ± 0.04 µmol/mg and 0.67 ± 0.03 µmol/mg for Ca2+ and Mg2+ respectively. These data contradict the current paradigm of there being a single metal affinity value that is constant over a range of concentrations. We also find that measurement of equilibrium binding constants is highly sample dependent, suggesting a role for diffusion of metals through heterogeneous cell wall fragments. As a result, we are able to reconcile many contradictory theories that describe binding affinity and the binding mode of divalent metal cations. PMID:25315444

  14. Magnetic domain wall creep and depinning: A scalar field model approach

    NASA Astrophysics Data System (ADS)

    Caballero, Nirvana B.; Ferrero, Ezequiel E.; Kolton, Alejandro B.; Curiale, Javier; Jeudy, Vincent; Bustingorry, Sebastian

    2018-06-01

    Magnetic domain wall motion is at the heart of new magnetoelectronic technologies and hence the need for a deeper understanding of domain wall dynamics in magnetic systems. In this context, numerical simulations using simple models can capture the main ingredients responsible for the complex observed domain wall behavior. We present a scalar field model for the magnetization dynamics of quasi-two-dimensional systems with a perpendicular easy axis of magnetization which allows a direct comparison with typical experimental protocols, used in polar magneto-optical Kerr effect microscopy experiments. We show that the thermally activated creep and depinning regimes of domain wall motion can be reached and the effect of different quenched disorder implementations can be assessed with the model. In particular, we show that the depinning field increases with the mean grain size of a Voronoi tessellation model for the disorder.

  15. Coupling between Current and Dynamic Magnetization : from Domain Walls to Spin Waves

    NASA Astrophysics Data System (ADS)

    Lucassen, M. E.

    2012-05-01

    So far, we have derived some general expressions for domain-wall motion and the spin motive force. We have seen that the β parameter plays a large role in both subjects. In all chapters of this thesis, there is an emphasis on the determination of this parameter. We also know how to incorporate thermal fluctuations for rigid domain walls, as shown above. In Chapter 2, we study a different kind of fluctuations: shot noise. This noise is caused by the fact that an electric current consists of electrons, and therefore has fluctuations. In the process, we also compute transmission and reflection coefficients for a rigid domain wall, and from them the linear momentum transfer. More work on fluctuations is done in Chapter 3. Here, we consider a (extrinsically pinned) rigid domain wall under the influence of thermal fluctuations that induces a current via spin motive force. We compute how the resulting noise in the current is related to the β parameter. In Chapter 4 we look into in more detail into the spin motive forces from field driven domain walls. Using micro magnetic simulations, we compute the spin motive force due to vortex domain walls explicitly. As mentioned before, this gives qualitatively different results than for a rigid domain wall. The final subject in Chapter 5 is the application of the general expression for spin motive forces to magnons. Although this might seem to be unrelated to domain-wall motion, this calculation allows us to relate the β parameter to macroscopic transport coefficients. This work was supported by Stichting voor Fundamenteel Onderzoek der Materie (FOM), the Netherlands Organization for Scientific Research (NWO), and by the European Research Council (ERC) under the Seventh Framework Program (FP7).

  16. Three-dimensional (3D) structure prediction and function analysis of the chitin-binding domain 3 protein HD73_3189 from Bacillus thuringiensis HD73.

    PubMed

    Zhan, Yiling; Guo, Shuyuan

    2015-01-01

    Bacillus thuringiensis (Bt) is capable of producing a chitin-binding protein believed to be functionally important to bacteria during the stationary phase of its growth cycle. In this paper, the chitin-binding domain 3 protein HD73_3189 from B. thuringiensis has been analyzed by computer technology. Primary and secondary structural analyses demonstrated that HD73_3189 is negatively charged and contains several α-helices, aperiodical coils and β-strands. Domain and motif analyses revealed that HD73_3189 contains a signal peptide, an N-terminal chitin binding 3 domains, two copies of a fibronectin-like domain 3 and a C-terminal carbohydrate binding domain classified as CBM_5_12. Moreover, analysis predicted the protein's associated localization site to be the cell wall. Ligand site prediction determined that amino acid residues GLU-312, TRP-334, ILE-341 and VAL-382 exposed on the surface of the target protein exhibit polar interactions with the substrate.

  17. Magnetic domain wall gratings for magnetization reversal tuning and confined dynamic mode localization.

    PubMed

    Trützschler, Julia; Sentosun, Kadir; Mozooni, Babak; Mattheis, Roland; McCord, Jeffrey

    2016-08-04

    High density magnetic domain wall gratings are imprinted in ferromagnetic-antiferromagnetic thin films by local ion irradiation by which alternating head-to-tail-to-head-to-tail and head-to-head-to-tail-to-tail spatially overlapping domain wall networks are formed. Unique magnetic domain processes result from the interaction of anchored domain walls. Non-linear magnetization response is introduced by the laterally distributed magnetic anisotropy phases. The locally varying magnetic charge distribution gives rise to localized and guided magnetization spin-wave modes directly constrained by the narrow domain wall cores. The exchange coupled multiphase material structure leads to unprecedented static and locally modified dynamic magnetic material properties.

  18. Magnetic domain wall gratings for magnetization reversal tuning and confined dynamic mode localization

    NASA Astrophysics Data System (ADS)

    Trützschler, Julia; Sentosun, Kadir; Mozooni, Babak; Mattheis, Roland; McCord, Jeffrey

    2016-08-01

    High density magnetic domain wall gratings are imprinted in ferromagnetic-antiferromagnetic thin films by local ion irradiation by which alternating head-to-tail-to-head-to-tail and head-to-head-to-tail-to-tail spatially overlapping domain wall networks are formed. Unique magnetic domain processes result from the interaction of anchored domain walls. Non-linear magnetization response is introduced by the laterally distributed magnetic anisotropy phases. The locally varying magnetic charge distribution gives rise to localized and guided magnetization spin-wave modes directly constrained by the narrow domain wall cores. The exchange coupled multiphase material structure leads to unprecedented static and locally modified dynamic magnetic material properties.

  19. Characteristic microwave background distortions from collapsing domain wall bubbles

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Noetzold, Dirk

    1990-01-01

    The magnitude and angular pattern of distortions of the microwave background are analyzed by collapsing spherical domain walls. A characteristic pattern of redshift distortions of red or blue spikes surrounded by blue discs was found. The width and height of a spike is related to the diameter and magnitude of the disc. A measurement of the relations between these quantities thus can serve as an unambiguous indicator for a collapsing spherical domain wall. From the redshift distortion in the blue discs an upper bound was found on the surface energy density of the walls sigma is less than or approximately 8 MeV cubed.

  20. Micromagnetic analysis of current-induced domain wall motion in a bilayer nanowire with synthetic antiferromagnetic coupling

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

    Komine, Takashi, E-mail: komine@mx.ibaraki.ac.jp; Aono, Tomosuke

    We demonstrate current-induced domain wall motion in bilayer nanowire with synthetic antiferromagnetic (SAF) coupling by modeling two body problems for motion equations of domain wall. The influence of interlayer exchange coupling and magnetostatic interactions on current-induced domain wall motion in SAF nanowires was also investigated. By assuming the rigid wall model for translational motion, the interlayer exchange coupling and the magnetostatic interaction between walls and domains in SAF nanowires enhances domain wall speed without any spin-orbit-torque. The enhancement of domain wall speed was discussed by energy distribution as a function of wall angle configuration in bilayer nanowires.

  1. A Thermophilic Phage Endolysin Fusion to a Clostridium perfringens-Specific Cell Wall Binding Domain Creates an Anti-Clostridium Antimicrobial with Improved Thermostability.

    PubMed

    Swift, Steven M; Seal, Bruce S; Garrish, Johnna K; Oakley, Brian B; Hiett, Kelli; Yeh, Hung-Yueh; Woolsey, Rebekah; Schegg, Kathleen M; Line, John Eric; Donovan, David M

    2015-06-12

    Clostridium perfringens is the third leading cause of human foodborne bacterial disease and is the presumptive etiologic agent of necrotic enteritis among chickens. Treatment of poultry with antibiotics is becoming less acceptable. Endolysin enzymes are potential replacements for antibiotics. Many enzymes are added to animal feed during production and are subjected to high-heat stress during feed processing. To produce a thermostabile endolysin for treating poultry, an E. coli codon-optimized gene was synthesized that fused the N-acetylmuramoyl-L-alanine amidase domain from the endolysin of the thermophilic bacteriophage ɸGVE2 to the cell-wall binding domain (CWB) from the endolysin of the C. perfringens-specific bacteriophage ɸCP26F. The resulting protein, PlyGVE2CpCWB, lysed C. perfringens in liquid and solid cultures. PlyGVE2CpCWB was most active at pH 8, had peak activity at 10 mM NaCl, 40% activity at 150 mM NaCl and was still 16% active at 600 mM NaCl. The protein was able to withstand temperatures up to 50° C and still lyse C. perfringens. Herein, we report the construction and characterization of a thermostable chimeric endolysin that could potentially be utilized as a feed additive to control the bacterium during poultry production.

  2. Intrinsic domain wall flexing from current-induced spin torque

    NASA Astrophysics Data System (ADS)

    Golovatski, Elizabeth; Flatté, Michael

    2012-02-01

    Spin torque generated by coherent carrier transport in domain walls [1] is a major component in the development of spintronic devices [2]. We model spin torque in N'eel walls [3] using a piecewise linear transfer-matrix method [4] to calculate spin torque on interior wall segments. For a π wall with a total positive torque (current left-to-right), we find the largest positive and negative spin torques left of the central region, 4-5 orders of magnitude larger than the center. The wall's rightward push comes from the back of the wall; all other significant regions pull to the left. Adding a second wall (both walls with positive total torque) changes the first wall little, but produces spin torques in the second wall with large canceling torques on the left, and the push rightward from a smaller torque on the right. The gradient of torque across the wall generates an intrinsic domain wall flexing (distinct from extrinsic wall flexing from pinning centers [5]). Work supported by an ARO MURI.[4pt] [1] M. Yamanouchi et al., Nature 428, 539 (2004).[0pt] [2] S. Parkin et al., Science 320, 190 (2008)[0pt] [3] G. Vignale and M. Flatt'e, Phys. Rev. Lett. 89, 098302 (2002)[0pt] [4] E. Golovatski and M. Flatt'e, Phys. Rev. B, 84, 115210 (2011)[0pt] [5] A. Balk et al., Phys. Rev. Lett. 107, 077205 (2011).

  3. Functional and structural characterization of a novel putative cysteine protease cell wall-modifying multi-domain enzyme selected from a microbial metagenome.

    PubMed

    Faheem, Muhammad; Martins-de-Sa, Diogo; Vidal, Julia F D; Álvares, Alice C M; Brandão-Neto, José; Bird, Louise E; Tully, Mark D; von Delft, Frank; Souto, Betulia M; Quirino, Betania F; Freitas, Sonia M; Barbosa, João Alexandre R G

    2016-12-09

    A current metagenomics focus is to interpret and transform collected genomic data into biological information. By combining structural, functional and genomic data we have assessed a novel bacterial protein selected from a carbohydrate-related activity screen in a microbial metagenomic library from Capra hircus (domestic goat) gut. This uncharacterized protein was predicted as a bacterial cell wall-modifying enzyme (CWME) and shown to contain four domains: an N-terminal, a cysteine protease, a peptidoglycan-binding and an SH3 bacterial domain. We successfully cloned, expressed and purified this putative cysteine protease (PCP), which presented autoproteolytic activity and inhibition by protease inhibitors. We observed cell wall hydrolytic activity and ampicillin binding capacity, a characteristic of most bacterial CWME. Fluorimetric binding analysis yielded a K b of 1.8 × 10 5  M -1 for ampicillin. Small-angle X-ray scattering (SAXS) showed a maximum particle dimension of 95 Å with a real-space R g of 28.35 Å. The elongated molecular envelope corroborates the dynamic light scattering (DLS) estimated size. Furthermore, homology modeling and SAXS allowed the construction of a model that explains the stability and secondary structural changes observed by circular dichroism (CD). In short, we report a novel cell wall-modifying autoproteolytic PCP with insight into its biochemical, biophysical and structural features.

  4. Microwave a.c. conductivity of domain walls in ferroelectric thin films

    DOE PAGES

    Tselev, Alexander; Yu, Pu; Cao, Ye; ...

    2016-05-31

    Ferroelectric domain walls are of great interest as elementary building blocks for future electronic devices due to their intrinsic few-nanometre width, multifunctional properties and field-controlled topology. To realize the electronic functions, domain walls are required to be electrically conducting and addressable non-destructively. However, these properties have been elusive because conducting walls have to be electrically charged, which makes them unstable and uncommon in ferroelectric materials. Here we reveal that spontaneous and recorded domain walls in thin films of lead zirconate and bismuth ferrite exhibit large conductance at microwave frequencies despite being insulating at d.c. We explain this effect by morphologicalmore » roughening of the walls and local charges induced by disorder with the overall charge neutrality. a.c. conduction is immune to large contact resistance enabling completely non-destructive walls read-out. Finally, this demonstrates a technological potential for harnessing a.c. conduction for oxide electronics and other materials with poor d.c. conduction, particularly at the nanoscale.« less

  5. Microwave a.c. conductivity of domain walls in ferroelectric thin films

    PubMed Central

    Tselev, Alexander; Yu, Pu; Cao, Ye; Dedon, Liv R.; Martin, Lane W.; Kalinin, Sergei V.; Maksymovych, Petro

    2016-01-01

    Ferroelectric domain walls are of great interest as elementary building blocks for future electronic devices due to their intrinsic few-nanometre width, multifunctional properties and field-controlled topology. To realize the electronic functions, domain walls are required to be electrically conducting and addressable non-destructively. However, these properties have been elusive because conducting walls have to be electrically charged, which makes them unstable and uncommon in ferroelectric materials. Here we reveal that spontaneous and recorded domain walls in thin films of lead zirconate and bismuth ferrite exhibit large conductance at microwave frequencies despite being insulating at d.c. We explain this effect by morphological roughening of the walls and local charges induced by disorder with the overall charge neutrality. a.c. conduction is immune to large contact resistance enabling completely non-destructive walls read-out. This demonstrates a technological potential for harnessing a.c. conduction for oxide electronics and other materials with poor d.c. conduction, particularly at the nanoscale. PMID:27240997

  6. Characteristic microwave-background distortions from collapsing spherical domain walls

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Notzold, Dirk

    1990-01-01

    The redshift distortion induced by collapsing spherical domain walls is calculated. The most frequent microwave background distortions are found to occur at large angles in the form of blue disks. This is the angular region currently measured by the COBE satellite. COBE could therefore detect signals predicted here for domain walls with surface energy density of the order of MeV. Such values for sigma are proposed in the late-time phase-transition scenario of Hill et al. (1989).

  7. Enhancement of Local Photovoltaic Current at Ferroelectric Domain Walls in BiFeO3.

    PubMed

    Yang, Ming-Min; Bhatnagar, Akash; Luo, Zheng-Dong; Alexe, Marin

    2017-02-20

    Domain walls, which are intrinsically two dimensional nano-objects exhibiting nontrivial electronic and magnetic behaviours, have been proven to play a crucial role in photovoltaic properties of ferroelectrics. Despite this recognition, the electronic properties of domain walls under illumination until now have been accessible only to macroscopic studies and their effects upon the conduction of photovoltaic current still remain elusive. The lack of understanding hinders the developing of nanoscale devices based on ferroelectric domain walls. Here, we directly characterize the local photovoltaic and photoconductive properties of 71° domain walls on BiFeO 3 thin films with a nanoscale resolution. Local photovoltaic current, proven to be driven by the bulk photovoltaic effect, has been probed over the whole illuminated surface by using a specially designed photoelectric atomic force microscopy and found to be significantly enhanced at domain walls. Additionally, spatially resolved photoconductive current distribution reveals a higher density of excited carriers at domain walls in comparison with domains. Our measurements demonstrate that domain wall enhanced photovoltaic current originates from its high conduction rather than the internal electric field. This photoconduction facilitated local photovoltaic current is likely to be a universal property of topological defects in ferroelectric semiconductors.

  8. Functional Properties at Domain Walls in BiFeO3: Electrical, Magnetic, and Structural investigations

    NASA Astrophysics Data System (ADS)

    He, Qing; Yang, C.-H.; Yu, P.; Gajek, M.; Seidel, J.; Ramesh, R.; Wang, F.; Chu, Y.-H.; Martin, L. W.; Spaldin, N.; Rother, A.

    2009-03-01

    BiFeO3 (BFO) is a widely studied robust ferroelectric, antiferromagnetic multiferroic. Conducting-atomic force microscopy studies reveal the presence of enhanced conductivity at certain types of domain walls in BFO. We have completed detailed TEM studies of the physical structure at these domain walls as well as in-depth DFT calculations of the evolution of electronic structure at these domain walls. These studies reveal two major contributions to the observed conduction: the formation of an electrostatic potential at the domain walls as well as a structurally-driven change in the electronic structure (i.e., a lower band gap locally) at the domain walls. We will discuss the use of optical characterization techniques as a way of probing this change in electronic structure at domain walls as well as detailed IV characterization both in atmospheric and UHV environments. Finally, the evolution of magnetism at these domain walls has been studied through the use of photoemission measurements. Initial findings point to a significant change in the magnetic order at these domain walls in BFO.

  9. Anomaly inflow on QCD axial domain-walls and vortices

    NASA Astrophysics Data System (ADS)

    Fukushima, Kenji; Imaki, Shota

    2018-06-01

    We study the chiral effective theory in the presence of quantum chromodynamics (QCD) vortices. Gauge invariance requires novel terms from vortex singularities in the gauged Wess-Zumino-Witten action, which incorporate anomaly-induced currents along the vortices. We examine these terms for systems with QCD axial domain-walls bounded by vortices (vortons) under magnetic fields. We discuss how the baryon and electric charge conservations are satisfied in these systems through interplay between domain-walls and vortices, manifesting Callan-Harvey's mechanism of anomaly inflow.

  10. OST-HTH: a novel predicted RNA-binding domain

    PubMed Central

    2010-01-01

    Background The mechanism by which the arthropod Oskar and vertebrate TDRD5/TDRD7 proteins nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. Using sequence profile searches we identify a novel domain in these proteins that is widely conserved across eukaryotes and bacteria. Results Using contextual information from domain architectures, sequence-structure superpositions and available functional information we predict that this domain is likely to adopt the winged helix-turn-helix fold and bind RNA with a potential specificity for dsRNA. We show that in eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. Conclusions Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized domain (DUF88). We present evidence that it is an RNAse belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains and might be recruited to degrade certain RNAs. Reviewers This article was reviewed by Sandor Pongor and Arcady Mushegian. PMID:20302647

  11. Domain-wall excitations in the two-dimensional Ising spin glass

    NASA Astrophysics Data System (ADS)

    Khoshbakht, Hamid; Weigel, Martin

    2018-02-01

    The Ising spin glass in two dimensions exhibits rich behavior with subtle differences in the scaling for different coupling distributions. We use recently developed mappings to graph-theoretic problems together with highly efficient implementations of combinatorial optimization algorithms to determine exact ground states for systems on square lattices with up to 10 000 ×10 000 spins. While these mappings only work for planar graphs, for example for systems with periodic boundary conditions in at most one direction, we suggest here an iterative windowing technique that allows one to determine ground states for fully periodic samples up to sizes similar to those for the open-periodic case. Based on these techniques, a large number of disorder samples are used together with a careful finite-size scaling analysis to determine the stiffness exponents and domain-wall fractal dimensions with unprecedented accuracy, our best estimates being θ =-0.2793 (3 ) and df=1.273 19 (9 ) for Gaussian couplings. For bimodal disorder, a new uniform sampling algorithm allows us to study the domain-wall fractal dimension, finding df=1.279 (2 ) . Additionally, we also investigate the distributions of ground-state energies, of domain-wall energies, and domain-wall lengths.

  12. Theory of Current-Driven Domain Wall Motion

    NASA Astrophysics Data System (ADS)

    Tatara, Gen

    2004-03-01

    Current-induced motion of a domain wall is studied starting from a microscopic Hamiltonian with an exchange interaction between conduction electrons and spins of the wall [1]. With a key observation that the position X and the angle φ0 the wall magnetization forms with the easy plane are the proper collective coordinates to describe its dynamics, it follows straightforwardly that the electric current affects the wall motion in two different ways, in agreement with Berger's pioneering observations[2]. The first is as a force, or momentum transfer, due to the reflection of conduction electrons. This force is proportional to the charge current j and wall resistivity ρ_w, and hence becomes important in thin walls. The other is as a spin torque or spin transfer[3], which is dominant for thick walls where the spin of conduction electron follows the magnetization adiabatically. The motion of a domain wall under a steady current is studied in two limiting cases. In the adiabatic case, we show that even without a pinning force, there is a threshold spin current, j_s^cr∝ K_⊥λ, below which the wall does not move (K_⊥ and λ being the hard-axis magnetic anisotropy and wall thickness, respectively). Below the threshold, the transferred angular momentum is used to shift φ0 and not to the wall motion. The pinning potential V0 affects j_s^cr only if it is very strong, V0 > K_⊥/α, where α is the damping parameter in the Landau-Lifshits-Gilbert equation. Therefore, the critical current for the adiabatic wall does not suffer very much from weak pinning, which is consistent with experimental observations[4]. The wall velocity after depinning is found to be ∝[(j_s/j_s^cr)^2-1]^1/2. In the case of thin wall, driven by a force ∝ ρw j, the critical current density is given by j^cr∝ V_0/ρ_w. In nanocontacts, this is estimated to be ˜ 10^7[A/m^2]. This small critical current would be advantageous for device application. [1] G.Tatara and H.Kohno, cond-mat/0308464

  13. Domain wall and isocurvature perturbation problems in axion models

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

    Kawasaki, Masahiro; Yoshino, Kazuyoshi; Yanagida, Tsutomu T., E-mail: kawasaki@icrr.u-tokyo.ac.jp, E-mail: tsutomu.tyanagida@ipmu.jp, E-mail: yoshino@icrr.u-tokyo.ac.jp

    2013-11-01

    Axion models have two serious cosmological problems, domain wall and isocurvature perturbation problems. In order to solve these problems we investigate the Linde's model in which the field value of the Peccei-Quinn (PQ) scalar is large during inflation. In this model the fluctuations of the PQ field grow after inflation through the parametric resonance and stable axionic strings may be produced, which results in the domain wall problem. We study formation of axionic strings using lattice simulations. It is found that in chaotic inflation the axion model is free from both the domain wall and the isocurvature perturbation problems ifmore » the initial misalignment angle θ{sub a} is smaller than O(10{sup −2}). Furthermore, axions can also account for the dark matter for the breaking scale v ≅ 10{sup 12−16} GeV and the Hubble parameter during inflation H{sub inf}∼<10{sup 11−12} GeV in general inflation models.« less

  14. FRW and domain walls in higher spin gravity

    NASA Astrophysics Data System (ADS)

    Aros, R.; Iazeolla, C.; Noreña, J.; Sezgin, E.; Sundell, P.; Yin, Y.

    2018-03-01

    We present exact solutions to Vasiliev's bosonic higher spin gravity equations in four dimensions with positive and negative cosmological constant that admit an interpretation in terms of domain walls, quasi-instantons and Friedman-Robertson-Walker (FRW) backgrounds. Their isometry algebras are infinite dimensional higher-spin extensions of spacetime isometries generated by six Killing vectors. The solutions presented are obtained by using a method of holomorphic factorization in noncommutative twistor space and gauge functions. In interpreting the solutions in terms of Fronsdal-type fields in space-time, a field-dependent higher spin transformation is required, which is implemented at leading order. To this order, the scalar field solves Klein-Gordon equation with conformal mass in ( A) dS 4 . We interpret the FRW solution with de Sitter asymptotics in the context of inflationary cosmology and we expect that the domain wall and FRW solutions are associated with spontaneously broken scaling symmetries in their holographic description. We observe that the factorization method provides a convenient framework for setting up a perturbation theory around the exact solutions, and we propose that the nonlinear completion of particle excitations over FRW and domain wall solutions requires black hole-like states.

  15. Eavesdropping on spin waves inside the domain-wall nanochannel via three-magnon processes

    NASA Astrophysics Data System (ADS)

    Zhang, Beining; Wang, Zhenyu; Cao, Yunshan; Yan, Peng; Wang, X. R.

    2018-03-01

    One recent breakthrough in the field of magnonics is the experimental realization of reconfigurable spin-wave nanochannels formed by a magnetic domain wall with a width of 10-100 nm [Wagner et al., Nat. Nano. 11, 432 (2016), 10.1038/nnano.2015.339]. This remarkable progress enables an energy-efficient spin-wave propagation with a well-defined wave vector along its propagating path inside the wall. In the mentioned experiment, a microfocus Brillouin light scattering spectroscopy was taken in a line-scans manner to measure the frequency of the bounded spin wave. Due to their localization nature, the confined spin waves can hardly be detected from outside the wall channel, which guarantees the information security to some extent. In this work, we theoretically propose a scheme to detect/eavesdrop on the spin waves inside the domain-wall nanochannel via nonlinear three-magnon processes. We send a spin wave (ωi,ki) in one magnetic domain to interact with the bounded mode (ωb,kb) in the wall, where kb is parallel with the domain-wall channel defined as the z ̂ axis. Two kinds of three-magnon processes, i.e., confluence and splitting, are expected to occur. The confluence process is conventional: conservation of energy and momentum parallel with the wall indicates a transmitted wave in the opposite domain with ω (k ) =ωi+ωb and (ki+kb-k ) .z ̂=0 , while the momentum perpendicular to the domain wall is not necessary to be conserved due to the nonuniform internal field near the wall. We predict a stimulated three-magnon splitting (or "magnon laser") effect: the presence of a bound magnon propagating along the domain wall channel assists the splitting of the incident wave into two modes, one is ω1=ωb,k1=kb identical to the bound mode in the channel, and the other one is ω2=ωi-ωb with (ki-kb-k2) .z ̂=0 propagating in the opposite magnetic domain. Micromagnetic simulations confirm our theoretical analysis. These results demonstrate that one is able to uniquely

  16. Enhancement of Local Photovoltaic Current at Ferroelectric Domain Walls in BiFeO3

    PubMed Central

    Yang, Ming-Min; Bhatnagar, Akash; Luo, Zheng-Dong; Alexe, Marin

    2017-01-01

    Domain walls, which are intrinsically two dimensional nano-objects exhibiting nontrivial electronic and magnetic behaviours, have been proven to play a crucial role in photovoltaic properties of ferroelectrics. Despite this recognition, the electronic properties of domain walls under illumination until now have been accessible only to macroscopic studies and their effects upon the conduction of photovoltaic current still remain elusive. The lack of understanding hinders the developing of nanoscale devices based on ferroelectric domain walls. Here, we directly characterize the local photovoltaic and photoconductive properties of 71° domain walls on BiFeO3 thin films with a nanoscale resolution. Local photovoltaic current, proven to be driven by the bulk photovoltaic effect, has been probed over the whole illuminated surface by using a specially designed photoelectric atomic force microscopy and found to be significantly enhanced at domain walls. Additionally, spatially resolved photoconductive current distribution reveals a higher density of excited carriers at domain walls in comparison with domains. Our measurements demonstrate that domain wall enhanced photovoltaic current originates from its high conduction rather than the internal electric field. This photoconduction facilitated local photovoltaic current is likely to be a universal property of topological defects in ferroelectric semiconductors. PMID:28216672

  17. Spontaneous Symmetry Breaking of Domain Walls in Phase-Competing Regions

    NASA Astrophysics Data System (ADS)

    Ishizuka, Hiroaki; Yamada, Yasusada; Nagaosa, Naoto

    2018-05-01

    In this study, we investigate the nature of domain walls in an ordered phase in the phase-competing region of two Ising-type order parameters. We consider a two-component ϕ4 theory and show that the domain wall of the ground-state (primary) order parameter shows a second-order phase transition associated with the secondary order parameter of the competing phase; the effective theory of the phase transition is given by the Landau theory of an Ising-type phase transition. We find that the phase boundary of this phase transition is different from the spinodal line of the competing order. The phase transition is detected experimentally by the divergence of the susceptibility corresponding to the secondary order when the temperature is quenched to introduce the domain walls.

  18. Current-induced three-dimensional domain wall propagation in cylindrical NiFe nanowires

    NASA Astrophysics Data System (ADS)

    Wong, D. W.; Purnama, I.; Lim, G. J.; Gan, W. L.; Murapaka, C.; Lew, W. S.

    2016-04-01

    We report on the magnetization configurations in single NiFe cylindrical nanowires grown by template-assisted electrodeposition. Angular anisotropic magnetoresistance measurements reveal that a three-dimensional helical domain wall is formed naturally upon relaxation from a saturated state. Micromagnetic simulations support the helical domain wall properties and its reversal process, which involves a splitting of the clockwise and anticlockwise vortices. When a pulsed current is applied to the nanowire, the helical domain wall propagation is observed with a minimum current density needed to overcome its intrinsic pinning.

  19. Magnetic field control of 90°, 180°, and 360° domain wall resistance

    NASA Astrophysics Data System (ADS)

    Majidi, Roya

    2012-10-01

    In the present work, we have compared the resistance of the 90°, 180°, and 360° domain walls in the presence of external magnetic field. The calculations are based on the Boltzmann transport equation within the relaxation time approximation. One-dimensional Néel-type domain walls between two domains whose magnetization differs by angle of 90°, 180°, and 360° are considered. The results indicate that the resistance of the 360° DW is more considerable than that of the 90° and 180° DWs. It is also found that the domain wall resistance can be controlled by applying transverse magnetic field. Increasing the strength of the external magnetic field enhances the domain wall resistance. In providing spintronic devices based on magnetic nanomaterials, considering and controlling the effect of domain wall on resistivity are essential.

  20. Cellulose binding domain proteins

    DOEpatents

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.; Doi, R.

    1998-11-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  1. Cellulose binding domain proteins

    DOEpatents

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  2. Modeling Conformational Transitions and Energetics of Ligand Binding with the Glutamate Receptor Ligand Binding Domain

    NASA Astrophysics Data System (ADS)

    Kurnikova, Maria

    2009-03-01

    Understanding of protein motion and energetics of conformational transitions is crucial to understanding protein function. The glutamate receptor ligand binding domain (GluR2 S1S2) is a two lobe protein, which binds ligand at the interface of two lobes and undergoes conformational transition. The cleft closure conformational transition of S1S2 has been implicated in gating of the ion channel formed by the transmembrane domain of the receptor. In this study we present a composite multi-faceted theoretical analysis of the detailed mechanism of this conformational transition based on rigid cluster decomposition of the protein structure [1] and identifying hydrogen bonds that are responsible for stabilizing the closed conformation [2]. Free energy of the protein reorganization upon ligand binding was calculated using combined Thermodynamic Integration (TI) and Umbrella Sampling (US) simulations [3]. Ligand -- protein interactions in the binding cleft were analyzed using Molecular Dynamics, continuum electrostatics and QM/MM models [4]. All model calculations compare well with corresponding experimental measurements. [4pt] [1] Protein Flexibility using Constraints from Molecular Dynamics Simulations T. Mamonova, B. Hespenheide, R. Straub, M. F. Thorpe, M. G. Kurnikova , Phys. Biol., 2, S137 (2005)[0pt] [2] Theoretical Study of the Glutamate Receptor Ligand Binding Domain Flexibility and Conformational Reorganization T. Mamonova, K. Speranskiy, and M. Kurnikova , Prot.: Struct., Func., Bioinf., 73,656 (2008)[0pt] [3] Energetics of the cleft closing transition and glutamate binding in the Glutamate Receptor ligand Binding Domain T. Mamonova, M. Yonkunas, and M. Kurnikova Biochemistry 47, 11077 (2008)[0pt] [4] On the Binding Determinants of the Glutamate Agonist with the Glutamate Receptor Ligand Binding Domain K. Speranskiy and M. Kurnikova Biochemistry 44, 11208 (2005)

  3. Mobile metallic domain walls in an all-in-all-out magnetic insulator

    DOE PAGES

    Ma, Eric Yue; Cui, Yong -Tao; Ueda, Kentaro; ...

    2015-10-30

    Magnetic domain walls are boundaries between regions with different configurations of the same magnetic order. In a magnetic insulator, where the magnetic order is tied to its bulk insulating property, it has been postulated that electrical properties are drastically different along the domain walls, where the order is inevitably disturbed. Here we report the discovery of highly conductive magnetic domain walls in a magnetic insulator, Nd 2Ir 2O 7, that has an unusual all-in-all-out magnetic order, via transport and spatially resolved microwave impedance microscopy. The domain walls have a virtually temperature-independent sheet resistance of ~1 kilohm per square, show smoothmore » morphology with no preferred orientation, are free from pinning by disorders, and have strong thermal and magnetic field responses that agree with expectations for all-in-all-out magnetic order.« less

  4. Crystal Structure of the Chromodomain Helicase DNA-binding Protein 1 (Chd1) DNA-binding Domain in Complex with DNA*

    PubMed Central

    Sharma, Amit; Jenkins, Katherine R.; Héroux, Annie; Bowman, Gregory D.

    2011-01-01

    Chromatin remodelers are ATP-dependent machines that dynamically alter the chromatin packaging of eukaryotic genomes by assembling, sliding, and displacing nucleosomes. The Chd1 chromatin remodeler possesses a C-terminal DNA-binding domain that is required for efficient nucleosome sliding and believed to be essential for sensing the length of DNA flanking the nucleosome core. The structure of the Chd1 DNA-binding domain was recently shown to consist of a SANT and SLIDE domain, analogous to the DNA-binding domain of the ISWI family, yet the details of how Chd1 recognized DNA were not known. Here we present the crystal structure of the Saccharomyces cerevisiae Chd1 DNA-binding domain in complex with a DNA duplex. The bound DNA duplex is straight, consistent with the preference exhibited by the Chd1 DNA-binding domain for extranucleosomal DNA. Comparison of this structure with the recently solved ISW1a DNA-binding domain bound to DNA reveals that DNA lays across each protein at a distinct angle, yet contacts similar surfaces on the SANT and SLIDE domains. In contrast to the minor groove binding seen for Isw1 and predicted for Chd1, the SLIDE domain of the Chd1 DNA-binding domain contacts the DNA major groove. The majority of direct contacts with the phosphate backbone occur only on one DNA strand, suggesting that Chd1 may not strongly discriminate between major and minor grooves. PMID:22033927

  5. QCD axion dark matter from long-lived domain walls during matter domination

    NASA Astrophysics Data System (ADS)

    Harigaya, Keisuke; Kawasaki, Masahiro

    2018-07-01

    The domain wall problem of the Peccei-Quinn mechanism can be solved if the Peccei-Quinn symmetry is explicitly broken by a small amount. Domain walls decay into axions, which may account for dark matter of the universe. This scheme is however strongly constrained by overproduction of axions unless the phase of the explicit breaking term is tuned. We investigate the case where the universe is matter-dominated around the temperature of the MeV scale and domain walls decay during this matter dominated epoch. We show how the viable parameter space is expanded.

  6. Neurosteroid binding to the amino terminal and glutamate binding domains of ionotropic glutamate receptors.

    PubMed

    Cameron, Krasnodara; Bartle, Emily; Roark, Ryan; Fanelli, David; Pham, Melissa; Pollard, Beth; Borkowski, Brian; Rhoads, Sarah; Kim, Joon; Rocha, Monica; Kahlson, Martha; Kangala, Melinda; Gentile, Lisa

    2012-06-01

    The endogenous neurosteroids, pregnenolone sulfate (PS) and 3α-hydroxy-5β-pregnan-20-one sulfate (PREGAS), have been shown to differentially regulate the ionotropic glutamate receptor (iGluR) family of ligand-gated ion channels. Upon binding to these receptors, PREGAS decreases current flow through the channels. Upon binding to non-NMDA or NMDA receptors containing an GluN2C or GluN2D subunit, PS also decreases current flow through the channels, however, upon binding to NMDA receptors containing an GluN2A or GluN2B subunit, flow through the channels increases. To begin to understand this differential regulation, we have cloned the S1S2 and amino terminal domains (ATD) of the NMDA GluN2B and GluN2D and AMPA GluA2 subunits. Here we present results that show that PS and PREGAS bind to different sites in the ATD of the GluA2 subunit, which when combined with previous results from our lab, now identifies two binding domains for each neurosteroid. We also show both neurosteroids bind only to the ATD of the GluN2D subunit, suggesting that this binding is distinct from that of the AMPA GluA2 subunit, with both leading to iGluR inhibition. Finally, we provide evidence that both PS and PREGAS bind to the S1S2 domain of the NMDA GluN2B subunit. Neurosteroid binding to the S1S2 domain of NMDA subunits responsible for potentiation of iGluRs and to the ATD of NMDA subunits responsible for inhibition of iGluRs, provides an interesting option for therapeutic design. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Subatomic movements of a domain wall in the Peierls potential.

    PubMed

    Novoselov, K S; Geim, A K; Dubonos, S V; Hill, E W; Grigorieva, I V

    2003-12-18

    The discrete nature of crystal lattices plays a role in virtually every material property. But it is only when the size of entities hosted by a crystal becomes comparable to the lattice period--as occurs for dislocations, vortices in superconductors and domain walls--that this discreteness is manifest explicitly. The associated phenomena are usually described in terms of a background Peierls 'atomic washboard' energy potential, which was first introduced for the case of dislocation motion in the 1940s. This concept has subsequently been invoked in many situations to describe certain features in the bulk behaviour of materials, but has to date eluded direct detection and experimental scrutiny at a microscopic level. Here we report observations of the motion of a single magnetic domain wall at the scale of the individual peaks and troughs of the atomic energy landscape. Our experiments reveal that domain walls can become trapped between crystalline planes, and that they propagate by distinct jumps that match the lattice periodicity. The jumps between valleys are found to involve unusual dynamics that shed light on the microscopic processes underlying domain-wall propagation. Such observations offer a means for probing experimentally the physics of topological defects in discrete lattices--a field rich in phenomena that have been subject to extensive theoretical study.

  8. The CWB2 Cell Wall-Anchoring Module Is Revealed by the Crystal Structures of the Clostridium difficile Cell Wall Proteins Cwp8 and Cwp6.

    PubMed

    Usenik, Aleksandra; Renko, Miha; Mihelič, Marko; Lindič, Nataša; Borišek, Jure; Perdih, Andrej; Pretnar, Gregor; Müller, Uwe; Turk, Dušan

    2017-03-07

    Bacterial cell wall proteins play crucial roles in cell survival, growth, and environmental interactions. In Gram-positive bacteria, cell wall proteins include several types that are non-covalently attached via cell wall binding domains. Of the two conserved surface-layer (S-layer)-anchoring modules composed of three tandem SLH or CWB2 domains, the latter have so far eluded structural insight. The crystal structures of Cwp8 and Cwp6 reveal multi-domain proteins, each containing an embedded CWB2 module. It consists of a triangular trimer of Rossmann-fold CWB2 domains, a feature common to 29 cell wall proteins in Clostridium difficile 630. The structural basis of the intact module fold necessary for its binding to the cell wall is revealed. A comparison with previously reported atomic force microscopy data of S-layers suggests that C. difficile S-layers are complex oligomeric structures, likely composed of several different proteins. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Controlling depinning and propagation of single domain-walls in magnetic microwires

    NASA Astrophysics Data System (ADS)

    Jiménez, Alejandro; del Real, Rafael P.; Vázquez, Manuel

    2013-03-01

    The magnetization reversal in magnetostrictive amorphous microwires takes place by depinning and propagation of a single domain wall. This is a consequence of the particular domain structure determined by the strong uniaxial anisotropy from the reinforcement of magnetoelastic and shape contributions. In the present study, after an overview on the current state-of-the art on the topic, we introduce the general behaviour of single walls in 30 to 40 cm long Fe-base microwires propagating under homogeneous field. Depending on the way the walls are generated, we distinguish among three different walls namely, standard wall, DWst, depinned and propagating from the wire's end under homogeneous field which motion is the first one to switch on; reverse wall, DWrev, propagating from the opposite end under non-homogeneous field, and defect wall, DWdef, nucleated around local defect. Both, DWrev and DWdef are observed only under large enough applied field. In the subsequent section, we study the propagation of a wall under applied field smaller than the switching field. There, we conclude that a minimum field, Hdep,0, is needed to depin the DWst, as well as that a minimum field, Hprop,0, is required for the wall to propagate long distances. In the last section, we analyse the shape of induced signals in the pickup coils upon the crossing of the walls and its correlation to the domain walls shape. We conclude that length and shape of the wall are significantly distorted by the fact that the wall is typically as long as the measuring coils. Contribution to the Topical Issue "New Trends in Magnetism and Magnetic Materials", edited by Francesca Casoli, Massimo Solzi and Paola Tiberto.

  10. Scaling properties of multitension domain wall networks

    NASA Astrophysics Data System (ADS)

    Oliveira, M. F.; Martins, C. J. A. P.

    2015-02-01

    We study the asymptotic scaling properties of domain wall networks with three different tensions in various cosmological epochs. We discuss the conditions under which a scale-invariant evolution of the network (which is well established for simpler walls) still applies and also consider the limiting case where defects are locally planar and the curvature is concentrated in the junctions. We present detailed quantitative predictions for scaling densities in various contexts, which should be testable by means of future high-resolution numerical simulations.

  11. Evolution of thick domain walls in de Sitter universe

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

    Dolgov, A.D.; Godunov, S.I.; Rudenko, A.S., E-mail: dolgov@fe.infn.it, E-mail: sgodunov@itep.ru, E-mail: a.s.rudenko@inp.nsk.su

    We consider thick domain walls in a de Sitter universe following paper by Basu and Vilenkin. However, we are interested not only in stationary solutions found therein, but also investigate the general case of domain wall evolution with time. When the wall thickness parameter, δ{sub 0}, is smaller than H {sup −1}/√2, where H is the Hubble parameter in de Sitter space-time, then the stationary solutions exist, and initial field configurations tend with time to the stationary ones. However, there are no stationary solutions for δ{sub 0} ≥ H {sup −1}/√2. We have calculated numerically the rate of the wallmore » expansion in this case and have found that the width of the wall grows exponentially fast for δ{sub 0} >> H {sup −1}. An explanation for the critical value δ{sub 0} {sub c} = H {sup −1}/√2 is also proposed.« less

  12. The extracellular protein factor Epf from Streptococcus pyogenes is a cell surface adhesin that binds to cells through an N-terminal domain containing a carbohydrate-binding module.

    PubMed

    Linke, Christian; Siemens, Nikolai; Oehmcke, Sonja; Radjainia, Mazdak; Law, Ruby H P; Whisstock, James C; Baker, Edward N; Kreikemeyer, Bernd

    2012-11-02

    Streptococcus pyogenes is an exclusively human pathogen. Streptococcal attachment to and entry into epithelial cells is a prerequisite for a successful infection of the human host and requires adhesins. Here, we demonstrate that the multidomain protein Epf from S. pyogenes serotype M49 is a streptococcal adhesin. An epf-deficient mutant showed significantly decreased adhesion to and internalization into human keratinocytes. Cell adhesion is mediated by the N-terminal domain of Epf (EpfN) and increased by the human plasma protein plasminogen. The crystal structure of EpfN, solved at 1.6 Å resolution, shows that it consists of two subdomains: a carbohydrate-binding module and a fibronectin type III domain. Both fold types commonly participate in ligand receptor and protein-protein interactions. EpfN is followed by 18 repeats of a domain classified as DUF1542 (domain of unknown function 1542) and a C-terminal cell wall sorting signal. The DUF1542 repeats are not involved in adhesion, but biophysical studies show they are predominantly α-helical and form a fiber-like stalk of tandem DUF1542 domains. Epf thus conforms with the widespread family of adhesins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), in which a cell wall-attached stalk enables long range interactions via its adhesive N-terminal domain.

  13. Annihilation of Domain Walls in a Ferromagnetic Wire

    NASA Astrophysics Data System (ADS)

    Ghosh, Anirban; Huang, Kevin; Tchernyshyov, Oleg

    We study the annihilation of topological solitons in one of the simplest systems that support them: a one-dimensional ferromagnetic wire with an easy axis along its length. In the presence of energy dissipation due to viscous losses, two solitons (domain walls) on the wire, when released from afar, approach each other and eventually annihilate to create a uniformly magnetized state. Starting from a class of exact solutions for stationary two-domain-wall configurations in the absence of dissipation, we develop an effective theory that describes this annihilation in terms of four collective coordinates: a) the two zero modes corresponding to the location of the center and the average azimuthal angle of the full structure and b) their two conjugate momenta which describe the relative twist and the relative separation of the two domain walls respectively. Comparison with micromagnetic simulation on OOOMF confirms that this theory captures well the essential physics of the process. We believe this work will be a good starting point for studying the annihilation of more complicated topological solitons like vortices and skyrmions in ferromagnetic thin films. This work is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering under Award DE-FG02-08ER46544.

  14. Mobile metallic domain walls in an all-in-all-out magnetic insulator.

    PubMed

    Ma, Eric Yue; Cui, Yong-Tao; Ueda, Kentaro; Tang, Shujie; Chen, Kai; Tamura, Nobumichi; Wu, Phillip M; Fujioka, Jun; Tokura, Yoshinori; Shen, Zhi-Xun

    2015-10-30

    Magnetic domain walls are boundaries between regions with different configurations of the same magnetic order. In a magnetic insulator, where the magnetic order is tied to its bulk insulating property, it has been postulated that electrical properties are drastically different along the domain walls, where the order is inevitably disturbed. Here we report the discovery of highly conductive magnetic domain walls in a magnetic insulator, Nd2Ir2O7, that has an unusual all-in-all-out magnetic order, via transport and spatially resolved microwave impedance microscopy. The domain walls have a virtually temperature-independent sheet resistance of ~1 kilohm per square, show smooth morphology with no preferred orientation, are free from pinning by disorders, and have strong thermal and magnetic field responses that agree with expectations for all-in-all-out magnetic order. Copyright © 2015, American Association for the Advancement of Science.

  15. Magnetoresistance of non-180° domain wall in the presence of electron-photon interaction

    NASA Astrophysics Data System (ADS)

    Majidi, Roya

    2013-04-01

    In the present paper, influence of photon on resistance of non-180° domain wall in metallic magnetic nanowires has been studied using the semiclassical approach. The analysis has been based on the Boltzmann transport equation, within the relaxation time approximation. The one-dimensional Néel-type domain wall between two ferromagnetic domains with relative magnetization angle less than 180° is considered. By increasing this angle, the contribution of the domain wall in the resistivity of the nanowire becomes considerable. It is also found that the fundamental contribution of the domain wall in resistivity can be controlled by propagating photon. These results are valuable in designing spintronic devices based on magnetic nanowires.

  16. Magnon-induced non-Markovian friction of a domain wall in a ferromagnet

    NASA Astrophysics Data System (ADS)

    Kim, Se Kwon; Tchernyshyov, Oleg; Galitski, Victor; Tserkovnyak, Yaroslav

    2018-05-01

    Motivated by the recent study on the quasiparticle-induced friction of solitons in superfluids, we theoretically study magnon-induced intrinsic friction of a domain wall in a one-dimensional ferromagnet. To this end, we start by obtaining the hitherto overlooked dissipative interaction of a domain wall and its quantum magnon bath to linear order in the domain-wall velocity and to quadratic order in magnon fields. An exact expression for the pertinent scattering matrix is obtained with the aid of supersymmetric quantum mechanics. We then derive the magnon-induced frictional force on a domain wall in two different frameworks: time-dependent perturbation theory in quantum mechanics and the Keldysh formalism, which yield identical results. The latter, in particular, allows us to verify the fluctuation-dissipation theorem explicitly by providing both the frictional force and the correlator of the associated stochastic Langevin force. The potential for magnons induced by a domain wall is reflectionless, and thus the resultant frictional force is non-Markovian similar to the case of solitons in superfluids. They share an intriguing connection to the Abraham-Lorentz force that is well known for its causality paradox. The dynamical responses of a domain wall are studied under a few simple circumstances, where the non-Markovian nature of the frictional force can be probed experimentally. Our work, in conjunction with the previous study on solitons in superfluids, shows that the macroscopic frictional force on solitons can serve as an effective probe of the microscopic degrees of freedom of the system.

  17. Free-electron gas at charged domain walls in insulating BaTiO3

    PubMed Central

    Sluka, Tomas; Tagantsev, Alexander K.; Bednyakov, Petr; Setter, Nava

    2013-01-01

    Hetero interfaces between metal-oxides display pronounced phenomena such as semiconductor-metal transitions, magnetoresistance, the quantum hall effect and superconductivity. Similar effects at compositionally homogeneous interfaces including ferroic domain walls are expected. Unlike hetero interfaces, domain walls can be created, displaced, annihilated and recreated inside a functioning device. Theory predicts the existence of 'strongly' charged domain walls that break polarization continuity, but are stable and conduct steadily through a quasi-two-dimensional electron gas. Here we show this phenomenon experimentally in charged domain walls of the prototypical ferroelectric BaTiO3. Their steady metallic-type conductivity, 109 times that of the parent matrix, evidence the presence of stable degenerate electron gas, thus adding mobility to functional interfaces. PMID:23651996

  18. Annealing effect on current-driven domain wall motion in Pt/[Co/Ni] wire

    NASA Astrophysics Data System (ADS)

    Furuta, Masaki; Liu, Yang; Sepehri-Amin, Hossein; Hono, Kazuhiro; Zhu, Jian-Gang Jimmy

    2017-09-01

    The annealing effect on the efficiency of current-driven domain wall motion governed by the spin Hall effect in perpendicularly magnetized Pt/[Co/Ni] wires is investigated experimentally. Important physical parameters, such as the Dzyaloshinskii-Moriya Interaction (DMI), spin Hall angle, and perpendicular anisotropy field strength, for the domain wall motion are all characterized at each annealing temperature. It is found that annealing of wires at temperatures over 120 °C causes significant reduction of the domain wall velocity. Energy dispersive X-ray spectroscopy analysis shows pronounced Co diffusion across the Pt/Co interface resulted from annealing at relatively high temperatures. The combined modeling study shows that the reduction of DMI caused by annealing is mostly responsible for the domain wall velocity reduction due to annealing.

  19. Thermal-induced domain wall motion of tip-inverted micro/nanodomains in near-stoichiometric LiNbO3 crystals

    NASA Astrophysics Data System (ADS)

    Liu, X. Y.; Kitamura, K.; Liu, Y. M.; Ohuchi, F. S.; Li, J. Y.

    2011-09-01

    Thermal-induced domain wall motion of tip-inverted micro/nanodomains in near-stoichiometric LiNbO3 single crystals was investigated using piezoresponse force microscopy (PFM). The domain wall motion was observed in PFM phase and amplitude images at room temperature after the sample was subjected to a thermal process at a heating temperature higher than 100 °C. In hexagonal domains with only y walls, predetermined nucleation with layer-by-layer growth is the main mechanism for the domain wall motion. In the domains composed of both x walls and y walls, the x walls are more mobile than the y walls, and the domain wall motion starts from the random nucleation of steps along the x walls that finally grow into y walls. The domain wall motion in the near-stoichiometric LiNbO3 crystal is attributed to the energy-preferable domain wall orientation, the pyroelectric effect, and the screening charge variation caused by the thermal process.

  20. Big domains are novel Ca²+-binding modules: evidences from big domains of Leptospira immunoglobulin-like (Lig) proteins.

    PubMed

    Raman, Rajeev; Rajanikanth, V; Palaniappan, Raghavan U M; Lin, Yi-Pin; He, Hongxuan; McDonough, Sean P; Sharma, Yogendra; Chang, Yung-Fu

    2010-12-29

    Many bacterial surface exposed proteins mediate the host-pathogen interaction more effectively in the presence of Ca²+. Leptospiral immunoglobulin-like (Lig) proteins, LigA and LigB, are surface exposed proteins containing Bacterial immunoglobulin like (Big) domains. The function of proteins which contain Big fold is not known. Based on the possible similarities of immunoglobulin and βγ-crystallin folds, we here explore the important question whether Ca²+ binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. We selected six individual Big domains for this study (three from the conserved part of LigA and LigB, denoted as Lig A3, Lig A4, and LigBCon5; two from the variable region of LigA, i.e., 9(th) (Lig A9) and 10(th) repeats (Lig A10); and one from the variable region of LigB, i.e., LigBCen2. We have also studied the conserved region covering the three and six repeats (LigBCon1-3 and LigCon). All these proteins bind the calcium-mimic dye Stains-all. All the selected four domains bind Ca²+ with dissociation constants of 2-4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm), probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. We demonstrate that the Lig are Ca²+-binding proteins, with Big domains harbouring the binding motif. We conclude that despite differences in sequence, a Big motif binds Ca²+. This work thus sets up a strong possibility for classifying the proteins containing Big domains as a novel family of Ca²+-binding proteins. Since Big domain is a part of many proteins in bacterial kingdom, we suggest a possible function these proteins via Ca²+ binding.

  1. Gapped fermionic spectrum from a domain wall in seven dimension

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Subir; Rai, Nishal

    2018-05-01

    We obtain a domain wall solution in maximally gauged seven dimensional supergravity, which interpolates between two AdS spaces and spontaneously breaks a U (1) symmetry. We analyse frequency dependence of conductivity and find power law behaviour at low frequency. We consider certain fermions of supergravity in the background of this domain wall and compute holographic spectral function of the operators in the dual six dimensional theory. We find fermionic operators involving bosons with non-zero expectation value lead to gapped spectrum.

  2. Local and global gravitational aspects of domain wall space-times

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

    Cvetic, M.; Griffies, S.; Soleng, H.H.

    1993-09-15

    Local and global gravitational effects induced by eternal vacuum domain walls are studied. We concentrate on thin walls between nonequal and nonpositive cosmological constants on each side of the wall. The assumption of homogeneity, isotropy, and geodesic completeness of the space-time intrinsic to the wall as described in the comoving coordinate system and the constraint that the same symmetries hold in hypersurfaces parallel to the wall yield a general [ital Ansatz] for the line element of space-time. We restrict the problem further by demanding that the wall's surface energy density, [sigma], is positive and by requiring that the infinitely thinmore » wall represents a thin-wall limit of kinklike scalar field configuration. These vacuum domain walls fall in three classes depending on the value of their [sigma]: (1) extreme walls with [sigma]=[sigma][sub ext] are planar, static walls corresponding to supersymmetric configurations, (2) nonextreme walls with [sigma]=[sigma][sub non][gt][sigma][sub ext] correspond to expanding bubbles with observers on either side of the wall being [ital inside] the bubble, and (3) ultraextreme walls with [sigma]=[sigma][sub ultra][lt][sigma][sub ext] represent the bubbles of false vacuum decay. On the sides with less negative cosmological constant, the extreme, nonextreme, and ultraextreme walls exhibit no, repulsive, and attractive effective gravitational forces,'' respectively. These gravitational forces'' are global effects not caused by local curvature. Since the nonextreme wall encloses observers on both sides, the supersymmetric system has the lowest gravitational mass accessible to outside observers. It is conjectured that similar positive mass protection occurs in all physical systems and that no finite negative mass object can exist inside the universe.« less

  3. Elucidation of the binding preferences of peptide recognition modules: SH3 and PDZ domains.

    PubMed

    Teyra, Joan; Sidhu, Sachdev S; Kim, Philip M

    2012-08-14

    Peptide-binding domains play a critical role in regulation of cellular processes by mediating protein interactions involved in signalling. In recent years, the development of large-scale technologies has enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. These efforts have provided significant insights into the binding specificities of these modular domains. Many research groups have taken advantage of this unprecedented volume of specificity data and have developed a variety of new algorithms for the prediction of binding specificities of peptide-binding domains and for the prediction of their natural binding targets. This knowledge has also been applied to the design of synthetic peptide-binding domains in order to rewire protein-protein interaction networks. Here, we describe how these experimental technologies have impacted on our understanding of peptide-binding domain specificities and on the elucidation of their natural ligands. We discuss SH3 and PDZ domains as well characterized examples, and we explore the feasibility of expanding high-throughput experiments to other peptide-binding domains. Copyright © 2012. Published by Elsevier B.V.

  4. Wall mechanics and exocytosis define the shape of growth domains in fission yeast.

    PubMed

    Abenza, Juan F; Couturier, Etienne; Dodgson, James; Dickmann, Johanna; Chessel, Anatole; Dumais, Jacques; Carazo Salas, Rafael E

    2015-10-12

    The amazing structural variety of cells is matched only by their functional diversity, and reflects the complex interplay between biochemical and mechanical regulation. How both regulatory layers generate specifically shaped cellular domains is not fully understood. Here, we report how cell growth domains are shaped in fission yeast. Based on quantitative analysis of cell wall expansion and elasticity, we develop a model for how mechanics and cell wall assembly interact and use it to look for factors underpinning growth domain morphogenesis. Surprisingly, we find that neither the global cell shape regulators Cdc42-Scd1-Scd2 nor the major cell wall synthesis regulators Bgs1-Bgs4-Rgf1 are reliable predictors of growth domain geometry. Instead, their geometry can be defined by cell wall mechanics and the cortical localization pattern of the exocytic factors Sec6-Syb1-Exo70. Forceful re-directioning of exocytic vesicle fusion to broader cortical areas induces proportional shape changes to growth domains, demonstrating that both features are causally linked.

  5. Magnetoconductance signatures of chiral domain-wall bound states in magnetic topological insulators

    NASA Astrophysics Data System (ADS)

    Tiwari, Kunal L.; Coish, W. A.; Pereg-Barnea, T.

    2017-12-01

    Recent magnetoconductance measurements performed on magnetic topological insulator candidates have revealed butterfly-shaped hysteresis. This hysteresis has been attributed to the formation of gapless chiral domain-wall bound states during a magnetic-field sweep. We treat this phenomenon theoretically, providing a link between microscopic magnetization dynamics and butterfly hysteresis in magnetoconductance. Further, we illustrate how a spatially resolved conductance measurement can probe the most striking feature of the domain-wall bound states: their chirality. This work establishes a regime where a definitive link between butterfly hysteresis in longitudinal magneto-conductance and domain-wall bound states can be made. This analysis provides an important tool for the identification of magnetic topological insulators.

  6. Enhanced spin transfer torque effect for transverse domain walls in cylindrical nanowires

    NASA Astrophysics Data System (ADS)

    Franchin, Matteo; Knittel, Andreas; Albert, Maximilian; Chernyshenko, Dmitri S.; Fischbacher, Thomas; Prabhakar, Anil; Fangohr, Hans

    2011-09-01

    Recent studies have predicted extraordinary properties for transverse domain walls in cylindrical nanowires: zero depinning current, the absence of the Walker breakdown, and applications as domain wall oscillators. In order to reliably control the domain wall motion, it is important to understand how they interact with pinning centers, which may be engineered, for example, through modulations in the nanowire geometry (such as notches or extrusions) or in the magnetic properties of the material. In this paper we study the motion and depinning of transverse domain walls through pinning centers in ferromagnetic cylindrical nanowires. We use (i) magnetic fields and (ii) spin-polarized currents to drive the domain walls along the wire. The pinning centers are modelled as a section of the nanowire which exhibits a uniaxial crystal anisotropy where the anisotropy easy axis and the wire axis enclose a variable angle θP. Using (i) magnetic fields, we find that the minimum and the maximum fields required to push the domain wall through the pinning center differ by 30%. On the contrary, using (ii) spin-polarized currents, we find variations of a factor 130 between the minimum value of the depinning current density (observed for θP=0∘, i.e., anisotropy axis pointing parallel to the wire axis) and the maximum value (for θP=90∘, i.e., anisotropy axis perpendicular to the wire axis). We study the depinning current density as a function of the height of the energy barrier of the pinning center using numerical and analytical methods. We find that for an industry standard energy barrier of 40kBT, a depinning current of about 5μA (corresponding to a current density of 6×1010A/m2 in a nanowire of 10nm diameter) is sufficient to depin the domain wall. We reveal and explain the mechanism that leads to these unusually low depinning currents. One requirement for this depinning mechanism is for the domain wall to be able to rotate around its own axis. With the right barrier design

  7. SH2 Domains Serve as Lipid-Binding Modules for pTyr-Signaling Proteins.

    PubMed

    Park, Mi-Jeong; Sheng, Ren; Silkov, Antonina; Jung, Da-Jung; Wang, Zhi-Gang; Xin, Yao; Kim, Hyunjin; Thiagarajan-Rosenkranz, Pallavi; Song, Seohyeon; Yoon, Youngdae; Nam, Wonhee; Kim, Ilshin; Kim, Eui; Lee, Dong-Gyu; Chen, Yong; Singaram, Indira; Wang, Li; Jang, Myoung Ho; Hwang, Cheol-Sang; Honig, Barry; Ryu, Sungho; Lorieau, Justin; Kim, You-Me; Cho, Wonhwa

    2016-04-07

    The Src-homology 2 (SH2) domain is a protein interaction domain that directs myriad phosphotyrosine (pY)-signaling pathways. Genome-wide screening of human SH2 domains reveals that ∼90% of SH2 domains bind plasma membrane lipids and many have high phosphoinositide specificity. They bind lipids using surface cationic patches separate from pY-binding pockets, thus binding lipids and the pY motif independently. The patches form grooves for specific lipid headgroup recognition or flat surfaces for non-specific membrane binding and both types of interaction are important for cellular function and regulation of SH2 domain-containing proteins. Cellular studies with ZAP70 showed that multiple lipids bind its C-terminal SH2 domain in a spatiotemporally specific manner and thereby exert exquisite spatiotemporal control over its protein binding and signaling activities in T cells. Collectively, this study reveals how lipids control SH2 domain-mediated cellular protein-protein interaction networks and suggest a new strategy for therapeutic modulation of pY-signaling pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Identification and functional characterization of an Src homology domain 3 domain-binding site on Cbl.

    PubMed

    Sanjay, Archana; Miyazaki, Tsuyoshi; Itzstein, Cecile; Purev, Enkhtsetseg; Horne, William C; Baron, Roland

    2006-12-01

    Cbl is an adaptor protein and ubiquitin ligase that binds and is phosphorylated by the nonreceptor tyrosine kinase Src. We previously showed that the primary interaction between Src and Cbl is mediated by the Src homology domain 3 (SH3) of Src binding to proline-rich sequences of Cbl. The peptide Cbl RDLPPPPPPDRP(540-551), which corresponds to residues 540-551 of Cbl, inhibited the binding of a GST-Src SH3 fusion protein to Cbl, whereas RDLAPPAPPPDR(540-551) did not, suggesting that Src binds to this site on Cbl in a class I orientation. Mutating prolines 543-548 reduced Src binding to the Cbl 479-636 fragment significantly more than mutating the prolines in the PPVPPR(494-499) motif, which was previously reported to bind Src SH3. Mutating Cbl prolines 543-548 to alanines substantially reduced Src binding to Cbl, Src-induced phosphorylation of Cbl, and the inhibition of Src kinase activity by Cbl. Expressing the mutated Cbl in osteoclasts induced a moderate reduction in bone-resorbing activity and increased amounts of Src protein. In contrast, disabling the tyrosine kinase-binding domain of full-length Cbl by mutating glycine 306 to glutamic acid, and thereby preventing the previously described binding of the tyrosine kinase-binding domain to the Src phosphotyrosine 416, had no effect on Cbl phosphorylation, the inhibition of Src activity by full-length Cbl, or bone resorption. These data indicate that the Cbl RDLPPPP(540-546) sequence is a functionally important binding site for Src.

  9. The influence of annealing on domain wall propagation in bistable amorphous microwire with unidirectional effect

    NASA Astrophysics Data System (ADS)

    Onufer, Jozef; Ziman, Ján; Duranka, Peter; Kladivová, Mária

    2018-07-01

    The effect of gradual annealing on the domain wall mobility (velocity), nucleation, critical depinning and propagation fields in amorphous FeSiB microwires has been studied. A new experimental set-up, presented in this paper, allows measurement of average domain wall velocity for four different conditions and detection of the presence of unidirectional effect in wall propagation without manipulation of the microwire. The proposed interpretation is that a domain wall is considered as a relatively long object which can change its axial dimension due to inhomogeneity of damping forces acting on the wall during its propagation. It is demonstrated that unidirectional effect in domain wall propagation can be strongly reduced by annealing the wire at temperatures higher than 350 °C.

  10. Construction of a Functional S-Layer Fusion Protein Comprising an Immunoglobulin G-Binding Domain for Development of Specific Adsorbents for Extracorporeal Blood Purification

    PubMed Central

    Völlenkle, Christine; Weigert, Stefan; Ilk, Nicola; Egelseer, Eva; Weber, Viktoria; Loth, Fritz; Falkenhagen, Dieter; Sleytr, Uwe B.; Sára, Margit

    2004-01-01

    The chimeric gene encoding a C-terminally-truncated form of the S-layer protein SbpA from Bacillus sphaericus CCM 2177 and two copies of the Fc-binding Z-domain was constructed, cloned, and heterologously expressed in Escherichia coli HMS174(DE3). The Z-domain is a synthetic analogue of the B-domain of protein A, capable of binding the Fc part of immunoglobulin G (IgG). The S-layer fusion protein rSbpA31-1068/ZZ retained the specific properties of the S-layer protein moiety to self-assemble in suspension and to recrystallize on supports precoated with secondary cell wall polymer (SCWP), which is the natural anchoring molecule for the S-layer protein in the bacterial cell wall. Due to the construction principle of the S-layer fusion protein, the ZZ-domains remained exposed on the outermost surface of the protein lattice. The binding capacity of the native or cross-linked monolayer for human IgG was determined by surface plasmon resonance measurements. For batch adsorption experiments, 3-μm-diameter, biocompatible cellulose-based, SCWP-coated microbeads were used for recrystallization of the S-layer fusion protein. In the case of the native monolayer, the binding capacity for human IgG was 5.1 ng/mm2, whereas after cross-linking with dimethyl pimelimidate, 4.4 ng of IgG/mm2 was bound. This corresponded to 78 and 65% of the theoretical saturation capacity of a planar surface for IgGs aligned in the upright position, respectively. Compared to commercial particles used as immunoadsorbents to remove autoantibodies from sera of patients suffering from an autoimmune disease, the IgG binding capacity of the S-layer fusion protein-coated microbeads was at least 20 times higher. For that reason, this novel type of microbeads should find application in the microsphere-based detoxification system. PMID:15006773

  11. Domain wall magnetoresistance in BiFeO3 thin films measured by scanning probe microscopy

    NASA Astrophysics Data System (ADS)

    Domingo, N.; Farokhipoor, S.; Santiso, J.; Noheda, B.; Catalan, G.

    2017-08-01

    We measure the magnetotransport properties of individual 71° domain walls in multiferroic BiFeO3 by means of conductive—atomic force microscopy (C-AFM) in the presence of magnetic fields up to one Tesla. The results suggest anisotropic magnetoresistance at room temperature, with the sign of the magnetoresistance depending on the relative orientation between the magnetic field and the domain wall plane. A consequence of this finding is that macroscopically averaged magnetoresistance measurements for domain wall bunches are likely to underestimate the magnetoresistance of each individual domain wall.

  12. Electric-field control of magnetic domain-wall velocity in ultrathin cobalt with perpendicular magnetization.

    PubMed

    Chiba, D; Kawaguchi, M; Fukami, S; Ishiwata, N; Shimamura, K; Kobayashi, K; Ono, T

    2012-06-06

    Controlling the displacement of a magnetic domain wall is potentially useful for information processing in magnetic non-volatile memories and logic devices. A magnetic domain wall can be moved by applying an external magnetic field and/or electric current, and its velocity depends on their magnitudes. Here we show that the applying an electric field can change the velocity of a magnetic domain wall significantly. A field-effect device, consisting of a top-gate electrode, a dielectric insulator layer, and a wire-shaped ferromagnetic Co/Pt thin layer with perpendicular anisotropy, was used to observe it in a finite magnetic field. We found that the application of the electric fields in the range of ± 2-3 MV cm(-1) can change the magnetic domain wall velocity in its creep regime (10(6)-10(3) m s(-1)) by more than an order of magnitude. This significant change is due to electrical modulation of the energy barrier for the magnetic domain wall motion.

  13. Ligand-Binding Properties and Conformational Dynamics of Autolysin Repeat Domains in Staphylococcal Cell Wall Recognition

    PubMed Central

    Zoll, Sebastian; Schlag, Martin; Shkumatov, Alexander V.; Rautenberg, Maren; Svergun, Dmitri I.; Götz, Friedrich

    2012-01-01

    The bifunctional major autolysin Atl plays a key role in staphylococcal cell separation. Processing of Atl yields catalytically active amidase (AM) and glucosaminidase (GL) domains that are each fused to repeating units. The two repeats of AM (R1 and R2) target the enzyme to the septum, where it cleaves murein between dividing cells. We have determined the crystal structure of R2, which reveals that each repeat folds into two half-open β-barrel subunits. We further demonstrate that lipoteichoic acid serves as a receptor for the repeats and that this interaction depends on conserved surfaces in each subunit. Small-angle X-ray scattering of the mature amidase reveals the presence of flexible linkers separating the AM, R1, and R2 units. Different levels of flexibility for each linker provide mechanistic insights into the conformational dynamics of the full-length protein and the roles of its components in cell wall association and catalysis. Our analysis supports a model in which the repeats direct the catalytic AM domain to the septum, where it can optimally perform the final step of cell division. PMID:22609916

  14. Proposal for a Domain Wall Nano-Oscillator driven by Non-uniform Spin Currents

    PubMed Central

    Sharma, Sanchar; Muralidharan, Bhaskaran; Tulapurkar, Ashwin

    2015-01-01

    We propose a new mechanism and a related device concept for a robust, magnetic field tunable radio-frequency (rf) oscillator using the self oscillation of a magnetic domain wall subject to a uniform static magnetic field and a spatially non-uniform vertical dc spin current. The self oscillation of the domain wall is created as it translates periodically between two unstable positions, one being in the region where both the dc spin current and the magnetic field are present, and the other, being where only the magnetic field is present. The vertical dc spin current pushes it away from one unstable position while the magnetic field pushes it away from the other. We show that such oscillations are stable under noise and can exhibit a quality factor of over 1000. A domain wall under dynamic translation, not only being a source for rich physics, is also a promising candidate for advancements in nanoelectronics with the actively researched racetrack memory architecture, digital and analog switching paradigms as candidate examples. Devising a stable rf oscillator using a domain wall is hence another step towards the realization of an all domain wall logic scheme. PMID:26420544

  15. Evaluation of Selected Binding Domains for the Analysis of Ubiquitinated Proteomes

    NASA Astrophysics Data System (ADS)

    Nakayasu, Ernesto S.; Ansong, Charles; Brown, Joseph N.; Yang, Feng; Lopez-Ferrer, Daniel; Qian, Wei-Jun; Smith, Richard D.; Adkins, Joshua N.

    2013-08-01

    Ubiquitination is an abundant post-translational modification that consists of covalent attachment of ubiquitin to lysine residues or the N-terminus of proteins. Mono- and polyubiquitination have been shown to be involved in many critical eukaryotic cellular functions and are often disrupted by intracellular bacterial pathogens. Affinity enrichment of ubiquitinated proteins enables global analysis of this key modification. In this context, the use of ubiquitin-binding domains is a promising but relatively unexplored alternative to more broadly used immunoaffinity or tagged affinity enrichment methods. In this study, we evaluated the application of eight ubiquitin-binding domains that have differing affinities for ubiquitination states. Small-scale proteomics analysis identified ~200 ubiquitinated protein candidates per ubiquitin-binding domain pull-down experiment. Results from subsequent Western blot analyses that employed anti-ubiquitin or monoclonal antibodies against polyubiquitination at lysine 48 and 63 suggest that ubiquitin-binding domains from Dsk2 and ubiquilin-1 have the broadest specificity in that they captured most types of ubiquitination, whereas the binding domain from NBR1 was more selective to polyubiquitination. These data demonstrate that with optimized purification conditions, ubiquitin-binding domains can be an alternative tool for proteomic applications. This approach is especially promising for the analysis of tissues or cells resistant to transfection, of which the overexpression of tagged ubiquitin is a major hurdle.

  16. Evaluation of selected binding domains for the analysis of ubiquitinated proteomes

    PubMed Central

    Nakayasu, Ernesto S.; Ansong, Charles; Brown, Joseph N.; Yang, Feng; Lopez-Ferrer, Daniel; Qian, Wei-Jun; Smith, Richard D.; Adkins, Joshua N.

    2013-01-01

    Ubiquitination is an abundant post-translational modification that consists of covalent attachment of ubiquitin to lysine residues or the N-terminus of proteins. Mono and polyubiquitination have been shown to be involved in many critical eukaryotic cellular functions and are often disrupted by intracellular bacterial pathogens. Affinity enrichment of ubiquitinated proteins enables global analysis of this key modification. In this context, the use of ubiquitin-binding domains is a promising, but relatively unexplored alternative to more broadly used immunoaffinity or tagged affinity enrichment methods. In this study, we evaluated the application of eight ubiquitin-binding domains that have differing affinities for ubiquitination states. Small-scale proteomics analysis identified ∼200 ubiquitinated protein candidates per ubiquitin-binding domain pull-down experiment. Results from subsequent Western blot analyses that employed anti-ubiquitin or monoclonal antibodies against polyubiquitination at lysine 48 and 63 suggest that ubiquitin-binding domains from Dsk2 and ubiquilin-1 have the broadest specificity in that they captured most types of ubiquitination, whereas the binding domain from NBR1 was more selective to polyubiquitination. These data demonstrate that with optimized purification conditions, ubiquitin-binding domains can be an alternative tool for proteomic applications. This approach is especially promising for the analysis of tissues or cells resistant to transfection, of which the overexpression of tagged ubiquitin is a major hurdle. PMID:23649778

  17. Néel walls between tailored parallel-stripe domains in IrMn/CoFe exchange bias layers

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

    Ueltzhöffer, Timo, E-mail: timo.ueltzhoeffer@physik.uni-kassel.de; Schmidt, Christoph; Ehresmann, Arno

    Tailored parallel-stripe magnetic domains with antiparallel magnetizations in adjacent domains along the long stripe axis have been fabricated in an IrMn/CoFe Exchange Bias thin film system by 10 keV He{sup +}-ion bombardment induced magnetic patterning. Domain walls between these domains are of Néel type and asymmetric as they separate domains of different anisotropies. X-ray magnetic circular dichroism asymmetry images were obtained by x-ray photoelectron emission microscopy at the Co/Fe L{sub 3} edges at the synchrotron radiation source BESSY II. They revealed Néel-wall tail widths of 1 μm in agreement with the results of a model that was modified in order to describemore » such walls. Similarly obtained domain core widths show a discrepancy to values estimated from the model, but could be explained by experimental broadening. The rotation senses in adjacent walls were determined, yielding unwinding domain walls with non-interacting walls in this layer system.« less

  18. Mechanical Unfolding Studies on Single-Domain SUMO and Multi-Domain Periplasmic Binding Proteins

    NASA Astrophysics Data System (ADS)

    Kotamarthi, Hema Chandra; Ainavarapu, Sri Rama Koti

    Protein mechanics is a key component of many cellular and sub-cellular processes. The current review focuses on recent studies from our laboratory that probe the effect of sequence on the mechanical stability of structurally similar proteins and the unfolding mechanisms of multi-domain periplasmic binding proteins. Ubiquitin and small ubiquitin-related modifiers (SUMOs) are structurally similar and possess different mechanical stabilities, ubiquitin being stronger than SUMOs as revealed from their unfolding forces. These differences are plausibly due to the variation in number of inter-residue contacts. The unfolding potential widths determined from the pulling speed-dependent studies revealed that SUMOs are mechanically more flexible than ubiquitin. This flexibility of SUMOs plays a role in ligand binding and our single-molecule studies on SUMO interaction with SUMO binding motifs (SBMs) have shown that ligand binding decreases the SUMO flexibility and increases its mechanical stability. Studies on multi-domain periplasmic binding proteins have revealed that the unfolding energy landscape of these proteins is complex and they follow kinetic partitioning between two-state and multiple three-state pathways.

  19. Direct observation of interlocked domain walls and topological four-state vortex-like domain patterns in multiferroic YMnO{sub 3} single crystal

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

    Tian, Lei; School of Materials Science and Engineering, Dalian Jiaotong University, Dalian, Liaoning 116028; Wang, Yumei, E-mail: wangym@iphy.ac.cn

    2015-03-16

    Using the advanced spherical aberration-corrected high angle annular dark field scanning transmission electron microscope imaging techniques, we investigated atomic-scale structural features of domain walls and domain patterns in YMnO{sub 3} single crystal. Three different types of interlocked ferroelectric-antiphase domain walls and two abnormal topological four-state vortex-like domain patterns are identified. Each ferroelectric domain wall is accompanied by a translation vector, i.e., 1/6[210] or −1/6[210], demonstrating its interlocked nature. Different from the four-state vortex domain patterns caused by a partial edge dislocation, two four-state vortex-like domain configurations have been obtained at atomic level. These observed phenomena can further extend our understandingmore » of the fascinating vortex domain patterns in multiferroic hexagonal rare-earth manganites.« less

  20. A cellulose binding domain protein restores female fertility when expressed in transgenic Bintje potato.

    PubMed

    Jones, Richard W; Perez, Frances G

    2016-03-18

    Expression of a gene encoding the family 1 cellulose binding domain protein CBD1, identified in the cellulosic cell wall of the potato late blight pathogen Phytophthora infestans, was tested in transgenic potato to determine if it had an influence on plant cell walls and resistance to late blight. Multiple regenerants of potato (cv. Bintje) were developed and selected for high expression of CBD 1 transcripts. Tests with detached leaflets showed no evidence of increased or decreased resistance to P. infestans, in comparison with the blight susceptible Bintje controls, however, changes in plant morphology were evident in CBD 1 transgenics. Plant height increases were evident, and most importantly, the ability to produce seed berries from a previously sterile cultivar. Immunolocalization of CBD 1 in seed berries revealed the presence throughout the tissue. While Bintje control plants are male and female sterile, CBD 1 transgenics were female fertile. Crosses made using pollen from the late blight resistant Sarpo Mira and transgenic CBD1 Bintje as the female parent demonstrated the ability to introgress P. infestans targeted resistance genes, as well as genes responsible for color and tuber shape, into Bintje germplasm. A family 1 cellulose-binding domain (CBD 1) encoding gene from the potato late blight pathogen P. infestans was used to develop transgenic Bintje potato plants. Transgenic plants became female fertile, allowing for a previously sterile cultivar to be used in breeding improvement. Selection for the absence of the CBD transgene in progeny should allow for immediate use of a genetically enhanced material. Potential for use in other Solanaceous crops is proposed.

  1. Measles virus fusion machinery activated by sialic acid binding globular domain.

    PubMed

    Talekar, Aparna; Moscona, Anne; Porotto, Matteo

    2013-12-01

    Paramyxoviruses, including the human pathogen measles virus (MV) and the avian Newcastle disease virus (NDV), enter host cells through fusion of the viral envelope with the target cell membrane. This fusion is driven by the concerted action of two viral envelope glycoproteins: the receptor binding protein and the fusion protein (F). The MV receptor binding protein (hemagglutinin [H]) attaches to proteinaceous receptors on host cells, while the receptor binding protein of NDV (hemagglutinin-neuraminidase [HN]) interacts with sialic acid-containing receptors. The receptor-bound HN/H triggers F to undergo conformational changes that render it competent to mediate fusion of the viral and cellular membranes. The mechanism of fusion activation has been proposed to be different for sialic acid-binding viruses and proteinaceous receptor-binding viruses. We report that a chimeric protein containing the NDV HN receptor binding region and the MV H stalk domain can activate MV F to fuse, suggesting that the signal to the stalk of a protein-binding receptor binding molecule can be transmitted from a sialic acid binding domain. By engineering the NDV HN globular domain to interact with a proteinaceous receptor, the fusion activation signal was preserved. Our findings are consistent with a unified mechanism of fusion activation, at least for the Paramyxovirinae subfamily, in which the receptor binding domains of the receptor binding proteins are interchangeable and the stalk determines the specificity of F activation.

  2. Big Domains Are Novel Ca2+-Binding Modules: Evidences from Big Domains of Leptospira Immunoglobulin-Like (Lig) Proteins

    PubMed Central

    Palaniappan, Raghavan U. M.; Lin, Yi-Pin; He, Hongxuan; McDonough, Sean P.; Sharma, Yogendra; Chang, Yung-Fu

    2010-01-01

    Background Many bacterial surface exposed proteins mediate the host-pathogen interaction more effectively in the presence of Ca2+. Leptospiral immunoglobulin-like (Lig) proteins, LigA and LigB, are surface exposed proteins containing Bacterial immunoglobulin like (Big) domains. The function of proteins which contain Big fold is not known. Based on the possible similarities of immunoglobulin and βγ-crystallin folds, we here explore the important question whether Ca2+ binds to a Big domains, which would provide a novel functional role of the proteins containing Big fold. Principal Findings We selected six individual Big domains for this study (three from the conserved part of LigA and LigB, denoted as Lig A3, Lig A4, and LigBCon5; two from the variable region of LigA, i.e., 9th (Lig A9) and 10th repeats (Lig A10); and one from the variable region of LigB, i.e., LigBCen2. We have also studied the conserved region covering the three and six repeats (LigBCon1-3 and LigCon). All these proteins bind the calcium-mimic dye Stains-all. All the selected four domains bind Ca2+ with dissociation constants of 2–4 µM. Lig A9 and Lig A10 domains fold well with moderate thermal stability, have β-sheet conformation and form homodimers. Fluorescence spectra of Big domains show a specific doublet (at 317 and 330 nm), probably due to Trp interaction with a Phe residue. Equilibrium unfolding of selected Big domains is similar and follows a two-state model, suggesting the similarity in their fold. Conclusions We demonstrate that the Lig are Ca2+-binding proteins, with Big domains harbouring the binding motif. We conclude that despite differences in sequence, a Big motif binds Ca2+. This work thus sets up a strong possibility for classifying the proteins containing Big domains as a novel family of Ca2+-binding proteins. Since Big domain is a part of many proteins in bacterial kingdom, we suggest a possible function these proteins via Ca2+ binding. PMID:21206924

  3. The Extracellular Protein Factor Epf from Streptococcus pyogenes Is a Cell Surface Adhesin That Binds to Cells through an N-terminal Domain Containing a Carbohydrate-binding Module*

    PubMed Central

    Linke, Christian; Siemens, Nikolai; Oehmcke, Sonja; Radjainia, Mazdak; Law, Ruby H. P.; Whisstock, James C.; Baker, Edward N.; Kreikemeyer, Bernd

    2012-01-01

    Streptococcus pyogenes is an exclusively human pathogen. Streptococcal attachment to and entry into epithelial cells is a prerequisite for a successful infection of the human host and requires adhesins. Here, we demonstrate that the multidomain protein Epf from S. pyogenes serotype M49 is a streptococcal adhesin. An epf-deficient mutant showed significantly decreased adhesion to and internalization into human keratinocytes. Cell adhesion is mediated by the N-terminal domain of Epf (EpfN) and increased by the human plasma protein plasminogen. The crystal structure of EpfN, solved at 1.6 Å resolution, shows that it consists of two subdomains: a carbohydrate-binding module and a fibronectin type III domain. Both fold types commonly participate in ligand receptor and protein-protein interactions. EpfN is followed by 18 repeats of a domain classified as DUF1542 (domain of unknown function 1542) and a C-terminal cell wall sorting signal. The DUF1542 repeats are not involved in adhesion, but biophysical studies show they are predominantly α-helical and form a fiber-like stalk of tandem DUF1542 domains. Epf thus conforms with the widespread family of adhesins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), in which a cell wall-attached stalk enables long range interactions via its adhesive N-terminal domain. PMID:22977243

  4. Highly mobile ferroelastic domain walls in compositionally graded ferroelectric thin films

    DOE PAGES

    Damodaran, Anoop; Okatan, M. B.; Kacher, J.; ...

    2016-02-15

    Domains and domain walls are critical in determining the response of ferroelectrics, and the ability to controllably create, annihilate, or move domains is essential to enable a range of next-generation devices. Whereas electric-field control has been demonstrated for ferroelectric 180° domain walls, similar control of ferroelastic domains has not been achieved. Here, using controlled composition and strain gradients, we demonstrate deterministic control of ferroelastic domains that are rendered highly mobile in a controlled and reversible manner. Through a combination of thin-film growth, transmission-electron-microscopy-based nanobeam diffraction and nanoscale band-excitation switching spectroscopy, we show that strain gradients in compositionally graded PbZr 1-xTimore » xO 3 heterostructures stabilize needle-like ferroelastic domains that terminate inside the film. These needle-like domains are highly labile in the out-of-plane direction under applied electric fields, producing a locally enhanced piezoresponse. This work demonstrates the efficacy of novel modes of epitaxy in providing new modalities of domain engineering and potential for as-yet-unrealized nanoscale functional devices.« less

  5. Highly mobile ferroelastic domain walls in compositionally graded ferroelectric thin films

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

    Damodaran, Anoop; Okatan, M. B.; Kacher, J.

    Domains and domain walls are critical in determining the response of ferroelectrics, and the ability to controllably create, annihilate, or move domains is essential to enable a range of next-generation devices. Whereas electric-field control has been demonstrated for ferroelectric 180° domain walls, similar control of ferroelastic domains has not been achieved. Here, using controlled composition and strain gradients, we demonstrate deterministic control of ferroelastic domains that are rendered highly mobile in a controlled and reversible manner. Through a combination of thin-film growth, transmission-electron-microscopy-based nanobeam diffraction and nanoscale band-excitation switching spectroscopy, we show that strain gradients in compositionally graded PbZr 1-xTimore » xO 3 heterostructures stabilize needle-like ferroelastic domains that terminate inside the film. These needle-like domains are highly labile in the out-of-plane direction under applied electric fields, producing a locally enhanced piezoresponse. This work demonstrates the efficacy of novel modes of epitaxy in providing new modalities of domain engineering and potential for as-yet-unrealized nanoscale functional devices.« less

  6. Distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases of Actinobacteria.

    PubMed

    Ogawara, Hiroshi

    2016-09-01

    PASTA domains (penicillin-binding protein and serine/threonine kinase-associated domains) have been identified in penicillin-binding proteins and serine/threonine kinases of Gram-positive Firmicutes and Actinobacteria. They are believed to bind β-lactam antibiotics, and be involved in peptidoglycan metabolism, although their biological function is not definitively clarified. Actinobacteria, especially Streptomyces species, are distinct in that they undergo complex cellular differentiation and produce various antibiotics including β-lactams. This review focuses on the distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases in Actinobacteria. In Actinobacteria, PASTA domains are detectable exclusively in class A but not in class B penicillin-binding proteins, in sharp contrast to the cases in other bacteria. In penicillin-binding proteins, PASTA domains distribute independently from taxonomy with some distribution bias. Particularly interesting thing is that no Streptomyces species have penicillin-binding protein with PASTA domains. Protein kinases in Actinobacteria possess 0 to 5 PASTA domains in their molecules. Protein kinases in Streptomyces can be classified into three groups: no PASTA domain, 1 PASTA domain and 4 PASTA domain-containing groups. The 4 PASTA domain-containing groups can be further divided into two subgroups. The serine/threonine kinases in different groups may perform different functions. The pocket region in one of these subgroup is more dense and extended, thus it may be involved in binding of ligands like β-lactams more efficiently.

  7. Topological-charge-driven reversal of ferromagnetic rings via 360∘ domain-wall formation

    NASA Astrophysics Data System (ADS)

    Oyarce, A. L. Gonzalez; Trypiniotis, T.; Roy, P. E.; Barnes, C. H. W.

    2013-05-01

    We study the reversal mechanism between opposite closed flux states of ferromagnetic nanorings driven by an azimuthal magnetic field. The reversal proceeds via the formation of 360∘ domain walls, and we show that the role of interacting nucleation sites is essential for the process to take place. Such nucleation is seen to create domain walls with the right topological charge conditions for 360∘ domain-wall formation. Given the symmetry of the system, we utilize an energetic description as a function of the azimuthal field magnitude, which clearly reveals the different stages of this reversal process. The annihilation of the 360∘ domain walls that is necessary for the reversal process to complete is controlling the field value at the final stage of the process. Such a fundamental mechanism for ring reversal has several implications and will guide the design of the various data-storage-device proposals based on nanorings.

  8. Binding Rate Constants Reveal Distinct Features of Disordered Protein Domains.

    PubMed

    Dogan, Jakob; Jonasson, Josefin; Andersson, Eva; Jemth, Per

    2015-08-04

    Intrinsically disordered proteins (IDPs) are abundant in the proteome and involved in key cellular functions. However, experimental data about the binding kinetics of IDPs as a function of different environmental conditions are scarce. We have performed an extensive characterization of the ionic strength dependence of the interaction between the molten globular nuclear co-activator binding domain (NCBD) of CREB binding protein and five different protein ligands, including the intrinsically disordered activation domain of p160 transcriptional co-activators (SRC1, TIF2, ACTR), the p53 transactivation domain, and the folded pointed domain (PNT) of transcription factor ETS-2. Direct comparisons of the binding rate constants under identical conditions show that the association rate constant, kon, for interactions between NCBD and disordered protein domains is high at low salt concentrations (90-350 × 10(6) M(-1) s(-1) at 4 °C) but is reduced significantly (10-30-fold) with an increasing ionic strength and reaches a plateau around physiological ionic strength. In contrast, the kon for the interaction between NCBD and the folded PNT domain is only 7 × 10(6) M(-1) s(-1) (4 °C and low salt) and displays weak ionic strength dependence, which could reflect a distinctly different association that relies less on electrostatic interactions. Furthermore, the basal rate constant (in the absence of electrostatic interactions) is high for the NCBD interactions, exceeding those typically observed for folded proteins. One likely interpretation is that disordered proteins have a large number of possible collisions leading to a productive on-pathway encounter complex, while folded proteins are more restricted in terms of orientation. Our results highlight the importance of electrostatic interactions in binding involving IDPs and emphasize the significance of including ionic strength as a factor in studies that compare the binding properties of IDPs to those of ordered proteins.

  9. Primordial black hole and wormhole formation by domain walls

    NASA Astrophysics Data System (ADS)

    Deng, Heling; Garriga, Jaume; Vilenkin, Alexander

    2017-04-01

    In theories with a broken discrete symmetry, Hubble sized spherical domain walls may spontaneously nucleate during inflation. These objects are subsequently stretched by the inflationary expansion, resulting in a broad distribution of sizes. The fate of the walls after inflation depends on their radius. Walls smaller than a critical radius fall within the cosmological horizon early on and collapse due to their own tension, forming ordinary black holes. But if a wall is large enough, its repulsive gravitational field becomes dominant much before the wall can fall within the cosmological horizon. In this ``supercritical'' case, a wormhole throat develops, connecting the ambient exterior FRW universe with an interior baby universe, where the exponential growth of the wall radius takes place. The wormhole pinches off in a time-scale comparable to its light-crossing time, and black holes are formed at its two mouths. As discussed in previous work, the resulting black hole population has a wide distribution of masses and can have significant astrophysical effects. The mechanism of black hole formation has been previously studied for a dust-dominated universe. Here we investigate the case of a radiation-dominated universe, which is more relevant cosmologically, by using numerical simulations in order to find the initial mass of a black hole as a function of the wall size at the end of inflation. For large supercritical domain walls, this mass nearly saturates the upper bound according to which the black hole cannot be larger than the cosmological horizon. We also find that the subsequent accretion of radiation satisfies a scaling relation, resulting in a mass increase by about a factor of 2.

  10. Primordial black hole and wormhole formation by domain walls

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

    Deng, Heling; Garriga, Jaume; Vilenkin, Alexander, E-mail: heling.deng@tufts.edu, E-mail: garriga@cosmos.phy.tufts.edu, E-mail: vilenkin@cosmos.phy.tufts.edu

    In theories with a broken discrete symmetry, Hubble sized spherical domain walls may spontaneously nucleate during inflation. These objects are subsequently stretched by the inflationary expansion, resulting in a broad distribution of sizes. The fate of the walls after inflation depends on their radius. Walls smaller than a critical radius fall within the cosmological horizon early on and collapse due to their own tension, forming ordinary black holes. But if a wall is large enough, its repulsive gravitational field becomes dominant much before the wall can fall within the cosmological horizon. In this ''supercritical'' case, a wormhole throat develops, connectingmore » the ambient exterior FRW universe with an interior baby universe, where the exponential growth of the wall radius takes place. The wormhole pinches off in a time-scale comparable to its light-crossing time, and black holes are formed at its two mouths. As discussed in previous work, the resulting black hole population has a wide distribution of masses and can have significant astrophysical effects. The mechanism of black hole formation has been previously studied for a dust-dominated universe. Here we investigate the case of a radiation-dominated universe, which is more relevant cosmologically, by using numerical simulations in order to find the initial mass of a black hole as a function of the wall size at the end of inflation. For large supercritical domain walls, this mass nearly saturates the upper bound according to which the black hole cannot be larger than the cosmological horizon. We also find that the subsequent accretion of radiation satisfies a scaling relation, resulting in a mass increase by about a factor of 2.« less

  11. Current-induced domain wall motion in permalloy nanowires with a rectangular cross-section

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

    Ai, J. H.; Miao, B. F.; Sun, L.

    2011-11-01

    We performed micromagnetic simulations of the current-induced domain wall motion in permalloy nanowires with rectangular cross-section. In the absence of the nonadiabatic spin-transfer term, a threshold current, J{sub c} is required to drive the domain wall moving continuously. We find that J{sub c} is proportional to the maximum cross product of the demagnetization field and magnetization orientation of the domain wall and the domain wall width. With varying both the wire thickness and width, a minimum threshold current in the order of 10{sup 6} A/cm{sup 2} is obtained when the thickness is equivalent to the wire width. With the nonadiabaticmore » spin-transfer term, the calculated domain wall velocity {nu} equals to the adiabatic spin transfer velocity u when the current is far above the Walker limit J{sub w}. Below J{sub w}, {nu}=({beta}/{alpha})u, where {beta} is the nonadiabatic parameter and {alpha} is the damping factor. For different {beta}, we find the Walker limit can be scaled as J{sub w}=({alpha}/{beta}-{alpha})J{sub c}. Our simulations agree well with the one dimensional analytical calculation, suggesting the findings are the general behaviors of the systems in this particular geometry.« less

  12. Binding preference of carbon nanotube over proline-rich motif ligand on SH3-domain: a comparison with different force fields.

    PubMed

    Shi, Biyun; Zuo, Guanghong; Xiu, Peng; Zhou, Ruhong

    2013-04-04

    With the widespread applications of nanomaterials such as carbon nanotubes, there is a growing concern on the biosafety of these engineered nanoparticles, in particular their interactions with proteins. In molecular simulations of nanoparticle-protein interactions, the choice of empirical parameters (force fields) plays a decisive role, and thus is of great importance and should be examined carefully before wider applications. Here we compare three commonly used force fields, CHARMM, OPLSAA, and AMBER in study of the competitive binding of a single wall carbon nanotube (SWCNT) with a native proline-rich motif (PRM) ligand on its target protein SH3 domain, a ubiquitous protein-protein interaction mediator involved in signaling and regulatory pathways. We find that the SWCNT displays a general preference over the PRM in binding with SH3 domain in all the three force fields examined, although the degree of preference can be somewhat different, with the AMBER force field showing the highest preference. The SWCNT prevents the ligand from reaching its native binding pocket by (i) occupying the binding pocket directly, and (ii) binding with the ligand itself and then being trapped together onto some off-sites. The π-π stacking interactions between the SWCNT and aromatic residues are found to play a significant role in its binding to the SH3 domain in all the three force fields. Further analyses show that even the SWCNT-ligand binding can also be relatively more stable than the native ligand-protein binding, indicating a serious potential disruption to the protein SH3 function.

  13. Cellulose binding domain fusion proteins

    DOEpatents

    Shoseyov, O.; Yosef, K.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1998-02-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  14. Cellulose binding domain fusion proteins

    DOEpatents

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  15. Out-of-plane chiral domain wall spin-structures in ultrathin in-plane magnets

    DOE PAGES

    Chen, Gong; Kang, Sang Pyo; Ophus, Colin; ...

    2017-05-19

    Chiral spin textures in ultrathin films, such as skyrmions or chiral domain walls, are believed to offer large performance advantages in the development of novel spintronics technologies. While in-plane magnetized films have been studied extensively as media for current- and field-driven domain wall dynamics with applications in memory or logic devices, the stabilization of chiral spin textures in in-plane magnetized films has remained rare. Here we report a phase of spin structures in an in-plane magnetized ultrathin film system where out-of-plane spin orientations within domain walls are stable. Moreover, while domain walls in in-plane films are generally expected to bemore » non-chiral, we show that right-handed spin rotations are strongly favoured in this system, due to the presence of the interfacial Dzyaloshinskii-Moriya interaction. These results constitute a platform to explore unconventional spin dynamics and topological phenomena that may enable high-performance in-plane spin-orbitronics devices.« less

  16. Tachyon condensation due to domain-wall annihilation in Bose-Einstein condensates.

    PubMed

    Takeuchi, Hiromitsu; Kasamatsu, Kenichi; Tsubota, Makoto; Nitta, Muneto

    2012-12-14

    We show theoretically that a domain-wall annihilation in two-component Bose-Einstein condensates causes tachyon condensation accompanied by spontaneous symmetry breaking in a two-dimensional subspace. Three-dimensional vortex formation from domain-wall annihilations is considered a kink formation in subspace. Numerical experiments reveal that the subspatial dynamics obey the dynamic scaling law of phase-ordering kinetics. This model is experimentally feasible and provides insights into how the extra dimensions influence subspatial phase transition in higher-dimensional space.

  17. Excess velocity of magnetic domain walls close to the depinning field

    NASA Astrophysics Data System (ADS)

    Caballero, Nirvana B.; Fernández Aguirre, Iván; Albornoz, Lucas J.; Kolton, Alejandro B.; Rojas-Sánchez, Juan Carlos; Collin, Sophie; George, Jean Marie; Diaz Pardo, Rebeca; Jeudy, Vincent; Bustingorry, Sebastian; Curiale, Javier

    2017-12-01

    Magnetic field driven domain wall velocities in [Co/Ni] based multilayers thin films have been measured using polar magneto-optic Kerr effect microscopy. The low field results are shown to be consistent with the universal creep regime of domain wall motion, characterized by a stretched exponential growth of the velocity with the inverse of the applied field. Approaching the depinning field from below results in an unexpected excess velocity with respect to the creep law. We analyze these results using scaling theory to show that this speeding up of domain wall motion can be interpreted as due to the increase of the size of the deterministic relaxation close to the depinning transition. We propose a phenomenological model to accurately fit the observed excess velocity and to obtain characteristic values for the depinning field Hd, the depinning temperature Td, and the characteristic velocity scale v0 for each sample.

  18. Flexible DNA binding of the BTB/POZ-domain protein FBI-1.

    PubMed

    Pessler, Frank; Hernandez, Nouria

    2003-08-01

    POZ-domain transcription factors are characterized by the presence of a protein-protein interaction domain called the POZ or BTB domain at their N terminus and zinc fingers at their C terminus. Despite the large number of POZ-domain transcription factors that have been identified to date and the significant insights that have been gained into their cellular functions, relatively little is known about their DNA binding properties. FBI-1 is a BTB/POZ-domain protein that has been shown to modulate HIV-1 Tat trans-activation and to repress transcription of some cellular genes. We have used various viral and cellular FBI-1 binding sites to characterize the interaction of a POZ-domain protein with DNA in detail. We find that FBI-1 binds to inverted sequence repeats downstream of the HIV-1 transcription start site. Remarkably, it binds efficiently to probes carrying these repeats in various orientations and spacings with no particular rotational alignment, indicating that its interaction with DNA is highly flexible. Indeed, FBI-1 binding sites in the adenovirus 2 major late promoter, the c-fos gene, and the c-myc P1 and P2 promoters reveal variously spaced direct, inverted, and everted sequence repeats with the consensus sequence G(A/G)GGG(T/C)(C/T)(T/C)(C/T) for each repeat.

  19. Cosmic bubble and domain wall instabilities II: fracturing of colliding walls

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

    Braden, Jonathan; Bond, J. Richard; Mersini-Houghton, Laura, E-mail: j.braden@ucl.ac.uk, E-mail: bond@cita.utoronto.ca, E-mail: mersini@physics.unc.edu

    2015-08-01

    We study collisions between nearly planar domain walls including the effects of small initial nonplanar fluctuations. These perturbations represent the small fluctuations that must exist in a quantum treatment of the problem. In a previous paper, we demonstrated that at the linear level a subset of these fluctuations experience parametric amplification as a result of their coupling to the planar symmetric background. Here we study the full three-dimensional nonlinear dynamics using lattice simulations, including both the early time regime when the fluctuations are well described by linear perturbation theory as well as the subsequent stage of fully nonlinear evolution. Wemore » find that the nonplanar fluctuations have a dramatic effect on the overall evolution of the system. Specifically, once these fluctuations begin to interact nonlinearly the split into a planar symmetric part of the field and the nonplanar fluctuations loses its utility. At this point the colliding domain walls dissolve, with the endpoint of this being the creation of a population of oscillons in the collision region. The original (nearly) planar symmetry has been completely destroyed at this point and an accurate study of the system requires the full three-dimensional simulation.« less

  20. Cosmic bubble and domain wall instabilities II: fracturing of colliding walls

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

    Braden, Jonathan; Department of Physics, University of Toronto,60 St. George Street, Toronto, ON, M5S 3H8; Department of Physics and Astronomy, University College London,Gower Street, London, WC1E 6BT

    2015-08-26

    We study collisions between nearly planar domain walls including the effects of small initial nonplanar fluctuations. These perturbations represent the small fluctuations that must exist in a quantum treatment of the problem. In a previous paper, we demonstrated that at the linear level a subset of these fluctuations experience parametric amplification as a result of their coupling to the planar symmetric background. Here we study the full three-dimensional nonlinear dynamics using lattice simulations, including both the early time regime when the fluctuations are well described by linear perturbation theory as well as the subsequent stage of fully nonlinear evolution. Wemore » find that the nonplanar fluctuations have a dramatic effect on the overall evolution of the system. Specifically, once these fluctuations begin to interact nonlinearly the split into a planar symmetric part of the field and the nonplanar fluctuations loses its utility. At this point the colliding domain walls dissolve, with the endpoint of this being the creation of a population of oscillons in the collision region. The original (nearly) planar symmetry has been completely destroyed at this point and an accurate study of the system requires the full three-dimensional simulation.« less

  1. IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold*

    PubMed Central

    Dixon, Miles J.; Gray, Alexander; Schenning, Martijn; Agacan, Mark; Tempel, Wolfram; Tong, Yufeng; Nedyalkova, Lyudmila; Park, Hee-Won; Leslie, Nicholas R.; van Aalten, Daan M. F.; Downes, C. Peter; Batty, Ian H.

    2012-01-01

    Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105–107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those of the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules. PMID:22493426

  2. IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold

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

    Dixon, Miles J.; Gray, Alexander; Schenning, Martijn

    2012-10-16

    Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those ofmore » the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.« less

  3. Evolution of light domain walls interacting with dark matter, part 1

    NASA Technical Reports Server (NTRS)

    Massarotti, Alessandro

    1990-01-01

    The evolution of domain walls generated in the early Universe is discussed considering an interaction between the walls and a major gaseous component of the dark matter. The walls are supposed able to reflect the particles elastically and with a reflection coefficient of unity. A toy Lagrangian that could give rise to such a phenomenon is discussed. In the simple model studied, highly non-relativistic and slowly varying speeds are obtained for the domain walls (approximately 10 (exp -2)(1+z)(exp -1)) and negligible distortions of the microwave background. In addition, these topological defects may provide a mechanism of forming the large scale structure of the Universe, by creating fluctuations in the dark matter (delta rho/rho approximately O(1)) on a scale comparable with the distance the walls move from the formation (in the model d less than 20 h(exp -1) Mpc). The characteristic scale of the wall separation can be easily chosen to be of the order of 100 Mpc instead of being restricted to the horizon scale, as usually obtained.

  4. Domain wall energy landscapes in amorphous magnetic films with asymmetric arrays of holes

    NASA Astrophysics Data System (ADS)

    Alija, A.; Pérez-Junquera, A.; Rodríguez-Rodríguez, G.; Vélez, M.; Marconi, V. I.; Kolton, A. B.; Anguita, J. V.; Alameda, J. M.; Parrondo, J. M. R.; Martín, J. I.

    2009-02-01

    Arrays of asymmetric holes have been defined in amorphous Co-Si films by e-beam lithography in order to study domain wall motion across the array subject to the asymmetric pinning potential created by the holes. Experimental results on Kerr effect magnetooptical measurements and hysteresis loops are compared with micromagnetic simulations in films with arrays of triangular holes. These show that the potential asymmetry favours forward wall propagation for flat walls but, if the wall contains a kink, net backward wall propagation is preferred at low fields, in agreement with minor loop experiments. The difference between the fields needed for forward and backward flat wall propagation increases as the size of the triangular holes is reduced, becoming maximum for 1 µm triangles, which is the characteristic length scale set by domain wall width.

  5. Remarkably enhanced current-driven 360° domain wall motion in nanostripe by tuning in-plane biaxial anisotropy.

    PubMed

    Su, Yuanchang; Weng, Lianghao; Dong, Wenjun; Xi, Bin; Xiong, Rui; Hu, Jingguo

    2017-10-17

    By micromagnetic simulations, we study the current-driven 360° domain wall (360DW) motion in ferromagnetic nanostripe with an in-plane biaxial anisotropy. We observe the critical annihilation current of 360° domain wall can be enhanced through such a type of anisotropy, the reason of which is the suppression of out-of-plane magnetic moments generated simultaneously with domain-wall motion. In details, We have found that the domain-wall width is only related to K y  - K x , with K x(y) the anisotropy constant in x(y) direction. Taking domain-wall width into consideration, a prior choice is to keep K y  ≈ K x with large enough K. The mode of domain-wall motion has been investigated as well. The traveling-wave-motion region increases with K, while the average DW velocity is almost unchanged. Another noteworthy feature is that a Walker-breakdown-like motion exists before annihilation. In this region, though domain wall moves with an oscillating behavior, the average velocity does not reduce dramatically, but even rise again for a large K.

  6. Biosensors engineered from conditionally stable ligand-binding domains

    DOEpatents

    Church, George M.; Feng, Justin; Mandell, Daniel J.; Baker, David; Fields, Stanley; Jester, Benjamin Ward; Tinberg, Christine Elaine

    2017-09-19

    Disclosed is a biosensor engineered to conditionally respond to the presence of specific small molecules, the biosensors including conditionally stable ligand-binding domains (LBDs) which respond to the presence of specific small molecules, wherein readout of binding is provided by reporter genes or transcription factors (TFs) fused to the LBDs.

  7. Domain wall dynamics driven by spin transfer torque and the spin-orbit field.

    PubMed

    Hayashi, Masamitsu; Nakatani, Yoshinobu; Fukami, Shunsuke; Yamanouchi, Michihiko; Mitani, Seiji; Ohno, Hideo

    2012-01-18

    We have studied current-driven dynamics of domain walls when an in-plane magnetic field is present in perpendicularly magnetized nanowires using an analytical model and micromagnetic simulations. We model an experimentally studied system, ultrathin magnetic nanowires with perpendicular anisotropy, where an effective in-plane magnetic field is developed when current is passed along the nanowire due to the Rashba-like spin-orbit coupling. Using a one-dimensional model of a domain wall together with micromagnetic simulations, we show that the existence of such in-plane magnetic fields can either lower or raise the threshold current needed to cause domain wall motion. In the presence of the in-plane field, the threshold current differs for positive and negative currents for a given wall chirality, and the wall motion becomes sensitive to out-of-plane magnetic fields. We show that large non-adiabatic spin torque can counteract the effect of the in-plane field.

  8. Electrical conduction at domain walls in multiferroic BiFeO3

    NASA Astrophysics Data System (ADS)

    Seidel, Jan; Martin, Lane; He, Qing; Zhan, Qian; Chu, Ying-Hao; Rother, Axel; Hawkridge, Michael; Maksymovych, Peter; Yu, Pu; Gajek, Martin; Balke, Nina; Kalinin, Sergei; Gemming, Sybille; Wang, Feng; Catalán, Gustau; Scott, James; Spaldin, Nicola; Orenstein, Joseph; Ramesh, Ramamoorthy

    2009-03-01

    We report the observation of room temperature electronic conductivity at ferroelectric domain walls in BiFeO3. The origin and nature of the observed conductivity is probed using a combination of conductive atomic force microscopy, high resolution transmission electron microscopy and first-principles density functional computations. We show that a structurally driven change in both the electrostatic potential and local electronic structure (i.e., a decrease in band gap) at the domain wall leads to the observed electrical conductivity. We estimate the conductivity in the wall to be several orders of magnitude higher than for the bulk material. Additionally we demonstrate the potential for device applications of such conducting nanoscale features.

  9. A low-complexity region in the YTH domain protein Mmi1 enhances RNA binding.

    PubMed

    Stowell, James A W; Wagstaff, Jane L; Hill, Chris H; Yu, Minmin; McLaughlin, Stephen H; Freund, Stefan M V; Passmore, Lori A

    2018-06-15

    Mmi1 is an essential RNA-binding protein in the fission yeast Schizosaccharomyces pombe that eliminates meiotic transcripts during normal vegetative growth. Mmi1 contains a YTH domain that binds specific RNA sequences, targeting mRNAs for degradation. The YTH domain of Mmi1 uses a noncanonical RNA-binding surface that includes contacts outside the conserved fold. Here, we report that an N-terminal extension that is proximal to the YTH domain enhances RNA binding. Using X-ray crystallography, NMR, and biophysical methods, we show that this low-complexity region becomes more ordered upon RNA binding. This enhances the affinity of the interaction of the Mmi1 YTH domain with specific RNAs by reducing the dissociation rate of the Mmi1-RNA complex. We propose that the low-complexity region influences RNA binding indirectly by reducing dynamic motions of the RNA-binding groove and stabilizing a conformation of the YTH domain that binds to RNA with high affinity. Taken together, our work reveals how a low-complexity region proximal to a conserved folded domain can adopt an ordered structure to aid nucleic acid binding. © 2018 Stowell et al.

  10. Comparison of S. cerevisiae F-BAR domain structures reveals a conserved inositol phosphate binding site

    PubMed Central

    Moravcevic, Katarina; Alvarado, Diego; Schmitz, Karl R.; Kenniston, Jon A.; Mendrola, Jeannine M.; Ferguson, Kathryn M.; Lemmon, Mark A.

    2015-01-01

    SUMMARY F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here, we compare membrane-binding properties of the S. cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences, and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip, and is partly retained in certain other F-BAR domains. Our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity, and provide a basis for its prediction from sequence. PMID:25620000

  11. Exact BPS domain walls at finite gauge coupling

    NASA Astrophysics Data System (ADS)

    Blaschke, Filip

    2017-01-01

    Bogomol'nyi-Prasad-Sommerfield solitons in models with spontaneously broken gauge symmetry have been intensively studied at the infinite gauge coupling limit, where the governing equation-the so-called master equation-is exactly solvable. Except for a handful of special solutions, the standing impression is that analytic results at finite coupling are generally unavailable. The aim of this paper is to demonstrate, using domain walls in Abelian-Higgs models as the simplest example, that exact solitons at finite gauge coupling can be readily obtained if the number of Higgs fields (NF ) is large enough. In particular, we present a family of exact solutions, describing N domain walls at arbitrary positions in models with at least NF≥2 N +1 . We have also found that adding together any pair of solutions can produce a new exact solution if the combined tension is below a certain limit.

  12. Stereochemical determinants of C-terminal specificity in PDZ peptide-binding domains: a novel contribution of the carboxylate-binding loop.

    PubMed

    Amacher, Jeanine F; Cushing, Patrick R; Bahl, Christopher D; Beck, Tobias; Madden, Dean R

    2013-02-15

    PDZ (PSD-95/Dlg/ZO-1) binding domains often serve as cellular traffic engineers, controlling the localization and activity of a wide variety of binding partners. As a result, they play important roles in both physiological and pathological processes. However, PDZ binding specificities overlap, allowing multiple PDZ proteins to mediate distinct effects on shared binding partners. For example, several PDZ domains bind the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), an epithelial ion channel mutated in CF. Among these binding partners, the CFTR-associated ligand (CAL) facilitates post-maturational degradation of the channel and is thus a potential therapeutic target. Using iterative optimization, we previously developed a selective CAL inhibitor peptide (iCAL36). Here, we investigate the stereochemical basis of iCAL36 specificity. The crystal structure of iCAL36 in complex with the CAL PDZ domain reveals stereochemical interactions distributed along the peptide-binding cleft, despite the apparent degeneracy of the CAL binding motif. A critical selectivity determinant that distinguishes CAL from other CFTR-binding PDZ domains is the accommodation of an isoleucine residue at the C-terminal position (P(0)), a characteristic shared with the Tax-interacting protein-1. Comparison of the structures of these two PDZ domains in complex with ligands containing P(0) Leu or Ile residues reveals two distinct modes of accommodation for β-branched C-terminal side chains. Access to each mode is controlled by distinct residues in the carboxylate-binding loop. These studies provide new insights into the primary sequence determinants of binding motifs, which in turn control the scope and evolution of PDZ interactomes.

  13. Structural and functional analysis of the YAP-binding domain of human TEAD2

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

    Tian, Wei; Yu, Jianzhong; Tomchick, Diana R.

    2010-06-15

    The Hippo pathway controls organ size and suppresses tumorigenesis in metazoans by blocking cell proliferation and promoting apoptosis. The TEAD1-4 proteins (which contain a DNA-binding domain but lack an activation domain) interact with YAP (which lacks a DNA-binding domain but contains an activation domain) to form functional heterodimeric transcription factors that activate proliferative and prosurvival gene expression programs. The Hippo pathway inhibits the YAP-TEAD hybrid transcription factors by phosphorylating and promoting cytoplasmic retention of YAP. Here we report the crystal structure of the YAP-binding domain (YBD) of human TEAD2. TEAD2 YBD adopts an immunoglobulin-like {beta}-sandwich fold with two extra helix-turn-helixmore » inserts. NMR studies reveal that the TEAD-binding domain of YAP is natively unfolded and that TEAD binding causes localized conformational changes in YAP. In vitro binding and in vivo functional assays define an extensive conserved surface of TEAD2 YBD as the YAP-binding site. Therefore, our studies suggest that a short segment of YAP adopts an extended conformation and forms extensive contacts with a rigid surface of TEAD. Targeting a surface-exposed pocket of TEAD might be an effective strategy to disrupt the YAP-TEAD interaction and to reduce the oncogenic potential of YAP.« less

  14. Reflection of antiferromagnetic vortices on a supersonic domain wall in yttrium orthoferrite

    NASA Astrophysics Data System (ADS)

    Chetkin, M. V.; Kurbatova, Yu. N.; Shapaeva, T. B.; Borschegovsky, O. A.

    2007-04-01

    Reflection of solitary flexural waves propagating in a supersonic domain wall of yttrium orthoferrite from the domain wall part moving with the transverse-sound velocity is observed experimentally. This observation confirms that such a reflection of a solitary flexural wave leads to a change in the sign of the topological charge of the antiferromagnetic vortex accompanied by this wave, which proves a direct relationship between these two objects.

  15. Influence of Joule heating on current-induced domain wall depinning

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

    Moretti, Simone, E-mail: simone.moretti@usal.es; Raposo, Victor; Martinez, Eduardo

    2016-06-07

    The domain wall depinning from a notch in a Permalloy nanostrip on top of a SiO{sub 2}/Si substrate is studied theoretically under application of static magnetic fields and the injection of short current pulses. The influence of Joule heating on current-induced domain wall depinning is explored self-consistently by coupling the magnetization dynamics in the ferromagnetic strip to the heat transport throughout the system. Our results indicate that Joule heating plays a remarkable role in these processes, resulting in a reduction in the critical depinning field and/or in a temporary destruction of the ferromagnetic order for typically injected current pulses. Inmore » agreement with experimental observations, similar pinning-depinning phase diagrams can be deduced for both current polarities when the Joule heating is taken into account. These observations, which are incompatible with the sole contribution of spin transfer torques, provide a deeper understanding of the physics underlying these processes and establish the real scope of the spin transfer torque. They are also relevant for technological applications based on current-induced domain-wall motion along soft strips.« less

  16. Distinct Ubiquitin Binding Modes Exhibited by SH3 Domains: Molecular Determinants and Functional Implications

    PubMed Central

    Ortega Roldan, Jose L.; Casares, Salvador; Ringkjøbing Jensen, Malene; Cárdenes, Nayra; Bravo, Jerónimo; Blackledge, Martin; Azuaga, Ana I.; van Nuland, Nico A. J.

    2013-01-01

    SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C) of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination. PMID:24039852

  17. Simultaneous Binding of Two Peptidyl Ligands by a Src Homology 2 Domain

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

    Zhang, Yanyan; Zhang, Jinjin; Yuan, Chunhua

    Src homology 2 (SH2) domains mediate protein-protein interactions by recognizing phosphotyrosine (pY)-containing sequences of target proteins. In all of the SH2 domain-pY peptide interactions described to date, the SH2 domain binds to a single pY peptide. Here, determination of the cocrystal structure of the N-terminal SH2 domain of phosphatase SHP-2 bound to a class IV peptide (VIpYFVP) revealed a noncanonical 1:2 (protein-peptide) complex. The first peptide binds in a canonical manner with its pY side chain inserted in the usual binding pocket, while the second pairs up with the first to form two antiparallel {beta}-strands that extend the central {beta}-sheetmore » of the SH2 domain. This unprecedented binding mode was confirmed in the solution phase by NMR experiments and shown to be adopted by pY peptides derived from cellular proteins. Site-directed mutagenesis and surface plasmon resonance studies revealed that the binding of the first peptide is pY-dependent, but phosphorylation is not required for the second peptide. Our findings suggest a potential new function for the SH2 domain as a molecular clamp to promote dimerization of signaling proteins.« less

  18. Atypical binding of the Swa2p UBA domain to ubiquitin.

    PubMed

    Matta-Camacho, Edna; Kozlov, Guennadi; Trempe, Jean-François; Gehring, Kalle

    2009-02-20

    Swa2p is an auxilin-like yeast protein that is involved in vesicular transport and required for uncoating of clathrin-coated vesicles. Swa2p contains a ubiquitin-associated (UBA) domain, which is present in a variety of proteins involved in ubiquitin (Ub)-mediated processes. We have determined a structural model of the Swa2p UBA domain in complex with Ub using NMR spectroscopy and molecular docking. Ub recognition occurs predominantly through an atypical interaction in which UBA helix alpha1 and the N-terminal part of helix alpha2 bind to Ub. Mutation of Ala148, a key residue in helix alpha1, to polar residues greatly reduced the affinity of the UBA domain for Ub and revealed a second low-affinity Ub-binding site located on the surface formed by helices alpha1 and alpha3. Surface plasmon resonance showed that the Swa2p UBA domain binds K48- and K63-linked di-Ub in a non-linkage-specific manner. These results reveal convergent evolution of a Ub-binding site on helix alpha1 of UBA domains involved in membrane protein trafficking.

  19. Comparison of Saccharomyces cerevisiae F-BAR domain structures reveals a conserved inositol phosphate binding site.

    PubMed

    Moravcevic, Katarina; Alvarado, Diego; Schmitz, Karl R; Kenniston, Jon A; Mendrola, Jeannine M; Ferguson, Kathryn M; Lemmon, Mark A

    2015-02-03

    F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although they are generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here, we compare membrane-binding properties of the Saccharomyces cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip and is partly retained in certain other F-BAR domains. Our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity and provide a basis for its prediction from sequence. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Comparison of Saccharomyces cerevisiae F-BAR Domain Structures Reveals a Conserved Inositol Phosphate Binding Site

    DOE PAGES

    Moravcevic, Katarina; Alvarado, Diego; Schmitz, Karl R.; ...

    2015-01-22

    F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although they are generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here in this paper, we compare membrane-binding properties of the Saccharomyces cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound tomore » an inositol phosphate. The structures explain phospholipid-binding selectivity differences and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip and is partly retained in certain other F-BAR domains. In conclusion, our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity and provide a basis for its prediction from sequence.« less

  1. Crystallization and preliminary crystallographic analysis of the transpeptidase domain of penicillin-binding protein 2B from Streptococcus pneumoniae

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

    Yamada, Mototsugu, E-mail: mototsugu-yamada@meiji.co.jp; Watanabe, Takashi; Baba, Nobuyoshi

    The selenomethionyl-substituted transpeptidase domain of penicillin-binding protein (PBP) 2B from S. pneumoniae was isolated from a limited proteolysis digest of the soluble form of recombinant PBP 2B and then crystallized. MAD data were collected to 2.4 Å resolution. Penicillin-binding protein (PBP) 2B from Streptococcus pneumoniae catalyzes the cross-linking of peptidoglycan precursors that occurs during bacterial cell-wall biosynthesis. A selenomethionyl (SeMet) substituted PBP 2B transpeptidase domain was isolated from a limited proteolysis digest of a soluble form of recombinant PBP 2B and then crystallized. The crystals belonged to space group P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 86.39,more » c = 143.27 Å. Diffraction data were collected to 2.4 Å resolution using the BL32B2 beamline at SPring-8. The asymmetric unit contains one protein molecule and 63.7% solvent.« less

  2. The dynamics of domain walls and strings

    NASA Technical Reports Server (NTRS)

    Gregory, Ruth; Haws, David; Garfinkle, David

    1989-01-01

    The leading order finite-width corrections to the equation of motion describing the motion of a domain wall are derived. The regime in which this equation of motion is invalid is discussed. Spherically and cylindrically symmetric solutions to this equation of motion are found. A misconception that has arisen in recent years regarding the rigidity (or otherwise) of cosmic strings is also clarified.

  3. Trajectory and chirality of vortex domain walls in ferromagnetic nanowires with an asymmetric Y-branch

    NASA Astrophysics Data System (ADS)

    Brandão, J.; Mello, A.; Garcia, F.; Sampaio, L. C.

    2017-03-01

    The motion and trajectory of vortex domain walls (VDWs) driven by magnetic field were investigated in Fe80Ni20 nanowires with an asymmetric Y-shape branch. By using the focused magneto-optical Kerr effect, we have probed the injection, pinning, and propagation of VDWs in the branch and in the wire beyond the branch entrance. Hysteresis cycles measured at these points show 3 and 4 jumps in the magnetization reversal, respectively. Micromagnetic simulations were carried out to obtain the number of jumps in the hysteresis cycles, and the magnetization process involved in each jump. Based on simulations and from the size of the jumps in the measured hysteresis cycles, one obtains the histogram of the domain wall type probability. While in the branch domain walls of different types are equiprobable, in the nanowire vortex domain walls with counter clockwise and clockwise chiralities and transverse-down domain walls are measured with probabilities of 65%, 25%, and 10%, respectively. These results provide an additional route to select the trajectory and chirality of VDWs in magnetic nanostructures.

  4. Characterization of αX I-Domain Binding to Receptors for Advanced Glycation End Products (RAGE).

    PubMed

    Buyannemekh, Dolgorsuren; Nham, Sang-Uk

    2017-05-31

    The β2 integrins are cell surface transmembrane proteins regulating leukocyte functions, such as adhesion and migration. Two members of β2 integrin, αMβ2 and αXβ2, share the leukocyte distribution profile and integrin αXβ2 is involved in antigen presentation in dendritic cells and transendothelial migration of monocytes and macrophages to atherosclerotic lesions. Receptor for advanced glycation end products (RAGE), a member of cell adhesion molecules, plays an important role in chronic inflammation and atherosclerosis. Although RAGE and αXβ2 play an important role in inflammatory response and the pathogenesis of atherosclerosis, the nature of their interaction and structure involved in the binding remain poorly defined. In this study, using I-domain as a ligand binding motif of αXβ2, we characterize the binding nature and the interacting moieties of αX I-domain and RAGE. Their binding requires divalent cations (Mg 2+ and Mn 2+ ) and shows an affinity on the sub-micro molar level: the dissociation constant of αX I-domains binding to RAGE being 0.49 μM. Furthermore, the αX I-domains recognize the V-domain, but not the C1 and C2-domains of RAGE. The acidic amino acid substitutions on the ligand binding site of αX I-domain significantly reduce the I-domain binding activity to soluble RAGE and the alanine substitutions of basic amino acids on the flat surface of the V-domain prevent the V-domain binding to αX I-domain. In conclusion, the main mechanism of αX I-domain binding to RAGE is a charge interaction, in which the acidic moieties of αX I-domains, including E244, and D249, recognize the basic residues on the RAGE V-domain encompassing K39, K43, K44, R104, and K107.

  5. Notch-Boosted Domain Wall Propagation in Magnetic Nanowires

    NASA Astrophysics Data System (ADS)

    Wang, Xiang Rong; Yuan, Hauiyang

    Magnetic domain wall (DW) motion along a nanowire underpins many proposals of spintronic devices. High DW propagation velocity is obviously important because it determines the device speed. Thus it is interesting to search for effective control knobs of DW dynamics. We report a counter-intuitive finding that notches in an otherwise homogeneous magnetic nanowire can boost current-induced domain wall (DW) propagation. DW motion in notch-modulated wires can be classified into three phases: 1) A DW is pinned around a notch when the current density is below the depinning current density. 2) DW propagation velocity above the depinning current density is boosted by notches when non-adiabatic spin-transfer torque strength is smaller than the Gilbert damping constant. The boost can be many-fold. 3) DW propagation velocity is hindered when non-adiabatic spin-transfer torque strength is larger than the Gilbert damping constant. This work was supported by Hong Kong GRF Grants (Nos. 163011151 and 605413) and the Grant from NNSF of China (No. 11374249).

  6. The Receptor Binding Domain of Botulinum Neurotoxin Stereotype C Binds Phosphoinositides

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

    Zhang, Yanfeng; Varnum, Susan M.

    2012-03-01

    Botulinum neurotoxins (BoNTs) are the most toxic proteins known for humans and animals with an extremely low LD50 of {approx} 1 ng/kg. BoNTs generally require a protein and a ganglioside on the cell membrane surface for binding, which is known as a 'dual receptor' mechanism for host intoxication. Recent studies have suggested that in addition to gangliosides, other membrane lipids such as phosphoinositides may be involved in the interactions with the receptor binding domain (HCR) of BoNTs for better membrane penetration. Here, using two independent lipid-binding assays, we tested the interactions of BoNT/C-HCR with lipids in vitro. BoNT/C-HCR was foundmore » to bind negatively charged phospholipids, preferentially phosphoinositides. Additional interactions to phosphoinositides may help BoNT/C bind membrane more tightly and transduct signals for subsequent steps of intoxication. Our results provide new insights into the mechanisms of host cell membrane recognition by BoNTs.« less

  7. Interaction between the PH and START domains of ceramide transfer protein competes with phosphatidylinositol 4-phosphate binding by the PH domain

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

    Prashek, Jennifer; Bouyain, Samuel; Fu, Mingui

    De novo synthesis of the sphingolipid sphingomyelin requires non-vesicular transport of ceramide from the endoplasmic reticulum to the Golgi by the multidomain protein ceramide transfer protein (CERT). CERT's N-terminal pleckstrin homology (PH) domain targets it to the Golgi by binding to phosphatidylinositol 4-phosphate (PtdIns(4)P) in the Golgi membrane, whereas its C-terminal StAR-related lipid transfer domain (START) carries out ceramide transfer. Hyperphosphorylation of a serine-rich motif immediately after the PH domain decreases both PtdIns(4)P binding and ceramide transfer by CERT. This down-regulation requires both the PH and START domains, suggesting a possible inhibitory interaction between the two domains. In this studymore » we show that isolated PH and START domains interact with each other. The crystal structure of a PH–START complex revealed that the START domain binds to the PH domain at the same site for PtdIns(4)P-binding, suggesting that the START domain competes with PtdIns(4)P for association with the PH domain. We further report that mutations disrupting the PH–START interaction increase both PtdIns(4)P-binding affinity and ceramide transfer activity of a CERT-serine–rich phosphorylation mimic. We also found that these mutations increase the Golgi localization of CERT inside the cell, consistent with enhanced PtdIns(4)P binding of the mutant. Collectively, our structural, biochemical, and cellular investigations provide important structural insight into the regulation of CERT function and localization.« less

  8. Controlled motion of domain walls in submicron amorphous wires

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

    Ţibu, Mihai; Lostun, Mihaela; Rotărescu, Cristian

    Results on the control of the domain wall displacement in cylindrical Fe{sub 77.5}Si{sub 7.5}B{sub 15} amorphous glass-coated submicron wires prepared by rapid quenching from the melt are reported. The control methods have relied on conical notches with various depths, up to a few tens of nm, made in the glass coating and in the metallic nucleus using a focused ion beam (FIB) system, and on the use of small nucleation coils at one of the sample ends in order to apply magnetic field pulses aimed to enhance the nucleation of reverse domains. The notch-based method is used for the firstmore » time in the case of cylindrical ultrathin wires. The results show that the most efficient technique of controlling the domain wall motion in this type of samples is the simultaneous use of notches and nucleation coils. Their effect depends on wire diameter, notch depth, its position on the wire length, and characteristics of the applied pulse.« less

  9. Effect of spin transfer torque on domain wall motion regimes in [Co/Ni] superlattice wires

    NASA Astrophysics Data System (ADS)

    Le Gall, S.; Vernier, N.; Montaigne, F.; Thiaville, A.; Sampaio, J.; Ravelosona, D.; Mangin, S.; Andrieu, S.; Hauet, T.

    2017-05-01

    The combined effect of magnetic field and current on domain wall motion is investigated in epitaxial [Co/Ni] microwires. Both thermally activated and flow regimes are found to be strongly affected by current. All experimental data can be understood by taking into account both adiabatic and nonadiabatic components of the spin transfer torque, the parameters of which are extracted. In the precessional flow regime, it is shown that the domain wall can move in the electron flow direction against a strong applied field, as previously observed. In addition, for a large range of applied magnetic field and injected current, a stochastic domain wall displacement after each pulse is observed. Two-dimensional micromagnetic simulations, including some disorder, show a random fluctuation of the domain wall position that qualitatively matches the experimental results.

  10. Novel Chiral Magnetic Domain Wall Structure in Fe/Ni/Cu(001) Films

    NASA Astrophysics Data System (ADS)

    Chen, G.; Zhu, J.; Quesada, A.; Li, J.; N'Diaye, A. T.; Huo, Y.; Ma, T. P.; Chen, Y.; Kwon, H. Y.; Won, C.; Qiu, Z. Q.; Schmid, A. K.; Wu, Y. Z.

    2013-04-01

    Using spin-polarized low energy electron microscopy, we discovered a new type of domain wall structure in perpendicularly magnetized Fe/Ni bilayers grown epitaxially on Cu(100). Specifically, we observed unexpected Néel-type walls with fixed chirality in the magnetic stripe phase. Furthermore, we find that the chirality of the domain walls is determined by the film growth order with the chirality being right handed in Fe/Ni bilayers and left handed in Ni/Fe bilayers, suggesting that the underlying mechanism is the Dzyaloshinskii-Moriya interaction at the film interfaces. Our observations may open a new route to control chiral spin structures using interfacial engineering in transition metal heterostructures.

  11. Domain wall dynamics along curved strips under current pulses: The influence of Joule heating

    NASA Astrophysics Data System (ADS)

    Raposo, Victor; Moretti, Simone; Hernandez, Maria Auxiliadora; Martinez, Eduardo

    2016-01-01

    The current-induced domain wall dynamics along curved ferromagnetic strips is studied by coupling the magnetization dynamics to the heat transport. Permalloy strips with uniform and non-uniform cross section are evaluated, taking into account the influence of the electrical contacts used to inject the current pulses and the substrate on top of which the ferromagnetic strip is sited. Micromagnetic simulations indicate that the geometry and the non-ferromagnetic materials in the system play a significant role in the current-induced domain wall dynamics. Due to the natural pinning, domain walls are hardly affected by the spin-transfer torques when placed in uniform cross section strips under current pulses with reduced magnitude. On the contrary, the current-induced domain wall displacement is significantly different in strips with non-uniform cross section, where thermal gradients emerge as due to the Joule heating. It is found that these thermal gradients can assist or act against the pure spin-transfer torques, in agreement with the recent experimental observations.

  12. Resistance of domain walls created by means of a magnetic force microscope in transversally magnetized epitaxial Fe wires

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

    Hassel, C.; Stienen, S.; Roemer, F. M.

    2009-07-20

    Magnetic domain walls are created in a controllable way in transversally magnetized epitaxial Fe wires on GaAs(110) by approaching a magnetic force microscope (MFM) tip. The electrical resistance-change due to the addition of these domain walls is measured. The anisotropic magnetoresistance as well as the intrinsic domain wall resistance contribute to the resistance-change. The efficiency of this procedure is proven by MFM images, which are obtained subsequent to the domain wall creation at a larger sample-to-probe distance. The contribution of the anisotropic magnetoresistance is calculated using micromagnetic calculations, thus making it possible to quantify the intrinsic domain wall resistance.

  13. Effects of biases in domain wall network evolution. II. Quantitative analysis

    NASA Astrophysics Data System (ADS)

    Correia, J. R. C. C. C.; Leite, I. S. C. R.; Martins, C. J. A. P.

    2018-04-01

    Domain walls form at phase transitions which break discrete symmetries. In a cosmological context, they often overclose the Universe (contrary to observational evidence), although one may prevent this by introducing biases or forcing anisotropic evolution of the walls. In a previous work [Correia et al., Phys. Rev. D 90, 023521 (2014), 10.1103/PhysRevD.90.023521], we numerically studied the evolution of various types of biased domain wall networks in the early Universe, confirming that anisotropic networks ultimately reach scaling while those with a biased potential or biased initial conditions decay. We also found that the analytic decay law obtained by Hindmarsh was in good agreement with simulations of biased potentials, but not of biased initial conditions, and suggested that the difference was related to the Gaussian approximation underlying the analytic law. Here, we extend our previous work in several ways. For the cases of biased potential and biased initial conditions, we study in detail the field distributions in the simulations, confirming that the validity (or not) of the Gaussian approximation is the key difference between the two cases. For anisotropic walls, we carry out a more extensive set of numerical simulations and compare them to the canonical velocity-dependent one-scale model for domain walls, finding that the model accurately predicts the linear scaling regime after isotropization. Overall, our analysis provides a quantitative description of the cosmological evolution of these networks.

  14. Conformational dynamics and ligand binding in the multi-domain protein PDC109.

    PubMed

    Kim, Hyun Jin; Choi, Moo Young; Kim, Hyung J; Llinás, Miguel

    2010-02-18

    PDC109 is a modular multi-domain protein with two fibronectin type II (Fn2) repeats joined by a linker. It plays a major role in bull sperm binding to the oviductal epithelium through its interactions with phosphorylcholines (PhCs), a head group of sperm cell membrane lipids. The crystal structure of the PDC109-PhC complex shows that each PhC binds to the corresponding Fn2 domain, while the two domains are on the same face of the protein. Long timescale explicit solvent molecular dynamics (MD) simulations of PDC109, in the presence and absence of PhC, suggest that PhC binding strongly correlates with the relative orientation of choline-phospholipid binding sites of the two Fn2 domains; unless the two domains tightly bind PhCs, they tend to change their relative orientation by deforming the flexible linker. The effective PDC109-PhC association constant of 28 M(-1), estimated from their potential of mean force is consistent with the experimental result. Principal component analysis of the long timescale MD simulations was compared to the significantly less expensive normal mode analysis of minimized structures. The comparison indicates that difference between relative domain motions of PDC109 with bound and unbound PhC is captured by the first principal component in the principal component analysis as well as the three lowest normal modes in the normal mode analysis. The present study illustrates the use of detailed MD simulations to clarify the energetics of specific ligand-domain interactions revealed by a static crystallographic model, as well as their influence on relative domain motions in a multi-domain protein.

  15. Energy-efficient writing scheme for magnetic domain-wall motion memory

    NASA Astrophysics Data System (ADS)

    Kim, Kab-Jin; Yoshimura, Yoko; Ham, Woo Seung; Ernst, Rick; Hirata, Yuushou; Li, Tian; Kim, Sanghoon; Moriyama, Takahiro; Nakatani, Yoshinobu; Ono, Teruo

    2017-04-01

    We present an energy-efficient magnetic domain-writing scheme for domain wall (DW) motion-based memory devices. A cross-shaped nanowire is employed to inject a domain into the nanowire through current-induced DW propagation. The energy required for injecting the magnetic domain is more than one order of magnitude lower than that for the conventional field-based writing scheme. The proposed scheme is beneficial for device miniaturization because the threshold current for DW propagation scales with the device size, which cannot be achieved in the conventional field-based technique.

  16. In-Solution SH2 Domain Binding Assay Based on Proximity Ligation.

    PubMed

    Machida, Kazuya

    2017-01-01

    Protein-protein interactions mediated by SH2 domains confer specificity in tyrosine kinase pathways. Traditional assays for assessing interactions between an SH2 domain and its interacting protein such as far-Western and pull-down are inherently low throughput. We developed SH2-PLA, an in-solution SH2 domain binding assay, that takes advantage of the speed and sensitivity of proximity ligation and real-time PCR. SH2-PLA allows for rapid assessment of SH2 domain binding to a target protein using only a few microliters of cell lysate, thereby making it an attractive new tool to study tyrosine kinase signaling.

  17. Ligand Binding to WW Tandem Domains of YAP2 Transcriptional Regulator Is Under Negative Cooperativity

    PubMed Central

    Schuchardt, Brett J.; Mikles, David C.; Hoang, Lawrence M.; Bhat, Vikas; McDonald, Caleb B.; Sudol, Marius; Farooq, Amjad

    2014-01-01

    YAP2 transcriptional regulator drives a multitude of cellular processes, including the newly discovered Hippo tumor suppressor pathway, by virtue of the ability of its WW domains to bind and recruit PPXY-containing ligands to specific subcellular compartments. Herein, we employ an array of biophysical tools to investigate allosteric communication between the WW tandem domains of YAP2. Our data show that the WW tandem domains of YAP2 negatively cooperate when binding to their cognate ligands. Moreover, the molecular origin of such negative cooperativity lies in an unfavorable entropic contribution to the overall free energy relative to ligand binding to isolated WW domains. Consistent with this notion, the WW tandem domains adopt a fixed spatial orientation such that the WW1 domain curves outwards and stacks onto the binding groove of WW2 domain, thereby sterically hindering ligand binding to both itself and its tandem partner. Although ligand binding to both WW domains disrupts such interdomain stacking interaction, they reorient themselves and adopt an alternative fixed spatial orientation in the liganded state by virtue of their ability to engage laterally so as to allow their binding grooves to point outwards and away from each other. In short, while the ability of WW tandem domains to aid ligand binding is well-documented, our demonstration that they may also be subject to negative binding cooperativity represents a paradigm shift in our understanding of the molecular action of this ubiquitous family of protein modules. PMID:25283809

  18. Δmix parameter in the overlap on domain-wall mixed action

    NASA Astrophysics Data System (ADS)

    Lujan, M.; Alexandru, A.; Chen, Y.; Draper, T.; Freeman, W.; Gong, M.; Lee, F. X.; Li, A.; Liu, K. F.; Mathur, N.

    2012-07-01

    A direct calculation of the mixed action parameter Δmix with valence overlap fermions on a domain-wall fermion sea is presented. The calculation is performed on four ensembles of the 2+1 flavor domain-wall gauge configurations: 243×64 (aml=0.005, a=0.114fm) and 323×64 (aml=0.004, 0.006, 0.008, a=0.085fm). For pion masses close to 300 MeV we find Δmix=0.030(6)GeV4 at a=0.114fm and Δmix=0.033(12)GeV4 at a=0.085fm. The results are quite independent of the lattice spacing and they are significantly smaller than the results for valence domain-wall fermions on asqtad sea or those of valence overlap fermions on clover sea. Combining the results extracted from these two ensembles, we get Δmix=0.030(6)(5)GeV4, where the first error is statistical and the second is the systematic error associated with the fitting method.

  19. Domain Wall Fermion Inverter on Pentium 4

    NASA Astrophysics Data System (ADS)

    Pochinsky, Andrew

    2005-03-01

    A highly optimized domain wall fermion inverter has been developed as part of the SciDAC lattice initiative. By designing the code to minimize memory bus traffic, it achieves high cache reuse and performance in excess of 2 GFlops for out of L2 cache problem sizes on a GigE cluster with 2.66 GHz Xeon processors. The code uses the SciDAC QMP communication library.

  20. The Toxoplasma gondii cyst wall protein CST1 is critical for cyst wall integrity and promotes bradyzoite persistence

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

    Tomita, Tadakimi; Bzik, David J.; Ma, Yan Fen

    2013-12-26

    Toxoplasma gondii infects up to one third of the world’s population. A key to the success of T.gondii is its ability to persist for the life of its host as bradyzoites within tissue cysts. The glycosylated cyst wall is the key structural feature that facilitates persistence and oral transmission of this parasite. We have identified CST1 (TGME49_064660) as a 250 kDa SRS (SAG1 related sequence) domain protein with a large mucin-like domain. CST1 is responsible for the Dolichos biflorus Agglutinin (DBA) lectin binding characteristic of T. gondii cysts. Deletion of CST1 results in a fragile brain cyst phenotype revealed bymore » a thinning and disruption of the underlying region of the cyst wall. These defects are reversed by complementation of CST1. Additional complementation experiments demonstrate that the CST1-mucin domain is necessary for the formation of a normal cyst wall structure, the ability of the cyst to resist mechanical stress and binding of DBA to the cyst wall. RNA-seq transcriptome analysis demonstrated dysregulation of bradyzoite genes within the various cst1 mutants. These results indicate that CST1 functions as a key structural component that reinforces the cyst wall structure and confers essential sturdiness to the T. gondii tissue cyst.« less

  1. Quantitative relation between intermolecular and intramolecular binding of pro-rich peptides to SH3 domains.

    PubMed

    Zhou, Huan-Xiang

    2006-11-01

    Flexible linkers are often found to tether binding sequence motifs or connect protein domains. Here we analyze three usages of flexible linkers: 1), intramolecular binding of proline-rich peptides (PRPs) to SH3 domains for kinase regulation; 2), intramolecular binding of PRP for increasing the folding stability of SH3 domains; and 3), covalent linking of PRPs and other ligands for high-affinity bivalent binding. The basis of these analyses is a quantitative relation between intermolecular and intramolecular binding constants. This relation has the form K(i) = K(e0)p for intramolecular binding and K(e) = K(e01)K(e02)p for bivalent binding. The effective concentration p depends on the length of the linker and the distance between the linker attachment points in the bound state. Several applications illustrate the usefulness of the quantitative relation. These include intramolecular binding to the Itk SH3 domain by an internal PRP and to a circular permutant of the alpha-spectrin SH3 domain by a designed PRP, and bivalent binding to the two SH3 domains of Grb2 by two linked PRPs. These and other examples suggest that flexible linkers and sequence motifs tethered to them, like folded protein domains, are also subject to tight control during evolution.

  2. Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains.

    PubMed

    Herbig, Eric; Warfield, Linda; Fish, Lisa; Fishburn, James; Knutson, Bruce A; Moorefield, Beth; Pacheco, Derek; Hahn, Steven

    2010-05-01

    Targets of the tandem Gcn4 acidic activation domains in transcription preinitiation complexes were identified by site-specific cross-linking. The individual Gcn4 activation domains cross-link to three common targets, Gal11/Med15, Taf12, and Tra1, which are subunits of four conserved coactivator complexes, Mediator, SAGA, TFIID, and NuA4. The Gcn4 N-terminal activation domain also cross-links to the Mediator subunit Sin4/Med16. The contribution of the two Gcn4 activation domains to transcription was gene specific and varied from synergistic to less than additive. Gcn4-dependent genes had a requirement for Gal11 ranging from 10-fold dependence to complete Gal11 independence, while the Gcn4-Taf12 interaction did not significantly contribute to the expression of any gene studied. Complementary methods identified three conserved Gal11 activator-binding domains that bind each Gcn4 activation domain with micromolar affinity. These Gal11 activator-binding domains contribute additively to transcription activation and Mediator recruitment at Gcn4- and Gal11-dependent genes. Although we found that the conserved Gal11 KIX domain contributes to Gal11 function, we found no evidence of specific Gcn4-KIX interaction and conclude that the Gal11 KIX domain does not function by specific interaction with Gcn4. Our combined results show gene-specific coactivator requirements, a surprising redundancy in activator-target interactions, and an activator-coactivator interaction mediated by multiple low-affinity protein-protein interactions.

  3. Binding of /sup 18/F by cell membranes and cell walls of Streptococcus mutans

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

    Yotis, W.W.; Zeb, M.; McNulty, J.

    1983-07-01

    The binding of /sup 18/F to isolated cell membranes and cell walls of Streptococcus mutans GS-5 or other bacteria was assayed. The attachment of /sup 18/F to these cell envelopes proceeded slowly and reached equilibrium within 60 min. /sup 18/F binding was stimulated by Ca/sup 2 +/ (1 mM). The binding of /sup 18/F to cellular components was dependent upon the pH, as well as the amount of /sup 18/F and dose of the binder employed. The binding of /sup 18/F by cell walls prepared from fluoride-sensitive and fluoride-resistant cells of S. salivarius and S. mutans did not differ significantly.more » The pretreatment of cell walls or cell membranes for 60 min at 30 degrees C with 1 mg of RNase, DNase, or trypsin per ml did not influence the binding of /sup 18/F by the walls and membranes of S. mutans GS-5. However, prior exposure of cell membranes to sodium dodecyl sulfate caused a significant reduction in the number of /sup 18/F atoms bound by the membranes. In saturated assay systems, cell membranes of S. mutans GS-5 bound 10(15) to 10(16) atoms of /sup 18/F per mg (dry weight), whereas cell walls from S. mutans GS-5, FA-1, and HS-6 or Actinomyces viscosus T14V and T14AV bound 10(12) to 10(13) atoms of /sup 18/F per mg (dry weight). /sup 18/F in this quantity (10(12) to 10(13) atoms) cannot be detected with the fluoride electrode. The data provide, for the first time, a demonstration of /sup 18/F binding by cell membranes and walls of oral flora.« less

  4. Domain-wall guided nucleation of superconductivity in hybrid ferromagnet-superconductor-ferromagnet layered structures.

    PubMed

    Gillijns, W; Aladyshkin, A Yu; Lange, M; Van Bael, M J; Moshchalkov, V V

    2005-11-25

    Domain-wall superconductivity is studied in a superconducting Nb film placed between two ferromagnetic Co/Pd multilayers with perpendicular magnetization. The parameters of top and bottom ferromagnetic films are chosen to provide different coercive fields, so that the magnetic domain structure of the ferromagnets can be selectively controlled. From the dependence of the critical temperature Tc on the applied magnetic field H, we have found evidence for domain-wall superconductivity in this three-layered F/S/F structure for different magnetic domain patterns. The phase boundary, calculated numerically for this structure from the linearized Ginzburg-Landau equation, is in good agreement with the experimental data.

  5. Extended HSR/CARD domain mediates AIRE binding to DNA

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

    Maslovskaja, Julia, E-mail: julia.maslovskaja@ut.ee; Saare, Mario; Liiv, Ingrid

    Autoimmune regulator (AIRE) activates the transcription of many genes in an unusual promiscuous and stochastic manner. The mechanism by which AIRE binds to the chromatin and DNA is not fully understood, and the regulatory elements that AIRE target genes possess are not delineated. In the current study, we demonstrate that AIRE activates the expression of transiently transfected luciferase reporters that lack defined promoter regions, as well as intron and poly(A) signal sequences. Our protein-DNA interaction experiments with mutated AIRE reveal that the intact homogeneously staining region/caspase recruitment domain (HSR/CARD) and amino acids R113 and K114 are key elements involved inmore » AIRE binding to DNA. - Highlights: • Promoter and mRNA processing elements are not important for AIRE to activate gene expression from reporter plasmids. • AIRE protein fragment aa 1–138 mediates direct binding to DNA. • Integrity of the HSR/CARD domain is needed for AIRE binding to DNA.« less

  6. Evolution of domain walls in the early universe. Ph.D. Thesis - Chicago Univ.

    NASA Technical Reports Server (NTRS)

    Kawano, Lawrence

    1989-01-01

    The evolution of domain walls in the early universe is studied via 2-D computer simulation. The walls are initially configured on a triangular lattice and then released from the lattice, their evolution driven by wall curvature and by the universal expansion. The walls attain an average velocity of about 0.3c and their surface area per volume (as measured in comoving coordinates) goes down with a slope of -1 with respect to conformal time, regardless of whether the universe is matter or radiation dominated. The additional influence of vacuum pressure causes the energy density to fall away from this slope and steepen, thus allowing a situation in which domain walls can constitute a significant portion of the energy density of the universe without provoking an unacceptably large perturbation upon the microwave background.

  7. Solution structure of telomere binding domain of AtTRB2 derived from Arabidopsis thaliana

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

    Yun, Ji-Hye; Lee, Won Kyung; Kim, Heeyoun

    Highlights: • We have determined solution structure of Myb domain of AtTRB2. • The Myb domain of AtTRB2 is located in the N-terminal region. • The Myb domain of AtTRB2 binds to plant telomeric DNA without fourth helix. • Helix 2 and 3 of the Myb domain of AtTRB2 are involved in DNA recognition. • AtTRB2 is a novel protein distinguished from other known plant TBP. - Abstract: Telomere homeostasis is regulated by telomere-associated proteins, and the Myb domain is well conserved for telomere binding. AtTRB2 is a member of the SMH (Single-Myb-Histone)-like family in Arabidopsis thaliana, having an N-terminalmore » Myb domain, which is responsible for DNA binding. The Myb domain of AtTRB2 contains three α-helices and loops for DNA binding, which is unusual given that other plant telomere-binding proteins have an additional fourth helix that is essential for DNA binding. To understand the structural role for telomeric DNA binding of AtTRB2, we determined the solution structure of the Myb domain of AtTRB2 (AtTRB2{sub 1–64}) using nuclear magnetic resonance (NMR) spectroscopy. In addition, the inter-molecular interaction between AtTRB2{sub 1–64} and telomeric DNA has been characterized by the electrophoretic mobility shift assay (EMSA) and NMR titration analyses for both plant (TTTAGGG)n and human (TTAGGG)n telomere sequences. Data revealed that Trp28, Arg29, and Val47 residues located in Helix 2 and Helix 3 are crucial for DNA binding, which are well conserved among other plant telomere binding proteins. We concluded that although AtTRB2 is devoid of the additional fourth helix in the Myb-extension domain, it is able to bind to plant telomeric repeat sequences as well as human telomeric repeat sequences.« less

  8. The structure of the nucleoprotein binding domain of lyssavirus phosphoprotein reveals a structural relationship between the N-RNA binding domains of Rhabdoviridae and Paramyxoviridae.

    PubMed

    Delmas, Olivier; Assenberg, Rene; Grimes, Jonathan M; Bourhy, Hervé

    2010-01-01

    The phosphoprotein P of non-segmented negative-sense RNA viruses is an essential component of the replication and transcription complex and acts as a co-factor for the viral RNA-dependent RNA polymerase. P recruits the viral polymerase to the nucleoprotein-bound viral RNA (N-RNA) via an interaction between its C-terminal domain and the N-RNA complex. We have obtained the structure of the C-terminal domain of P of Mokola virus (MOKV), a lyssavirus that belongs to the Rhabdoviridae family and mapped at the amino acid level the crucial positions involved in interaction with N and in the formation of the viral replication complex. Comparison of the N-RNA binding domains of P solved to date suggests that the N-RNA binding domains are structurally conserved among paramyxoviruses and rhabdoviruses in spite of low sequence conservation. We also review the numerous other functions of this domain and more generally of the phosphoprotein.

  9. The stability of steady motion of magnetic domain wall: Role of higher-order spin-orbit torques

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

    He, Peng-Bin, E-mail: hepengbin@hnu.edu.cn; Yan, Han; Cai, Meng-Qiu

    The steady motion of magnetic domain wall driven by spin-orbit torques is investigated analytically in the heavy/ferromagnetic metal nanowires for three cases with a current transverse to the in-plane and perpendicular easy axis, and along the in-plane easy axis. By the stability analysis of Walker wall profile, we find that if including the higher-order spin-orbit torques, the Walker breakdown can be avoided in some parameter regions of spin-orbit torques with a current transverse to or along the in-plane easy axis. However, in the case of perpendicular anisotropy, even considering the higher-order spin-orbit torques, the velocity of domain wall cannot bemore » efficiently enhanced by the current. Furthermore, the direction of wall motion is dependent on the configuration and chirality of domain wall with a current along the in-plane easy axis or transverse to the perpendicular one. Especially, the direction of motion can be controlled by the initial chirality of domain wall. So, if only involving the spin-orbit mechanism, it is preferable to adopt the scheme of a current along the in-plane easy axis for enhancing the velocity and controlling the direction of domain wall.« less

  10. Ligand binding to WW tandem domains of YAP2 transcriptional regulator is under negative cooperativity.

    PubMed

    Schuchardt, Brett J; Mikles, David C; Hoang, Lawrence M; Bhat, Vikas; McDonald, Caleb B; Sudol, Marius; Farooq, Amjad

    2014-12-01

    YES-associated protein 2 (YAP2) transcriptional regulator drives a multitude of cellular processes, including the newly discovered Hippo tumor suppressor pathway, by virtue of the ability of its WW domains to bind and recruit PPXY-containing ligands to specific subcellular compartments. Herein, we employ an array of biophysical tools to investigate allosteric communication between the WW tandem domains of YAP2. Our data show that the WW tandem domains of YAP2 negatively cooperate when binding to their cognate ligands. Moreover, the molecular origin of such negative cooperativity lies in an unfavorable entropic contribution to the overall free energy relative to ligand binding to isolated WW domains. Consistent with this notion, the WW tandem domains adopt a fixed spatial orientation such that the WW1 domain curves outwards and stacks onto the binding groove of the WW2 domain, thereby sterically hindering ligand binding to both itself and its tandem partner. Although ligand binding to both WW domains disrupts such interdomain stacking interaction, they reorient themselves and adopt an alternative fixed spatial orientation in the liganded state by virtue of their ability to engage laterally so as to allow their binding grooves to point outwards and away from each other. In short, while the ability of WW tandem domains to aid ligand binding is well documented, our demonstration that they may also be subject to negative binding cooperativity represents a paradigm shift in our understanding of the molecular action of this ubiquitous family of protein modules. © 2014 FEBS.

  11. Raman signatures of ferroic domain walls captured by principal component analysis.

    PubMed

    Nataf, G F; Barrett, N; Kreisel, J; Guennou, M

    2018-01-24

    Ferroic domain walls are currently investigated by several state-of-the art techniques in order to get a better understanding of their distinct, functional properties. Here, principal component analysis (PCA) of Raman maps is used to study ferroelectric domain walls (DWs) in LiNbO 3 and ferroelastic DWs in NdGaO 3 . It is shown that PCA allows us to quickly and reliably identify small Raman peak variations at ferroelectric DWs and that the value of a peak shift can be deduced-accurately and without a priori-from a first order Taylor expansion of the spectra. The ability of PCA to separate the contribution of ferroelastic domains and DWs to Raman spectra is emphasized. More generally, our results provide a novel route for the statistical analysis of any property mapped across a DW.

  12. Hydrolysis at One of the Two Nucleotide-binding Sites Drives the Dissociation of ATP-binding Cassette Nucleotide-binding Domain Dimers

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

    Zoghbi, M. E.; Altenberg, G. A.

    The functional unit of ATP-binding cassette (ABC) transporters consists of two transmembrane domains and two nucleotide-binding domains (NBDs). ATP binding elicits association of the two NBDs, forming a dimer in a head-to-tail arrangement, with two nucleotides “sandwiched” at the dimer interface. Each of the two nucleotide-binding sites is formed by residues from the two NBDs. We recently found that the prototypical NBD MJ0796 from Methanocaldococcus jannaschii dimerizes in response to ATP binding and dissociates completely following ATP hydrolysis. However, it is still unknown whether dissociation of NBD dimers follows ATP hydrolysis at one or both nucleotide-binding sites. Here, we usedmore » luminescence resonance energy transfer to study heterodimers formed by one active (donor-labeled) and one catalytically defective (acceptor-labeled) NBD. Rapid mixing experiments in a stop-flow chamber showed that NBD heterodimers with one functional and one inactive site dissociated at a rate indistinguishable from that of dimers with two hydrolysis-competent sites. Comparison of the rates of NBD dimer dissociation and ATP hydrolysis indicated that dissociation followed hydrolysis of one ATP. We conclude that ATP hydrolysis at one nucleotide-binding site drives NBD dimer dissociation.« less

  13. A Novel Kinesin-Like Protein with a Calmodulin-Binding Domain

    NASA Technical Reports Server (NTRS)

    Wang, W.; Takezawa, D.; Narasimhulu, S. B.; Reddy, A. S. N.; Poovaiah, B. W.

    1996-01-01

    Calcium regulates diverse developmental processes in plants through the action of calmodulin. A cDNA expression library from developing anthers of tobacco was screened with S-35-labeled calmodulin to isolate cDNAs encoding calmodulin-binding proteins. Among several clones isolated, a kinesin-like gene (TCK1) that encodes a calmodulin-binding kinesin-like protein was obtained. The TCK1 cDNA encodes a protein with 1265 amino acid residues. Its structural features are very similar to those of known kinesin heavy chains and kinesin-like proteins from plants and animals, with one distinct exception. Unlike other known kinesin-like proteins, TCK1 contains a calmodulin-binding domain which distinguishes it from all other known kinesin genes. Escherichia coli-expressed TCK1 binds calmodulin in a Ca(2+)-dependent manner. In addition to the presence of a calmodulin-binding domain at the carboxyl terminal, it also has a leucine zipper motif in the stalk region. The amino acid sequence at the carboxyl terminal of TCK1 has striking homology with the mechanochemical motor domain of kinesins. The motor domain has ATPase activity that is stimulated by microtubules. Southern blot analysis revealed that TCK1 is coded by a single gene. Expression studies indicated that TCKI is expressed in all of the tissues tested. Its expression is highest in the stigma and anther, especially during the early stages of anther development. Our results suggest that Ca(2+)/calmodulin may play an important role in the function of this microtubule-associated motor protein and may be involved in the regulation of microtubule-based intracellular transport.

  14. Stability and Sugar Recognition Ability of Ricin-Like Carbohydrate Binding Domains

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

    Yao, Jianzhuang; Nellas, Ricky B; Glover, Mary M

    2011-01-01

    Lectins are a class of proteins known for their novel binding to saccharides. Understanding this sugar recognition process can be crucial in creating structure-based designs of proteins with various biological roles. We focus on the sugar binding of a particular lectin, ricin, which has two -trefoil carbohydrate-binding domains (CRDs) found in several plant protein toxins. The binding ability of possible sites of ricin-like CRD has been puzzling. The apo and various (multiple) ligand-bound forms of the sugar-binding domains of ricin were studied by molecular dynamics simulations. By evaluating structural stability, hydrogen bond dynamics, flexibility, and binding energy, we obtained amore » detailed picture of the sugar recognition of the ricin-like CRD. Unlike what was previously believed, we found that the binding abilities of the two known sites are not independent of each other. The binding ability of one site is positively affected by the other site. While the mean positions of different binding scenarios are not altered significantly, the flexibility of the binding pockets visibly decreases upon multiple ligand binding. This change in flexibility seems to be the origin of the binding cooperativity. All the hydrogen bonds that are strong in the monoligand state are also strong in the double-ligand complex, although the stability is much higher in the latter form due to cooperativity. These strong hydrogen bonds in a monoligand state are deemed to be the essential hydrogen bonds. Furthermore, by examining the structural correlation matrix, the two domains are structurally one entity. Galactose hydroxyl groups, OH4 and OH3, are the most critical parts in both site 1 and site 2 recognition.« less

  15. Matter antimatter domains: A possible solution to the CP domain wall problem in the early universe

    NASA Technical Reports Server (NTRS)

    Mohanty, A. K.; Stecker, F. W.

    1984-01-01

    An SU(5) grand unified theory model is used to show how the degeneracy between vacua with different spontaneously broken charge parity can be dynamically lifted by a condensate of heavy fermion pairs. This drives a phase transition to a unique vacuum state with definite charge parity. The transition eliminates the domain walls in a matter antimatter symmetric domain cosmology.

  16. Stabilization of domain walls between traveling waves by nonlinear mode coupling in Taylor-Couette flow.

    PubMed

    Heise, M; Hoffmann, Ch; Abshagen, J; Pinter, A; Pfister, G; Lücke, M

    2008-02-15

    We present a new mechanism that allows the stable existence of domain walls between oppositely traveling waves in pattern-forming systems far from onset. It involves a nonlinear mode coupling that results directly from the nonlinearities in the underlying momentum balance. Our work provides the first observation and explanation of such strongly nonlinearly driven domain walls that separate structured states by a phase generating or annihilating defect. Furthermore, the influence of a symmetry breaking externally imposed flow on the wave domains and the domain walls is studied. The results are obtained for vortex waves in the Taylor-Couette system by combining numerical simulations of the full Navier-Stokes equations and experimental measurements.

  17. First-Principles Calculations of Current-Induced Spin-Transfer Torques in Magnetic Domain Walls

    NASA Astrophysics Data System (ADS)

    Tang, Ling; Xu, Zhijun; Yang, Zejin

    2013-05-01

    Current-induced spin-transfer torques (STTs) have been studied in Fe, Co and Ni domain walls (DWs) by the method based on the first-principles noncollinear calculations of scattering wavefunctions expanded in the tight-binding linearized muffin-tin orbital (TB-LMTO) basis. The results show that the out-of-plane component of nonadiabatic STT in Fe DW has localized form, which is in contrast to the typical nonlocal oscillating nonadiabatic torques obtained in Co and Ni DWs. Meanwhile, the degree of nonadiabaticity in STT is also much greater for Fe DW. Further, our results demonstrate that compared to the well-known first-order nonadiabatic STT, the torque in the third-order spatial derivative of local spin can better describe the distribution of localized nonadiabatic STT in Fe DW. The dynamics of local spin driven by this third-order torques in Fe DW have been investigated by the Landau-Lifshitz-Gilbert (LLG) equation. The calculated results show that with the same amplitude of STTs the DW velocity induced by this third-order term is about half of the wall speed for the case of the first-order nonadiabatic STT.

  18. Carbohydrate-dependent binding of langerin to SodC, a cell wall glycoprotein of Mycobacterium leprae.

    PubMed

    Kim, Hee Jin; Brennan, Patrick J; Heaslip, Darragh; Udey, Mark C; Modlin, Robert L; Belisle, John T

    2015-02-01

    Langerhans cells participate in the immune response in leprosy by their ability to activate T cells that recognize the pathogen, Mycobacterium leprae, in a langerin-dependent manner. We hypothesized that langerin, the distinguishing C-type lectin of Langerhans cells, would recognize the highly mannosylated structures in pathogenic Mycobacterium spp. The coding region for the extracellular and neck domain of human langerin was cloned and expressed to produce a recombinant active trimeric form of human langerin (r-langerin). Binding assays performed in microtiter plates, by two-dimensional (2D) Western blotting, and by surface plasmon resonance demonstrated that r-langerin possessed carbohydrate-dependent affinity to glycoproteins in the cell wall of M. leprae. This lectin, however, yielded less binding to mannose-capped lipoarabinomannan (ManLAM) and even lower levels of binding to phosphatidylinositol mannosides. However, the superoxide dismutase C (SodC) protein of the M. leprae cell wall was identified as a langerin-reactive ligand. Tandem mass spectrometry verified the glycosylation of a recombinant form of M. leprae SodC (rSodC) produced in Mycobacterium smegmatis. Analysis of r-langerin affinity by surface plasmon resonance revealed a carbohydrate-dependent affinity of rSodC (equilibrium dissociation constant [KD] = 0.862 μM) that was 20-fold greater than for M. leprae ManLAM (KD = 18.69 μM). These data strongly suggest that a subset of the presumptively mannosylated M. leprae glycoproteins act as ligands for langerin and may facilitate the interaction of M. leprae with Langerhans cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. Carbohydrate-Dependent Binding of Langerin to SodC, a Cell Wall Glycoprotein of Mycobacterium leprae

    PubMed Central

    Kim, Hee Jin; Brennan, Patrick J.; Heaslip, Darragh; Udey, Mark C.; Modlin, Robert L.

    2014-01-01

    Langerhans cells participate in the immune response in leprosy by their ability to activate T cells that recognize the pathogen, Mycobacterium leprae, in a langerin-dependent manner. We hypothesized that langerin, the distinguishing C-type lectin of Langerhans cells, would recognize the highly mannosylated structures in pathogenic Mycobacterium spp. The coding region for the extracellular and neck domain of human langerin was cloned and expressed to produce a recombinant active trimeric form of human langerin (r-langerin). Binding assays performed in microtiter plates, by two-dimensional (2D) Western blotting, and by surface plasmon resonance demonstrated that r-langerin possessed carbohydrate-dependent affinity to glycoproteins in the cell wall of M. leprae. This lectin, however, yielded less binding to mannose-capped lipoarabinomannan (ManLAM) and even lower levels of binding to phosphatidylinositol mannosides. However, the superoxide dismutase C (SodC) protein of the M. leprae cell wall was identified as a langerin-reactive ligand. Tandem mass spectrometry verified the glycosylation of a recombinant form of M. leprae SodC (rSodC) produced in Mycobacterium smegmatis. Analysis of r-langerin affinity by surface plasmon resonance revealed a carbohydrate-dependent affinity of rSodC (equilibrium dissociation constant [KD] = 0.862 μM) that was 20-fold greater than for M. leprae ManLAM (KD = 18.69 μM). These data strongly suggest that a subset of the presumptively mannosylated M. leprae glycoproteins act as ligands for langerin and may facilitate the interaction of M. leprae with Langerhans cells. PMID:25422308

  20. Is the isolated ligand binding domain a good model of the domain in the native receptor?

    PubMed

    Deming, Dustin; Cheng, Qing; Jayaraman, Vasanthi

    2003-05-16

    Numerous studies have used the atomic level structure of the isolated ligand binding domain of the glutamate receptor to elucidate the agonist-induced activation and desensitization processes in this group of proteins. However, no study has demonstrated the structural equivalence of the isolated ligand binding fragments and the protein in the native receptor. In this report, using visible absorption spectroscopy we show that the electronic environment of the antagonist 6-cyano-7-nitro-2,3-dihydroxyquinoxaline is identical for the isolated protein and the native glutamate receptors expressed in cells. Our results hence establish that the local structure of the ligand binding site is the same in the two proteins and validate the detailed structure-function relationships that have been developed based on a comparison of the structure of the isolated ligand binding domain and electrophysiological consequences in the native receptor.

  1. Akt1 binds focal adhesion kinase via the Akt1 kinase domain independently of the pleckstrin homology domain.

    PubMed

    Basson, M D; Zeng, B; Wang, S

    2015-10-01

    Akt1 and focal adhesion kinase (FAK) are protein kinases that play key roles in normal cell signaling. Individually, aberrant expression of these kinases has been linked to a variety of cancers. Together, Akt1/FAK interactions facilitate cancer metastasis by increasing cell adhesion under conditions of increased extracellular pressure. Pathological and iatrogenic sources of pressure arise from tumor growth against constraining stroma or direct perioperative manipulation. We previously reported that 15 mmHg increased extracellular pressure causes Akt1 to both directly interact with FAK and to phosphorylate and activate it. We investigated the nature of the Akt1/FAK binding by creating truncations of recombinant FAK, conjugated to glutathione S-transferase (GST), to pull down full-length Akt1. Western blots probing for Akt1 showed that FAK/Akt1 binding persisted in FAK truncations consisting of only amino acids 1-126, FAK(NT1), which contains the F1 subdomain of its band 4.1, ezrin, radixin, and moesin (FERM) domain. Using FAK(NT1) as bait, we then pulled down truncated versions of recombinant Akt1 conjugated to HA (human influenza hemagglutinin). Probes for GST-FAK(NT1) showed Akt1-FAK binding to occur in the absence of the both the Akt1 (N)-terminal pleckstrin homology (PH) domain and its adjacent hinge region. The Akt1 (C)-terminal regulatory domain was equally unnecessary for Akt1/FAK co-immunoprecipitation. Truncations involving the Akt1 catalytic domain showed that the domain by itself was enough to pull down FAK. Additionally, a fragment spanning from the PH domain to half way through the catalytic domain demonstrated increased FAK binding compared to full length Akt1. These results begin to delineate the Akt1/FAK interaction and can be used to manipulate their force-activated signal interactions. Furthermore, the finding that the N-terminal half of the Akt1 catalytic domain binds so strongly to FAK when cleaved from the rest of the protein may suggest a means

  2. The CRM domain: an RNA binding module derived from an ancient ribosome-associated protein.

    PubMed

    Barkan, Alice; Klipcan, Larik; Ostersetzer, Oren; Kawamura, Tetsuya; Asakura, Yukari; Watkins, Kenneth P

    2007-01-01

    The CRS1-YhbY domain (also called the CRM domain) is represented as a stand-alone protein in Archaea and Bacteria, and in a family of single- and multidomain proteins in plants. The function of this domain is unknown, but structural data and the presence of the domain in several proteins known to interact with RNA have led to the proposal that it binds RNA. Here we describe a phylogenetic analysis of the domain, its incorporation into diverse proteins in plants, and biochemical properties of a prokaryotic and eukaryotic representative of the domain family. We show that a bacterial member of the family, Escherichia coli YhbY, is associated with pre-50S ribosomal subunits, suggesting that YhbY functions in ribosome assembly. GFP fused to a single-domain CRM protein from maize localizes to the nucleolus, suggesting that an analogous activity may have been retained in plants. We show further that an isolated maize CRM domain has RNA binding activity in vitro, and that a small motif shared with KH RNA binding domains, a conserved "GxxG" loop, contributes to its RNA binding activity. These and other results suggest that the CRM domain evolved in the context of ribosome function prior to the divergence of Archaea and Bacteria, that this function has been maintained in extant prokaryotes, and that the domain was recruited to serve as an RNA binding module during the evolution of plant genomes.

  3. Quantitation of the calcium and membrane binding properties of the C2 domains of dysferlin.

    PubMed

    Abdullah, Nazish; Padmanarayana, Murugesh; Marty, Naomi J; Johnson, Colin P

    2014-01-21

    Dysferlin is a large membrane protein involved in calcium-triggered resealing of the sarcolemma after injury. Although it is generally accepted that dysferlin is Ca(2+) sensitive, the Ca(2+) binding properties of dysferlin have not been characterized. In this study, we report an analysis of the Ca(2+) and membrane binding properties of all seven C2 domains of dysferlin as well as a multi-C2 domain construct. Isothermal titration calorimetry measurements indicate that all seven dysferlin C2 domains interact with Ca(2+) with a wide range of binding affinities. The C2A and C2C domains were determined to be the most sensitive, with Kd values in the tens of micromolar, whereas the C2D domain was least sensitive, with a near millimolar Kd value. Mutagenesis of C2A demonstrates the requirement for negatively charged residues in the loop regions for divalent ion binding. Furthermore, dysferlin displayed significantly lower binding affinity for the divalent cations magnesium and strontium. Measurement of a multidomain construct indicates that the solution binding affinity does not change when C2 domains are linked. Finally, sedimentation assays suggest all seven C2 domains bind lipid membranes, and that Ca(2+) enhances but is not required for interaction. This report reveals for the first time, to our knowledge, that all dysferlin domains bind Ca(2+) albeit with varying affinity and stoichiometry. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. The Tyrosine Sulfate Domain of Fibromodulin Binds Collagen and Enhances Fibril Formation.

    PubMed

    Tillgren, Viveka; Mörgelin, Matthias; Önnerfjord, Patrik; Kalamajski, Sebastian; Aspberg, Anders

    2016-11-04

    Small leucine-rich proteoglycans interact with other extracellular matrix proteins and are important regulators of matrix assembly. Fibromodulin has a key role in connective tissues, binding collagen through two identified binding sites in its leucine-rich repeat domain and regulating collagen fibril formation in vitro and in vivo Some nine tyrosine residues in the fibromodulin N-terminal domain are O-sulfated, a posttranslational modification often involved in protein interactions. The N-terminal domain mimics heparin, binding proteins with clustered basic amino acid residues. Because heparin affects collagen fibril formation, we investigated whether tyrosine sulfate is involved in fibromodulin interactions with collagen. Using full-length fibromodulin and its N-terminal tyrosine-sulfated domain purified from tissue, as well as recombinant fibromodulin fragments, we found that the N-terminal domain binds collagen. The tyrosine-sulfated domain and the leucine-rich repeat domain both bound to three specific sites along the collagen type I molecule, at the N terminus and at 100 and 220 nm from the N terminus. The N-terminal domain shortened the collagen fibril formation lag phase and tyrosine sulfation was required for this effect. The isolated leucine-rich repeat domain inhibited the fibril formation rate, and full-length fibromodulin showed a combination of these effects. The fibrils formed in the presence of fibromodulin or its fragments showed more organized structure. Fibromodulin and its tyrosine sulfate domain remained bound on the formed fiber. Taken together, this suggests a novel, regulatory function for tyrosine sulfation in collagen interaction and control of fibril formation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Characterization of the dextran-binding domain in the glucan-binding protein C of Streptococcus mutans.

    PubMed

    Takashima, Y; Fujita, K; Ardin, A C; Nagayama, K; Nomura, R; Nakano, K; Matsumoto-Nakano, M

    2015-10-01

    Streptococcus mutans produces multiple glucan-binding proteins (Gbps), among which GbpC encoded by the gbpC gene is known to be a cell-surface-associated protein involved in dextran-induced aggregation. The purpose of the present study was to characterize the dextran-binding domain of GbpC using bioinformatics analysis and molecular techniques. Bioinformatics analysis specified five possible regions containing molecular binding sites termed GB1 through GB5. Next, truncated recombinant GbpC (rGbpC) encoding each region was produced using a protein expression vector and five deletion mutant strains were generated, termed CDGB1 through CDGB5 respectively. The dextran-binding rates of truncated rGbpC that included the GB1, GB3, GB4 and GB5 regions in the upstream sequences were higher than that of the construct containing GB2 in the downstream region. In addition, the rates of dextran-binding for strains CDGB4 and CD1, which was entire gbpC deletion mutant, were significantly lower than for the other strains, while those of all other deletion mutants were quite similar to that of the parental strain MT8148. Biofilm structures formed by CDGB4 and CD1 were not as pronounced as that of MT8148, while those formed by other strains had greater density as compared to that of CD1. Our results suggest that the dextran-binding domain may be located in the GB4 region in the interior of the gbpC gene. Bioinformatics analysis is useful for determination of functional domains in many bacterial species. © 2015 The Society for Applied Microbiology.

  6. Carbohydrate-binding module 74 is a novel starch-binding domain associated with large and multidomain α-amylase enzymes.

    PubMed

    Valk, Vincent; Lammerts van Bueren, Alicia; van der Kaaij, Rachel M; Dijkhuizen, Lubbert

    2016-06-01

    Microbacterium aurum B8.A is a bacterium that originates from a potato starch-processing plant and employs a GH13 α-amylase (MaAmyA) enzyme that forms pores in potato starch granules. MaAmyA is a large and multi-modular protein that contains a novel domain at its C terminus (Domain 2). Deletion of Domain 2 from MaAmyA did not affect its ability to degrade starch granules but resulted in a strong reduction in granular pore size. Here, we separately expressed and purified this Domain 2 in Escherichia coli and determined its likely function in starch pore formation. Domain 2 independently binds amylose, amylopectin, and granular starch but does not have any detectable catalytic (hydrolytic or oxidizing) activity on α-glucan substrates. Therefore, we propose that this novel starch-binding domain is a new carbohydrate-binding module (CBM), the first representative of family CBM74 that assists MaAmyA in efficient pore formation in starch granules. Protein sequence-based BLAST searches revealed that CBM74 occurs widespread, but in bacteria only, and is often associated with large and multi-domain α-amylases containing family CBM25 or CBM26 domains. CBM74 may specifically function in binding to granular starches to enhance the capability of α-amylase enzymes to degrade resistant starches (RSs). Interestingly, the majority of family CBM74 representatives are found in α-amylases originating from human gut-associated Bifidobacteria, where they may assist in resistant starch degradation. The CBM74 domain thus may have a strong impact on the efficiency of RS digestion in the mammalian gastrointestinal tract. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  7. Mapping the binding domain of the F18 fimbrial adhesin.

    PubMed

    Smeds, A; Pertovaara, M; Timonen, T; Pohjanvirta, T; Pelkonen, S; Palva, A

    2003-04-01

    F18 fimbrial Esherichia coli strains are associated with porcine postweaning diarrhea and pig edema disease. Recently, the FedF subunit was identified as the adhesin of the F18 fimbriae. In this study, adhesion domains of FedF were further studied by constructing deletions within the fedF gene and expressing FedF proteins with deletions either together with the other F18 fimbrial subunits or as fusion proteins tagged with maltose binding protein. The region essential for adhesion to porcine intestinal epithelial cells was mapped between amino acid residues 60 and 109 of FedF. To map the binding domain even more closely, all eight charged amino acid residues within this region were independently replaced by alanine. Three of these single point mutants expressing F18 fimbriae exhibited significantly diminished capabilities to adhere to porcine epithelial cells in vitro. In addition, a triple point mutation and a double point mutation completely abolished receptor adhesiveness. The result further confirmed that the region between amino acid residues 60 and 109 is essential for the binding of F18 fimbriae to their receptor. In addition, the adhesion capability of the binding domain was eliminated after treatment with iodoacetamide, suggesting the formation of a disulfide bridge between Cys-63 and Cys-83, whereas Cys-111 and Cys-116 could be deleted without affecting the binding ability of FedF.

  8. Search for domain wall dark matter with atomic clocks on board global positioning system satellites.

    PubMed

    Roberts, Benjamin M; Blewitt, Geoffrey; Dailey, Conner; Murphy, Mac; Pospelov, Maxim; Rollings, Alex; Sherman, Jeff; Williams, Wyatt; Derevianko, Andrei

    2017-10-30

    Cosmological observations indicate that dark matter makes up 85% of all matter in the universe yet its microscopic composition remains a mystery. Dark matter could arise from ultralight quantum fields that form macroscopic objects. Here we use the global positioning system as a ~ 50,000 km aperture dark matter detector to search for such objects in the form of domain walls. Global positioning system navigation relies on precision timing signals furnished by atomic clocks. As the Earth moves through the galactic dark matter halo, interactions with domain walls could cause a sequence of atomic clock perturbations that propagate through the satellite constellation at galactic velocities ~ 300 km s -1 . Mining 16 years of archival data, we find no evidence for domain walls at our current sensitivity level. This improves the limits on certain quadratic scalar couplings of domain wall dark matter to standard model particles by several orders of magnitude.

  9. Human Hsp70 molecular chaperone binds two calcium ions within the ATPase domain.

    PubMed

    Sriram, M; Osipiuk, J; Freeman, B; Morimoto, R; Joachimiak, A

    1997-03-15

    The 70 kDa heat shock proteins (Hsp70) are a family of molecular chaperones, which promote protein folding and participate in many cellular functions. The Hsp70 chaperones are composed of two major domains. The N-terminal ATPase domain binds to and hydrolyzes ATP, whereas the C-terminal domain is required for polypeptide binding. Cooperation of both domains is needed for protein folding. The crystal structure of bovine Hsc70 ATPase domain (bATPase) has been determined and, more recently, the crystal structure of the peptide-binding domain of a related chaperone, DnaK, in complex with peptide substrate has been obtained. The molecular chaperone activity and conformational switch are functionally linked with ATP hydrolysis. A high-resolution structure of the ATPase domain is required to provide an understanding of the mechanism of ATP hydrolysis and how it affects communication between C- and N-terminal domains. The crystal structure of the human Hsp70 ATPase domain (hATPase) has been determined and refined at 1. 84 A, using synchrotron radiation at 120K. Two calcium sites were identified: the first calcium binds within the catalytic pocket, bridging ADP and inorganic phosphate, and the second calcium is tightly coordinated on the protein surface by Glu231, Asp232 and the carbonyl of His227. Overall, the structure of hATPase is similar to bATPase. Differences between them are found in the loops, the sites of amino acid substitution and the calcium-binding sites. Human Hsp70 chaperone is phosphorylated in vitro in the presence of divalent ions, calcium being the most effective. The structural similarity of hATPase and bATPase and the sequence similarity within the Hsp70 chaperone family suggest a universal mechanism of ATP hydrolysis among all Hsp70 molecular chaperones. Two calcium ions have been found in the hATPase structure. One corresponds to the magnesium site in bATPase and appears to be important for ATP hydrolysis and in vitro phosphorylation. Local changes

  10. Characterization of Novel Calmodulin Binding Domains within IQ Motifs of IQGAP1

    PubMed Central

    Jang, Deok-Jin; Ban, Byungkwan; Lee, Jin-A

    2011-01-01

    IQ motif-containing GTPase-activating protein 1 (IQGAP1), which is a well-known calmodulin (CaM) binding protein, is involved in a wide range of cellular processes including cell proliferation, tumorigenesis, adhesion, and migration. Interaction of IQGAP1 with CaM is important for its cellular functions. Although each IQ domain of IQGAP1 for CaM binding has been characterized in a Ca2+-dependent or -independent manner, it was not clear which IQ motifs are physiologically relevant for CaM binding in the cells. In this study, we performed immunoprecipitation using 3xFLAGhCaM in mammalian cell lines to characterize the domains of IQGAP1 that are key for CaM binding under physiological conditions. Interestingly, using this method, we identified two novel domains, IQ(2.7-3) and IQ(3.5-4.4), within IQGAP1 that were involved in Ca2+-independent or -dependent CaM binding, respectively. Mutant analysis clearly showed that the hydrophobic regions within IQ(2.7-3) were mainly involved in apoCaM binding, while the basic amino acids and hydrophobic region of IQ(3.5-4.4) were required for Ca2+/CaM binding. Finally, we showed that IQ(2.7-3) was the main apoCaM binding domain and both IQ(2.7-3) and IQ(3.5-4.4) were required for Ca2+/CaM binding within IQ(1- 2-3-4). Thus, we identified and characterized novel direct CaM binding motifs essential for IQGAP1. This finding indicates that IQGAP1 plays a dynamic role via direct interactions with CaM in a Ca2+-dependent or -independent manner. PMID:22080369

  11. The identification of FANCD2 DNA binding domains reveals nuclear localization sequences.

    PubMed

    Niraj, Joshi; Caron, Marie-Christine; Drapeau, Karine; Bérubé, Stéphanie; Guitton-Sert, Laure; Coulombe, Yan; Couturier, Anthony M; Masson, Jean-Yves

    2017-08-21

    Fanconi anemia (FA) is a recessive genetic disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. The FA pathway consists of at least 21 FANC genes (FANCA-FANCV), and the encoded protein products interact in a common cellular pathway to gain resistance against DNA interstrand crosslinks. After DNA damage, FANCD2 is monoubiquitinated and accumulates on chromatin. FANCD2 plays a central role in the FA pathway, using yet unidentified DNA binding regions. By using synthetic peptide mapping and DNA binding screen by electromobility shift assays, we found that FANCD2 bears two major DNA binding domains predominantly consisting of evolutionary conserved lysine residues. Furthermore, one domain at the N-terminus of FANCD2 bears also nuclear localization sequences for the protein. Mutations in the bifunctional DNA binding/NLS domain lead to a reduction in FANCD2 monoubiquitination and increase in mitomycin C sensitivity. Such phenotypes are not fully rescued by fusion with an heterologous NLS, which enable separation of DNA binding and nuclear import functions within this domain that are necessary for FANCD2 functions. Collectively, our results enlighten the importance of DNA binding and NLS residues in FANCD2 to activate an efficient FA pathway. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Spinmotive force due to domain wall motion in high field regime

    NASA Astrophysics Data System (ADS)

    Ieda, Jun'ichi; Yamane, Yuta; Maekawa, Sadamichi

    2012-02-01

    Spinmotive force associated with a moving vortex domain wall is investigated numerically. Dynamics of magnetization textures such as a domain wall exerts a non-conservative spin-force on conduction electrons [1], offering a new concept of magnetic devices [2]. This spinmotive force in permalloy nanowires has been detected by voltage measurement [3] where magnitude of the signal is limited less than 500 nV. Theoretically it is suggested that the spinmotive force signal increases as a function of external magnetic fields. At higher magnetic fields, however, the wall propagation mode becomes rather chaotic involving transformations of the wall structure and it remains to be seen how the spinmotive force appears. Numerical simulations show that the spinmotive force scales with the field even in a field range where the wall motion is no longer associated coherent precession. This feature has been tested in a recent experiment [4]. Further enhancement of the spinmotive force is explored by designing ferromagnetic nanostructures [5] and materials. [1] S. Barnes and S. Maekawa, PRL (2007). [2] S. Barnes, J. Ieda, and S. Maekawa, APL (2006). [3] S. A. Yang et al., PRL (2009). [4] M. Hayashi, J. Ieda et al., submitted. [5] Y. Yamane, J. Ieda et al., APEX (2011).

  13. Current-induced instability of domain walls in cylindrical nanowires

    NASA Astrophysics Data System (ADS)

    Wang, Weiwei; Zhang, Zhaoyang; Pepper, Ryan A.; Mu, Congpu; Zhou, Yan; Fangohr, Hans

    2018-01-01

    We study the current-driven domain wall (DW) motion in cylindrical nanowires using micromagnetic simulations by implementing the Landau-Lifshitz-Gilbert equation with nonlocal spin-transfer torque in a finite difference micromagnetic package. We find that in the presence of DW, Gaussian wave packets (spin waves) will be generated when the charge current is suddenly applied to the system. This effect is excluded when using the local spin-transfer torque. The existence of spin waves emission indicates that transverse domain walls can not move arbitrarily fast in cylindrical nanowires although they are free from the Walker limit. We establish an upper velocity limit for DW motion by analyzing the stability of Gaussian wave packets using the local spin-transfer torque. Micromagnetic simulations show that the stable region obtained by using nonlocal spin-transfer torque is smaller than that by using its local counterpart. This limitation is essential for multiple DWs since the instability of Gaussian wave packets will break the structure of multiple DWs.

  14. A novel type of peptidoglycan-binding domain highly specific for amidated D-Asp cross-bridge, identified in Lactobacillus casei bacteriophage endolysins.

    PubMed

    Regulski, Krzysztof; Courtin, Pascal; Kulakauskas, Saulius; Chapot-Chartier, Marie-Pierre

    2013-07-12

    Peptidoglycan hydrolases (PGHs) are responsible for bacterial cell lysis. Most PGHs have a modular structure comprising a catalytic domain and a cell wall-binding domain (CWBD). PGHs of bacteriophage origin, called endolysins, are involved in bacterial lysis at the end of the infection cycle. We have characterized two endolysins, Lc-Lys and Lc-Lys-2, identified in prophages present in the genome of Lactobacillus casei BL23. These two enzymes have different catalytic domains but similar putative C-terminal CWBDs. By analyzing purified peptidoglycan (PG) degradation products, we showed that Lc-Lys is an N-acetylmuramoyl-L-alanine amidase, whereas Lc-Lys-2 is a γ-D-glutamyl-L-lysyl endopeptidase. Remarkably, both lysins were able to lyse only Gram-positive bacterial strains that possess PG with D-Ala(4)→D-Asx-L-Lys(3) in their cross-bridge, such as Lactococcus casei, Lactococcus lactis, and Enterococcus faecium. By testing a panel of L. lactis cell wall mutants, we observed that Lc-Lys and Lc-Lys-2 were not able to lyse mutants with a modified PG cross-bridge, constituting D-Ala(4)→L-Ala-(L-Ala/L-Ser)-L-Lys(3); moreover, they do not lyse the L. lactis mutant containing only the nonamidated D-Asp cross-bridge, i.e. D-Ala(4)→D-Asp-L-Lys(3). In contrast, Lc-Lys could lyse the ampicillin-resistant E. faecium mutant with 3→3 L-Lys(3)-D-Asn-L-Lys(3) bridges replacing the wild-type 4→3 D-Ala(4)-D-Asn-L-Lys(3) bridges. We showed that the C-terminal CWBD of Lc-Lys binds PG containing mainly D-Asn but not PG with only the nonamidated D-Asp-containing cross-bridge, indicating that the CWBD confers to Lc-Lys its narrow specificity. In conclusion, the CWBD characterized in this study is a novel type of PG-binding domain targeting specifically the D-Asn interpeptide bridge of PG.

  15. Temperature dependence of the domain wall magneto-Seebeck effect: avoiding artifacts of lead contributions

    NASA Astrophysics Data System (ADS)

    Fernández Scarioni, Alexander; Krzysteczko, Patryk; Sievers, Sibylle; Hu, Xiukun; Schumacher, Hans W.

    2018-06-01

    We study the resistive and thermopower signatures of a single domain wall in a magnetic nanowire in the temperature range from 4 K to 204 K. The results are compared to the anisotropic magnetoresistance (AMR) and anisotropic magneto-Seebeck (AMS) data of the whole permalloy nanowire. The AMS ratio of the nanowire reveals a sign change at a temperature of 98 K, while the AMR ratio is positive over the complete temperature range. This behavior is also observed for the domain wall, allowing an attribution of the measured signatures to the domain wall magneto-Seebeck and domain wall magnetoresistive contributions. However, the observed zero crossing of the AMS ratio, in both types of measurements is not expected for permalloy, since the Mott formula predicts a temperature dependency of the AMS identical to the AMR. We discuss the origin of this behavior and can attribute it to the contributions of the lead and the protective platinum layer used in our devices. A correction scheme is presented and applied. Such contributions could also play a role in the analysis of magneto-Seebeck effects in other nanoscale devices, such as the tunnel magneto-Seebeck effect of magnetic tunnel junctions.

  16. Domain Wall Evolution in Phase Transforming Oxides

    DTIC Science & Technology

    2015-01-14

    configumtions under driving forces (e.g. changes in temperature and electric fields) in an effort to: 1) understand the underlying linkage between -1...configurations under driving forces (e.g. changes in temperature and electric fields) in an effort to: 1) understand the underlying linkage between...Extensive domain wall motion and deaging resistance in morphotropic 0.55Bi(Ni1/2Ti1/2)O3–0.45PbTiO3 polycrystalline ferroelectrics, Applied Physics Letters

  17. Functional Dynamics of PDZ Binding Domains: A Normal-Mode Analysis

    PubMed Central

    De Los Rios, Paolo; Cecconi, Fabio; Pretre, Anna; Dietler, Giovanni; Michielin, Olivier; Piazza, Francesco; Juanico, Brice

    2005-01-01

    Postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains are relatively small (80–120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible for communication between distant regions of the protein, in agreement with recent NMR experiments. Thus, PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbinding events. PMID:15821164

  18. RNA-binding properties and mapping of the RNA-binding domain from the movement protein of Prunus necrotic ringspot virus.

    PubMed

    Herranz, M Carmen; Pallás, Vicente

    2004-03-01

    The movement protein (MP) of Prunus necrotic ringspot virus (PNRSV) is involved in intercellular virus transport. In this study, putative RNA-binding properties of the PNRSV MP were studied. The PNRSV MP was produced in Escherichia coli using an expression vector. Electrophoretic mobility shift assays (EMSAs) using DIG-labelled riboprobes demonstrated that PNRSV MP bound ssRNA cooperatively without sequence specificity. Two different ribonucleoprotein complexes were found to be formed depending on the molar MP : PNRSV RNA ratio. The different responses of the complexes to urea treatment strongly suggested that they have different structural properties. Deletion mutagenesis followed by Northwestern analysis allowed location of a nucleic acid binding domain to aa 56-88. This 33 aa RNA-binding motif is the smallest region delineated among members of the family Bromoviridae for which RNA-binding properties have been demonstrated. This domain is highly conserved within all phylogenetic subgroups previously described for PNRSV isolates. Interestingly, the RNA-binding domain described here and the one described for Alfamovirus are located at the N terminus of their corresponding MPs, whereas similar domains previously characterized in members of the genera Bromovirus and Cucumovirus are present at the C terminus, strongly reflecting their corresponding phylogenetic relationships. The evolutionary implications of this observation are discussed.

  19. ATP Binding to p97/VCP D1 Domain Regulates Selective Recruitment of Adaptors to Its Proximal N-Domain

    PubMed Central

    Chia, Wei Sheng; Chia, Diana Xueqi; Rao, Feng; Bar Nun, Shoshana; Geifman Shochat, Susana

    2012-01-01

    p97/Valosin-containing protein (VCP) is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD). It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell. PMID:23226521

  20. ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

    PubMed

    Chia, Wei Sheng; Chia, Diana Xueqi; Rao, Feng; Bar Nun, Shoshana; Geifman Shochat, Susana

    2012-01-01

    p97/Valosin-containing protein (VCP) is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD). It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

  1. Crystal structures of the transpeptidase domain of the Mycobacterium tuberculosis penicillin-binding protein PonA1 reveal potential mechanisms of antibiotic resistance.

    PubMed

    Filippova, Ekaterina V; Kieser, Karen J; Luan, Chi-Hao; Wawrzak, Zdzislaw; Kiryukhina, Olga; Rubin, Eric J; Anderson, Wayne F

    2016-06-01

    Mycobacterium tuberculosis is a human respiratory pathogen that causes the deadly disease tuberculosis. The rapid global spread of antibiotic-resistant M. tuberculosis makes tuberculosis infections difficult to treat. To overcome this problem new effective antimicrobial strategies are urgently needed. One promising target for new therapeutic approaches is PonA1, a class A penicillin-binding protein, which is required for maintaining physiological cell wall synthesis and cell shape during growth in mycobacteria. Here, crystal structures of the transpeptidase domain, the enzymatic domain responsible for penicillin binding, of PonA1 from M. tuberculosis in the inhibitor-free form and in complex with penicillin V are reported. We used site-directed mutagenesis, antibiotic profiling experiments, and fluorescence thermal shift assays to measure PonA1's sensitivity to different classes of β-lactams. Structural comparison of the PonA1 apo-form and the antibiotic-bound form shows that binding of penicillin V induces conformational changes in the position of the loop β4'-α3 surrounding the penicillin-binding site. We have also found that binding of different antibiotics including penicillin V positively impacts protein stability, while other tested β-lactams such as clavulanate or meropenem resulted in destabilization of PonA1. Our antibiotic profiling experiments indicate that the transpeptidase activity of PonA1 in both M. tuberculosis and M. smegmatis mediates tolerance to specific cell wall-targeting antibiotics, particularly to penicillin V and meropenem. Because M. tuberculosis is an important human pathogen, these structural data provide a template to design novel transpeptidase inhibitors to treat tuberculosis infections. Structural data are available in the PDB database under the accession numbers 5CRF and 5CXW. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  2. Calcium binding to calmodulin mutants monitored by domain-specific intrinsic phenylalanine and tyrosine fluorescence.

    PubMed Central

    VanScyoc, Wendy S; Sorensen, Brenda R; Rusinova, Elena; Laws, William R; Ross, J B Alexander; Shea, Madeline A

    2002-01-01

    Cooperative calcium binding to the two homologous domains of calmodulin (CaM) induces conformational changes that regulate its association with and activation of numerous cellular target proteins. Calcium binding to the pair of high-affinity sites (III and IV in the C-domain) can be monitored by observing calcium-dependent changes in intrinsic tyrosine fluorescence intensity (lambda(ex)/lambda(em) of 277/320 nm). However, calcium binding to the low-affinity sites (I and II in the N-domain) is more difficult to measure with optical spectroscopy because that domain of CaM does not contain tryptophan or tyrosine. We recently demonstrated that calcium-dependent changes in intrinsic phenylalanine fluorescence (lambda(ex)/lambda(em) of 250/280 nm) of an N-domain fragment of CaM reflect occupancy of sites I and II (VanScyoc, W. S., and M. A. Shea, 2001, Protein Sci. 10:1758-1768). Using steady-state and time-resolved fluorescence methods, we now show that these excitation and emission wavelength pairs for phenylalanine and tyrosine fluorescence can be used to monitor equilibrium calcium titrations of the individual domains in full-length CaM. Calcium-dependent changes in phenylalanine fluorescence specifically indicate ion occupancy of sites I and II in the N-domain because phenylalanine residues in the C-domain are nonemissive. Tyrosine emission from the C-domain does not interfere with phenylalanine fluorescence signals from the N-domain. This is the first demonstration that intrinsic fluorescence may be used to monitor calcium binding to each domain of CaM. In this way, we also evaluated how mutations of two residues (Arg74 and Arg90) located between sites II and III can alter the calcium-binding properties of each of the domains. The mutation R74A caused an increase in the calcium affinity of sites I and II in the N-domain. The mutation R90A caused an increase in calcium affinity of sites III and IV in the C-domain whereas R90G caused an increase in calcium affinity

  3. Determination of domain wall chirality using in situ Lorentz transmission electron microscopy

    DOE PAGES

    Chess, Jordan J.; Montoya, Sergio A.; Fullerton, Eric E.; ...

    2017-02-23

    Controlling domain wall chirality is increasingly seen in non-centrosymmetric materials. Mapping chiral magnetic domains requires knowledge about all the vector components of the magnetization, which poses a problem for conventional Lorentz transmission electron microscopy (LTEM) that is only sensitive to magnetic fields perpendicular to the electron beams direction of travel. The standard approach in LTEM for determining the third component of the magnetization is to tilt the sample to some angle and record a second image. Furthermore, this presents a problem for any domain structures that are stabilized by an applied external magnetic field (e.g. skyrmions), because the standard LTEMmore » setup does not allow independent control of the angle of an applied magnetic field, and sample tilt angle. Here we show that applying a modified transport of intensity equation analysis to LTEM images collected during an applied field sweep, we can determine the domain wall chirality of labyrinth domains in a perpendicularly magnetized material, avoiding the need to tilt the sample.« less

  4. Determination of domain wall chirality using in situ Lorentz transmission electron microscopy

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

    Chess, Jordan J.; Montoya, Sergio A.; Fullerton, Eric E.

    Controlling domain wall chirality is increasingly seen in non-centrosymmetric materials. Mapping chiral magnetic domains requires knowledge about all the vector components of the magnetization, which poses a problem for conventional Lorentz transmission electron microscopy (LTEM) that is only sensitive to magnetic fields perpendicular to the electron beams direction of travel. The standard approach in LTEM for determining the third component of the magnetization is to tilt the sample to some angle and record a second image. Furthermore, this presents a problem for any domain structures that are stabilized by an applied external magnetic field (e.g. skyrmions), because the standard LTEMmore » setup does not allow independent control of the angle of an applied magnetic field, and sample tilt angle. Here we show that applying a modified transport of intensity equation analysis to LTEM images collected during an applied field sweep, we can determine the domain wall chirality of labyrinth domains in a perpendicularly magnetized material, avoiding the need to tilt the sample.« less

  5. Cross-talk between the ligand- and DNA-binding domains of estrogen receptor.

    PubMed

    Huang, Wei; Greene, Geoffrey L; Ravikumar, Krishnakumar M; Yang, Sichun

    2013-11-01

    Estrogen receptor alpha (ERα) is a hormone-responsive transcription factor that contains several discrete functional domains, including a ligand-binding domain (LBD) and a DNA-binding domain (DBD). Despite a wealth of knowledge about the behaviors of individual domains, the molecular mechanisms of cross-talk between LBD and DBD during signal transduction from hormone to DNA-binding of ERα remain elusive. Here, we apply a multiscale approach combining coarse-grained (CG) and atomistically detailed simulations to characterize this cross-talk mechanism via an investigation of the ERα conformational landscape. First, a CG model of ERα is built based on crystal structures of individual LBDs and DBDs, with more emphasis on their interdomain interactions. Second, molecular dynamics simulations are implemented and enhanced sampling is achieved via the "push-pull-release" strategy in the search for different LBD-DBD orientations. Third, multiple energetically stable ERα conformations are identified on the landscape. A key finding is that estradiol-bound LBDs utilize the well-described activation helix H12 to pack and stabilize LBD-DBD interactions. Our results suggest that the estradiol-bound LBDs can serve as a scaffold to position and stabilize the DBD-DNA complex, consistent with experimental observations of enhanced DNA binding with the LBD. Final assessment using atomic-level simulations shows that these CG-predicted models are significantly stable within a 15-ns simulation window and that specific pairs of lysine residues in close proximity at the domain interfaces could serve as candidate sites for chemical cross-linking studies. Together, these simulation results provide a molecular view of the role of ERα domain interactions in response to hormone binding. Copyright © 2013 Wiley Periodicals, Inc.

  6. Zinc-binding Domain of the Bacteriophage T7 DNA Primase Modulates Binding to the DNA Template*

    PubMed Central

    Lee, Seung-Joo; Zhu, Bin; Akabayov, Barak; Richardson, Charles C.

    2012-01-01

    The zinc-binding domain (ZBD) of prokaryotic DNA primases has been postulated to be crucial for recognition of specific sequences in the single-stranded DNA template. To determine the molecular basis for this role in recognition, we carried out homolog-scanning mutagenesis of the zinc-binding domain of DNA primase of bacteriophage T7 using a bacterial homolog from Geobacillus stearothermophilus. The ability of T7 DNA primase to catalyze template-directed oligoribonucleotide synthesis is eliminated by substitution of any five-amino acid residue-long segment within the ZBD. The most significant defect occurs upon substitution of a region (Pro-16 to Cys-20) spanning two cysteines that coordinate the zinc ion. The role of this region in primase function was further investigated by generating a protein library composed of multiple amino acid substitutions for Pro-16, Asp-18, and Asn-19 followed by genetic screening for functional proteins. Examination of proteins selected from the screening reveals no change in sequence-specific recognition. However, the more positively charged residues in the region facilitate DNA binding, leading to more efficient oligoribonucleotide synthesis on short templates. The results suggest that the zinc-binding mode alone is not responsible for sequence recognition, but rather its interaction with the RNA polymerase domain is critical for DNA binding and for sequence recognition. Consequently, any alteration in the ZBD that disturbs its conformation leads to loss of DNA-dependent oligoribonucleotide synthesis. PMID:23024359

  7. Simultaneous prediction of binding free energy and specificity for PDZ domain-peptide interactions

    NASA Astrophysics Data System (ADS)

    Crivelli, Joseph J.; Lemmon, Gordon; Kaufmann, Kristian W.; Meiler, Jens

    2013-12-01

    Interactions between protein domains and linear peptides underlie many biological processes. Among these interactions, the recognition of C-terminal peptides by PDZ domains is one of the most ubiquitous. In this work, we present a mathematical model for PDZ domain-peptide interactions capable of predicting both affinity and specificity of binding based on X-ray crystal structures and comparative modeling with R osetta. We developed our mathematical model using a large phage display dataset describing binding specificity for a wild type PDZ domain and 91 single mutants, as well as binding affinity data for a wild type PDZ domain binding to 28 different peptides. Structural refinement was carried out through several R osetta protocols, the most accurate of which included flexible peptide docking and several iterations of side chain repacking and backbone minimization. Our findings emphasize the importance of backbone flexibility and the energetic contributions of side chain-side chain hydrogen bonds in accurately predicting interactions. We also determined that predicting PDZ domain-peptide interactions became increasingly challenging as the length of the peptide increased in the N-terminal direction. In the training dataset, predicted binding energies correlated with those derived through calorimetry and specificity switches introduced through single mutations at interface positions were recapitulated. In independent tests, our best performing protocol was capable of predicting dissociation constants well within one order of magnitude of the experimental values and specificity profiles at the level of accuracy of previous studies. To our knowledge, this approach represents the first integrated protocol for predicting both affinity and specificity for PDZ domain-peptide interactions.

  8. Segmental front line dynamics of randomly pinned ferroelastic domain walls

    NASA Astrophysics Data System (ADS)

    Puchberger, S.; Soprunyuk, V.; Schranz, W.; Carpenter, M. A.

    2018-01-01

    Dynamic mechanical analysis (DMA) measurements as a function of temperature, frequency, and dynamic force amplitude are used to perform a detailed study of the domain wall motion in LaAlO3. In previous DMA measurements Harrison et al. [Phys. Rev. B 69, 144101 (2004), 10.1103/PhysRevB.69.144101] found evidence for dynamic phase transitions of ferroelastic domain walls in LaAlO3. In the present work we focus on the creep-to-relaxation region of domain wall motion using two complementary methods. We determine, in addition to dynamic susceptibility data, waiting time distributions of strain jerks during slowly increasing stress. These strain jerks, which result from self-similar avalanches close to the depinning threshold, follow a power-law behavior with an energy exponent ɛ =1.7 ±0.1 . Also, the distribution of waiting times between events follows a power law N (tw) ∝tw-(n +1 ) with an exponent n =0.9 , which transforms to a power law of susceptibility S (ω ) ∝ω-n . The present dynamic susceptibility data can be well fitted with a power law, with the same exponent (n =0.9 ) up to a characteristic frequency ω ≈ω* , where a crossover from stochastic DW motion to the pinned regime is well described using the scaling function of Fedorenko et al. [Phys. Rev. B 70, 224104 (2004), 10.1103/PhysRevB.70.224104].

  9. Molecular mechanism of membrane binding of the GRP1 PH domain.

    PubMed

    Lai, Chun-Liang; Srivastava, Anand; Pilling, Carissa; Chase, Anna R; Falke, Joseph J; Voth, Gregory A

    2013-09-09

    The pleckstrin homology (PH) domain of the general receptor of phosphoinositides 1 (GRP1) protein selectively binds to a rare signaling phospholipid, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), in the membrane. The specific PIP3 lipid docking of GRP1 PH domain is essential to protein cellular function and is believed to occur in a stepwise process, electrostatic-driven membrane association followed by the specific PIP3 binding. By a combination of all-atom molecular dynamics (MD) simulations, coarse-grained analysis, electron paramagnetic resonance (EPR) membrane docking geometry, and fluorescence resonance energy transfer (FRET) kinetic studies, we have investigated the search and bind process in the GRP1 PH domain at the molecular scale. We simulated the two membrane binding states of the GRP1 PH domain in the PIP3 search process, before and after the GRP1 PH domain docks with the PIP3 lipid. Our results suggest that the background anionic phosphatidylserine lipids, which constitute around one-fifth of the membrane by composition, play a critical role in the initial stages of recruiting protein to the membrane surface through non-specific electrostatic interactions. Our data also reveal a previously unseen transient membrane association mechanism that is proposed to enable a two-dimensional "hopping" search of the membrane surface for the rare PIP3 target lipid. We further modeled the PIP3-bound membrane-protein system using the EPR membrane docking structure for the MD simulations, quantitatively validating the EPR membrane docking structure and augmenting our understanding of the binding interface with atomic-level detail. Several observations and hypotheses reached from our MD simulations are also supported by experimental kinetic studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Enhancement of exchange bias in ferromagnetic/antiferromagnetic core-shell nanoparticles through ferromagnetic domain wall formation

    NASA Astrophysics Data System (ADS)

    Wu, Rui; Ding, Shilei; Lai, Youfang; Tian, Guang; Yang, Jinbo

    2018-01-01

    The spin configuration in the ferromagnetic part during the magnetization reversal plays a crucial role in the exchange bias effect. Through Monte Carlo simulation, the exchange bias effect in ferromagnetic-antiferromagnetic core-shell nanoparticles is investigated. Magnetization reversals in the ferromagnetic core were controlled between the coherent rotation and the domain wall motion by modulating the ferromagnetic domain wall width with parameters of uniaxial anisotropy constant and exchange coupling strength. An anomalous monotonic dependence of exchange bias on the uniaxial anisotropy constant is found in systems with small exchange coupling, showing an obvious violation of classic Meiklejohn-Bean model, while domain walls are found to form close to the interface and propagate in the ferromagnetic core with larger uniaxial anisotropy in both branches of the hysteresis. The asymmetric magnetization reversal with the formation of a spherical domain wall dramatically reduces the coercive field in the ascending branch, leading to the enhancement of the exchange bias. The results provide another degree of freedom to optimize the magnetic properties of magnetic nanoparticles for applications.

  11. An exact solution for a thick domain wall in general relativity

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Noetzold, Dirk

    1989-01-01

    An exact solution of the Einstein equations for a static, planar domain wall with finite thickness is presented. At infinity, density and pressure vanish and the space-time tends to the Minkowski vacuum on one side of the wall and to the Taub vacuum on the other side. A surprising feature of this solution is that the density and pressure distribution are symmetric about the central plane of the wall whereas the space-time metric and therefore also the gravitational field experienced by a test particle is asymmetric.

  12. Logic and memory concepts for all-magnetic computing based on transverse domain walls

    NASA Astrophysics Data System (ADS)

    Vandermeulen, J.; Van de Wiele, B.; Dupré, L.; Van Waeyenberge, B.

    2015-06-01

    We introduce a non-volatile digital logic and memory concept in which the binary data is stored in the transverse magnetic domain walls present in in-plane magnetized nanowires with sufficiently small cross sectional dimensions. We assign the digital bit to the two possible orientations of the transverse domain wall. Numerical proofs-of-concept are presented for a NOT-, AND- and OR-gate, a FAN-out as well as a reading and writing device. Contrary to the chirality based vortex domain wall logic gates introduced in Omari and Hayward (2014 Phys. Rev. Appl. 2 044001), the presented concepts remain applicable when miniaturized and are driven by electrical currents, making the technology compatible with the in-plane racetrack memory concept. The individual devices can be easily combined to logic networks working with clock speeds that scale linearly with decreasing design dimensions. This opens opportunities to an all-magnetic computing technology where the digital data is stored and processed under the same magnetic representation.

  13. Multivalent binding of formin-binding protein 21 (FBP21)-tandem-WW domains fosters protein recognition in the pre-spliceosome.

    PubMed

    Klippel, Stefan; Wieczorek, Marek; Schümann, Michael; Krause, Eberhard; Marg, Berenice; Seidel, Thorsten; Meyer, Tim; Knapp, Ernst-Walter; Freund, Christian

    2011-11-04

    The high abundance of repetitive but nonidentical proline-rich sequences in spliceosomal proteins raises the question of how these known interaction motifs recruit their interacting protein domains. Whereas complex formation of these adaptors with individual motifs has been studied in great detail, little is known about the binding mode of domains arranged in tandem repeats and long proline-rich sequences including multiple motifs. Here we studied the interaction of the two adjacent WW domains of spliceosomal protein FBP21 with several ligands of different lengths and composition to elucidate the hallmarks of multivalent binding for this class of recognition domains. First, we show that many of the proteins that define the cellular proteome interacting with FBP21-WW1-WW2 contain multiple proline-rich motifs. Among these is the newly identified binding partner SF3B4. Fluorescence resonance energy transfer (FRET) analysis reveals the tandem-WW domains of FBP21 to interact with splicing factor 3B4 (SF3B4) in nuclear speckles where splicing takes place. Isothermal titration calorimetry and NMR shows that the tandem arrangement of WW domains and the multivalency of the proline-rich ligands both contribute to affinity enhancement. However, ligand exchange remains fast compared with the NMR time scale. Surprisingly, a N-terminal spin label attached to a bivalent ligand induces NMR line broadening of signals corresponding to both WW domains of the FBP21-WW1-WW2 protein. This suggests that distinct orientations of the ligand contribute to a delocalized and semispecific binding mode that should facilitate search processes within the spliceosome.

  14. Biological effects of individually synthesized TNF-binding domain of variola virus CrmB protein.

    PubMed

    Tsyrendorzhiev, D D; Orlovskaya, I A; Sennikov, S V; Tregubchak, T V; Gileva, I P; Tsyrendorzhieva, M D; Shchelkunov, S N

    2014-06-01

    The biological characteristics of a 17-kDa protein synthesized in bacterial cells, a TNF-binding domain (VARV-TNF-BP) of a 47-kDa variola virus CrmB protein (VARV-CrmB) consisting of TNF-binding and chemokine-binding domains, were studied. Removal of the C-terminal chemokine-binding domain from VARV-CrmB protein was inessential for the efficiency of its inhibition of TNF cytotoxicity towards L929 mouse fibroblast culture and for TNF-induced oxidative metabolic activity of mouse blood leukocytes. The results of this study could form the basis for further studies of VARV-TNF-BP mechanisms of activity for prospective use in practical medicine.

  15. Characterization of substrate binding of the WW domains in human WWP2 protein.

    PubMed

    Jiang, Jiahong; Wang, Nan; Jiang, Yafei; Tan, Hongwei; Zheng, Jimin; Chen, Guangju; Jia, Zongchao

    2015-07-08

    WW domains harbor substrates containing proline-rich motifs, but the substrate specificity and binding mechanism remain elusive for those WW domains less amenable for structural studies, such as human WWP2 (hWWP2). Herein we have employed multiple techniques to investigate the second WW domain (WW2) in hWWP2. Our results show that hWWP2 is a specialized E3 for PPxY motif-containing substrates only and does not recognize other amino acids and phospho-residues. The strongest binding affinity of WW2, and the incompatibility between each WW domain, imply a novel relationship, and our SPR experiment reveals a dynamic binding mode in Class-I WW domains for the first time. The results from alanine-scanning mutagenesis and modeling further point to functionally conserved residues in WW2. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  16. Fast and reliable prediction of domain-peptide binding affinity using coarse-grained structure models.

    PubMed

    Tian, Feifei; Tan, Rui; Guo, Tailin; Zhou, Peng; Yang, Li

    2013-07-01

    Domain-peptide recognition and interaction are fundamentally important for eukaryotic signaling and regulatory networks. It is thus essential to quantitatively infer the binding stability and specificity of such interaction based upon large-scale but low-accurate complex structure models which could be readily obtained from sophisticated molecular modeling procedure. In the present study, a new method is described for the fast and reliable prediction of domain-peptide binding affinity with coarse-grained structure models. This method is designed to tolerate strong random noises involved in domain-peptide complex structures and uses statistical modeling approach to eliminate systematic bias associated with a group of investigated samples. As a paradigm, this method was employed to model and predict the binding behavior of various peptides to four evolutionarily unrelated peptide-recognition domains (PRDs), i.e. human amph SH3, human nherf PDZ, yeast syh GYF and yeast bmh 14-3-3, and moreover, we explored the molecular mechanism and biological implication underlying the binding of cognate and noncognate peptide ligands to their domain receptors. It is expected that the newly proposed method could be further used to perform genome-wide inference of domain-peptide binding at three-dimensional structure level. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Probing the electrostatics and pharmacologic modulation of sequence-specific binding by the DNA-binding domain of the ETS-family transcription factor PU.1: a binding affinity and kinetics investigation

    PubMed Central

    Munde, Manoj; Poon, Gregory M. K.; Wilson, W. David

    2013-01-01

    Members of the ETS family of transcription factors regulate a functionally diverse array of genes. All ETS proteins share a structurally-conserved but sequence-divergent DNA-binding domain, known as the ETS domain. Although the structure and thermodynamics of the ETS-DNA complexes are well known, little is known about the kinetics of sequence recognition, a facet that offers potential insight into its molecular mechanism. We have characterized DNA binding by the ETS domain of PU.1 by biosensor-surface plasmon resonance (SPR). SPR analysis revealed a striking kinetic profile for DNA binding by the PU.1 ETS domain. At low salt concentrations, it binds high-affinity cognate DNA with a very slow association rate constant (≤105 M−1 s−1), compensated by a correspondingly small dissociation rate constant. The kinetics are strongly salt-dependent but mutually balance to produce a relatively weak dependence in the equilibrium constant. This profile contrasts sharply with reported data for other ETS domains (e.g., Ets-1, TEL) for which high-affinity binding is driven by rapid association (>107 M−1 s−1). We interpret this difference in terms of the hydration properties of ETS-DNA binding and propose that at least two mechanisms of sequence recognition are employed by this family of DNA-binding domain. Additionally, we use SPR to demonstrate the potential for pharmacological inhibition of sequence-specific ETS-DNA binding, using the minor groove-binding distamycin as a model compound. Our work establishes SPR as a valuable technique for extending our understanding of the molecular mechanisms of ETS-DNA interactions as well as developing potential small-molecule agents for biotechnological and therapeutic purposes. PMID:23416556

  18. Presence of an SH2 domain in the actin-binding protein tensin.

    PubMed

    Davis, S; Lu, M L; Lo, S H; Lin, S; Butler, J A; Druker, B J; Roberts, T M; An, Q; Chen, L B

    1991-05-03

    The molecular cloning of the complementary DNA coding for a 90-kilodalton fragment of tensin, an actin-binding component of focal contacts and other submembraneous cytoskeletal structures, is reported. The derived amino acid sequence revealed the presence of a Src homology 2 (SH2) domain. This domain is shared by a number of signal transduction proteins including nonreceptor tyrosine kinases such as Abl, Fps, Src, and Src family members, the transforming protein Crk, phospholipase C-gamma 1, PI-3 (phosphatidylinositol) kinase, and guanosine triphosphatase-activating protein (GAP). Like the SH2 domain found in Src, Crk, and Abl, the SH2 domain of tensin bound specifically to a number of phosphotyrosine-containing proteins from v-src-transformed cells. Tensin was also found to be phosphorylated on tyrosine residues. These findings suggest that by possessing both actin-binding and phosphotyrosine-binding activities and being itself a target for tyrosine kinases, tensin may link signal transduction pathways with the cytoskeleton.

  19. Distinct mechanisms of a phosphotyrosyl peptide binding to two SH2 domains.

    PubMed

    Pang, Xiaodong; Zhou, Huan-Xiang

    2014-05-01

    Protein phosphorylation is very common post-translational modification, catalyzed by kinases, for signaling and regulation. Phosphotyrosines frequently target SH2 domains. The spleen tyrosine kinase (Syk) is critical for tyrosine phosphorylation of multiple proteins and for regulation of important pathways. Phosphorylation of both Y342 and Y346 in Syk linker B is required for optimal signaling. The SH2 domains of Vav1 and PLC-γ both bind this doubly phosphorylated motif. Here we used a recently developed method to calculate the effects of Y342 and Y346 phosphorylation on the rate constants of a peptide from Syk linker B binding to the SH2 domains of Vav1 and PLC-γ. The predicted effects agree well with experimental observations. Moreover, we found that the same doubly phosphorylated peptide binds the two SH2 domains via distinct mechanisms, with apparent rigid docking for Vav1 SH2 and dock-and-coalesce for PLC-γ SH2.

  20. Magnetic domain wall engineering in a nanoscale permalloy junction

    NASA Astrophysics Data System (ADS)

    Wang, Junlin; Zhang, Xichao; Lu, Xianyang; Zhang, Jason; Yan, Yu; Ling, Hua; Wu, Jing; Zhou, Yan; Xu, Yongbing

    2017-08-01

    Nanoscale magnetic junctions provide a useful approach to act as building blocks for magnetoresistive random access memories (MRAM), where one of the key issues is to control the magnetic domain configuration. Here, we study the domain structure and the magnetic switching in the Permalloy (Fe20Ni80) nanoscale magnetic junctions with different thicknesses by using micromagnetic simulations. It is found that both the 90-° and 45-° domain walls can be formed between the junctions and the wire arms depending on the thickness of the device. The magnetic switching fields show distinct thickness dependencies with a broad peak varying from 7 nm to 22 nm depending on the junction sizes, and the large magnetic switching fields favor the stability of the MRAM operation.

  1. Manipulation of a Nuclear Spin by a Magnetic Domain Wall in a Quantum Hall Ferromagnet.

    PubMed

    Korkusinski, M; Hawrylak, P; Liu, H W; Hirayama, Y

    2017-03-06

    The manipulation of a nuclear spin by an electron spin requires the energy to flip the electron spin to be vanishingly small. This can be realized in a many electron system with degenerate ground states of opposite spin polarization in different Landau levels. We present here a microscopic theory of a domain wall between spin unpolarized and spin polarized quantum Hall ferromagnet states at filling factor two with the Zeeman energy comparable to the cyclotron energy. We determine the energies and many-body wave functions of the electronic quantum Hall droplet with up to N = 80 electrons as a function of the total spin, angular momentum, cyclotron and Zeeman energies from the spin singlet ν = 2 phase, through an intermediate polarization state exhibiting a domain wall to the fully spin-polarized phase involving the lowest and the second Landau levels. We demonstrate that the energy needed to flip one electron spin in a domain wall becomes comparable to the energy needed to flip the nuclear spin. The orthogonality of orbital electronic states is overcome by the many-electron character of the domain - the movement of the domain wall relative to the position of the nuclear spin enables the manipulation of the nuclear spin by electrical means.

  2. Manipulation of a Nuclear Spin by a Magnetic Domain Wall in a Quantum Hall Ferromagnet

    PubMed Central

    Korkusinski, M.; Hawrylak, P.; Liu, H. W.; Hirayama, Y.

    2017-01-01

    The manipulation of a nuclear spin by an electron spin requires the energy to flip the electron spin to be vanishingly small. This can be realized in a many electron system with degenerate ground states of opposite spin polarization in different Landau levels. We present here a microscopic theory of a domain wall between spin unpolarized and spin polarized quantum Hall ferromagnet states at filling factor two with the Zeeman energy comparable to the cyclotron energy. We determine the energies and many-body wave functions of the electronic quantum Hall droplet with up to N = 80 electrons as a function of the total spin, angular momentum, cyclotron and Zeeman energies from the spin singlet ν = 2 phase, through an intermediate polarization state exhibiting a domain wall to the fully spin-polarized phase involving the lowest and the second Landau levels. We demonstrate that the energy needed to flip one electron spin in a domain wall becomes comparable to the energy needed to flip the nuclear spin. The orthogonality of orbital electronic states is overcome by the many-electron character of the domain - the movement of the domain wall relative to the position of the nuclear spin enables the manipulation of the nuclear spin by electrical means. PMID:28262758

  3. Imaging domain walls between nematic quantum Hall phases on the surface of bismuth

    NASA Astrophysics Data System (ADS)

    Ding, Hao; Randeria, Mallika T.; Feldman, Benjamin E.; Ji, Huiwen; Cava, Robert J.; Yazdani, Ali

    The sensitivity of nematic electronic phases to disorder results in short range ordering and the formation of domains. Local probes are required to investigate the character of these domains and the boundaries between them, which remain hidden in global measurements that average over microscopic configurations. In this talk, I will describe measurements performed with a scanning tunneling microscope to study local nematic order on the surface of bismuth at high magnetic field. By imaging individual anisotropic cyclotron orbit wavefunctions that are pinned to atomic-scale surface defects, we directly resolve local nematic behavior and study the evolution of nematic states across a domain wall. Through spectroscopic mapping, we explore how the broken-symmetry Landau levels disperse across the domain wall, the influence of exchange interactions at such a boundary, and the formation of one-dimensional edge states.

  4. The α-galactomannan Davanat binds galectin-1 at a site different from the conventional galectin carbohydrate binding domain

    PubMed Central

    Miller, Michelle C; Klyosov, Anatole; Mayo, Kevin H

    2009-01-01

    Galectins are a sub-family of lectins, defined by their highly conserved β-sandwich structures and ability to bind to β-galactosides, like Gal β1-4 Glc (lactose). Here, we used 15N-1H HSQC and pulse field gradient (PFG) NMR spectroscopy to demonstrate that galectin-1 (gal-1) binds to the relatively large galactomannan Davanat, whose backbone is composed of β1-4-linked d-mannopyranosyl units to which single d-galactopyranosyl residues are periodically attached via α1-6 linkage (weight-average MW of 59 kDa). The Davanat binding domain covers a relatively large area on the surface of gal-1 that runs across the dimer interface primarily on that side of the protein opposite to the lactose binding site. Our data show that gal-1 binds Davanat with an apparent equilibrium dissociation constant (Kd) of 10 × 10−6 M, compared to 260 × 10−6 M for lactose, and a stiochiometry of about 3 to 6 gal-1 molecules per Davanat molecule. Mannan also interacts at the same galactomannan binding domain on gal-1, but with at least 10-fold lower avidity, supporting the role of galactose units in Davanat for relatively strong binding to gal-1. We also found that the β-galactoside binding domain remains accessible in the gal-1/Davanat complex, as lactose can still bind with no apparent loss in affinity. In addition, gal-1 binding to Davanat also modifies the supermolecular structure of the galactomannan and appears to reduce its hydrodynamic radius and disrupt inter-glycan interactions thereby reducing glycan-mediated solution viscosity. Overall, our findings contribute to understanding gal-1–carbohydrate interactions and provide insight into gal-1 function with potentially significant biological consequences. PMID:19541770

  5. Structure of the Nucleoprotein Binding Domain of Mokola Virus Phosphoprotein▿

    PubMed Central

    Assenberg, René; Delmas, Olivier; Ren, Jingshan; Vidalain, Pierre-Olivier; Verma, Anil; Larrous, Florence; Graham, Stephen C.; Tangy, Frédéric; Grimes, Jonathan M.; Bourhy, Hervé

    2010-01-01

    Mokola virus (MOKV) is a nonsegmented, negative-sense RNA virus that belongs to the Lyssavirus genus and Rhabdoviridae family. MOKV phosphoprotein P is an essential component of the replication and transcription complex and acts as a cofactor for the viral RNA-dependent RNA polymerase. P recruits the viral polymerase to the nucleoprotein-bound viral RNA (N-RNA) via an interaction between its C-terminal domain and the N-RNA complex. Here we present a structure for this domain of MOKV P, obtained by expression of full-length P in Escherichia coli, which was subsequently truncated during crystallization. The structure has a high degree of homology with P of rabies virus, another member of Lyssavirus genus, and to a lesser degree with P of vesicular stomatitis virus (VSV), a member of the related Vesiculovirus genus. In addition, analysis of the crystal packing of this domain reveals a potential binding site for the nucleoprotein N. Using both site-directed mutagenesis and yeast two-hybrid experiments to measure P-N interaction, we have determined the relative roles of key amino acids involved in this interaction to map the region of P that binds N. This analysis also reveals a structural relationship between the N-RNA binding domain of the P proteins of the Rhabdoviridae and the Paramyxoviridae. PMID:19906936

  6. Mapping the Landscape of Domain-Wall Pinning in Ferromagnetic Films Using Differential Magneto-Optical Microscopy

    NASA Astrophysics Data System (ADS)

    Badea, Robert; Berezovsky, Jesse

    2016-06-01

    The propagation of domain walls in a ferromagnetic film is largely determined by domain-wall pinning at defects in the material. In this article, we map the effective potential landscape for domain-wall pinning in permalloy films by raster scanning a single ferromagnetic vortex and monitoring the hysteretic vortex displacement vs applied magnetic field. The measurement is carried out using a differential magneto-optical microscopy technique which yields spatial sensitivity of approximately 10 nm. We present a simple algorithm for extracting an effective pinning potential from the measurement of vortex displacement vs applied field. The resulting maps of the pinning potential reveal distinct types of pinning sites, which we attribute to quasi-zero-, one-, and two-dimensional defects in the permalloy film.

  7. Multivalent Binding of Formin-binding Protein 21 (FBP21)-Tandem-WW Domains Fosters Protein Recognition in the Pre-spliceosome*

    PubMed Central

    Klippel, Stefan; Wieczorek, Marek; Schümann, Michael; Krause, Eberhard; Marg, Berenice; Seidel, Thorsten; Meyer, Tim; Knapp, Ernst-Walter; Freund, Christian

    2011-01-01

    The high abundance of repetitive but nonidentical proline-rich sequences in spliceosomal proteins raises the question of how these known interaction motifs recruit their interacting protein domains. Whereas complex formation of these adaptors with individual motifs has been studied in great detail, little is known about the binding mode of domains arranged in tandem repeats and long proline-rich sequences including multiple motifs. Here we studied the interaction of the two adjacent WW domains of spliceosomal protein FBP21 with several ligands of different lengths and composition to elucidate the hallmarks of multivalent binding for this class of recognition domains. First, we show that many of the proteins that define the cellular proteome interacting with FBP21-WW1-WW2 contain multiple proline-rich motifs. Among these is the newly identified binding partner SF3B4. Fluorescence resonance energy transfer (FRET) analysis reveals the tandem-WW domains of FBP21 to interact with splicing factor 3B4 (SF3B4) in nuclear speckles where splicing takes place. Isothermal titration calorimetry and NMR shows that the tandem arrangement of WW domains and the multivalency of the proline-rich ligands both contribute to affinity enhancement. However, ligand exchange remains fast compared with the NMR time scale. Surprisingly, a N-terminal spin label attached to a bivalent ligand induces NMR line broadening of signals corresponding to both WW domains of the FBP21-WW1-WW2 protein. This suggests that distinct orientations of the ligand contribute to a delocalized and semispecific binding mode that should facilitate search processes within the spliceosome. PMID:21917930

  8. Magnetic domain-wall tilting due to domain-wall speed asymmetry

    NASA Astrophysics Data System (ADS)

    Kim, Dae-Yun; Park, Min-Ho; Park, Yong-Keun; Kim, Joo-Sung; Nam, Yoon-Seok; Hwang, Hyun-Seok; Kim, Duck-Ho; Je, Soong-Geun; Min, Byoung-Chul; Choe, Sug-Bong

    2018-04-01

    Broken symmetries in diverse systems generate a number of intriguing phenomena and the analysis on such broken symmetries often provides decisive clues for exploring underlying physics in the systems. Recently, in magnetic thin-film systems, the Dzyaloshinskii-Moriya interaction (DMI)—induced by the broken symmetry of structural inversion—accounts for various chiral phenomena, which are of timely issues in spintronics. Here, we report an experimental observation on unexpected tilting of magnetic domain walls (DWs) due to the broken symmetry under the application of the magnetic field transverse to the magnetic wire systems. It has been predicted that the DMI possibly causes such DW tilting in the direction of the energy minimization. However, very interestingly, experimental observation reveals that the DW tilting does not follow the prediction based on the energy minimization, even for the tilting direction. Instead, the DW tilting is governed by the DW speed asymmetry that is initiated by the DW pinning at wire edges. A simple analytic model is proposed in consideration of the DW speed asymmetry at wire edges, which successfully explains the experimental observation of the DW tilting directions and angles, as confirmed by numerical simulation. The present study manifests the decisive role of the DW pinning with the DW speed asymmetry, which determines the DW configuration and consequently, the dynamics.

  9. Phosphorylation-regulated Binding of RNA Polymerase II to Fibrous Polymers of Low Complexity Domains

    PubMed Central

    Xiang, Siheng; Wu, Leeju; Theodoropoulos, Pano; Mirzaei, Hamid; Han, Tina; Xie, Shanhai; Corden, Jeffry L.; McKnight, Steven L.

    2014-01-01

    SUMMARY The low complexity (LC) domains of the products of the fused in sarcoma (FUS), Ewings sarcoma (EWS) and TAF15 genes are translocated onto a variety of different DNA-binding domains and thereby assist in driving the formation of cancerous cells. In the context of the translocated fusion proteins, these LC sequences function as transcriptional activation domains. Here we show that polymeric fibers formed from these LC domains directly bind the C-terminal domain (CTD) of RNA polymerase II in a manner reversible by phosphorylation of the iterated, heptad repeats of the CTD. Mutational analysis indicates that the degree of binding between the CTD and the LC domain polymers correlates with the strength of transcriptional activation. These studies offer a simple means of conceptualizing how RNA polymerase II is recruited to active genes in its unphosphorylated state, and released for elongation following phosphorylation of the CTD. PMID:24267890

  10. BclxL changes conformation upon binding to wild-type but not mutant p53 DNA binding domain.

    PubMed

    Hagn, Franz; Klein, Christian; Demmer, Oliver; Marchenko, Natasha; Vaseva, Angelina; Moll, Ute M; Kessler, Horst

    2010-01-29

    p53 can induce apoptosis through mitochondrial membrane permeabilization by interaction of its DNA binding region with the anti-apoptotic proteins BclxL and Bcl2. However, little is known about the action of p53 at the mitochondria in molecular detail. By using NMR spectroscopy and fluorescence polarization we characterized the binding of wild-type and mutant p53 DNA binding domains to BclxL and show that the wild-type p53 DNA binding domain leads to structural changes in the BH3 binding region of BclxL, whereas mutants fail to induce such effects due to reduced affinity. This was probed by induced chemical shift and residual dipolar coupling data. These data imply that p53 partly achieves its pro-apoptotic function at the mitochondria by facilitating interaction between BclxL and BH3-only proteins in an allosteric mode of action. Furthermore, we characterize for the first time the binding behavior of Pifithrin-mu, a specific small molecule inhibitor of the p53-BclxL interaction, and present a structural model of the protein-ligand complex. A rather unusual behavior is revealed whereby Pifithrin-mu binds to both sides of the protein-protein complex. These data should facilitate the rational design of more potent specific BclxL-p53 inhibitors.

  11. Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor

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

    Peng, Guiqing; Sun, Dawei; Rajashankar, Kanagalaghatta R.

    2011-09-28

    Coronaviruses have evolved diverse mechanisms to recognize different receptors for their cross-species transmission and host-range expansion. Mouse hepatitis coronavirus (MHV) uses the N-terminal domain (NTD) of its spike protein as its receptor-binding domain. Here we present the crystal structure of MHV NTD complexed with its receptor murine carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a). Unexpectedly, MHV NTD contains a core structure that has the same {beta}-sandwich fold as human galectins (S-lectins) and additional structural motifs that bind to the N-terminal Ig-like domain of mCEACAM1a. Despite its galectin fold, MHV NTD does not bind sugars, but instead binds mCEACAM1a through exclusivemore » protein-protein interactions. Critical contacts at the interface have been confirmed by mutagenesis, providing a structural basis for viral and host specificities of coronavirus/CEACAM1 interactions. Sugar-binding assays reveal that galectin-like NTDs of some coronaviruses such as human coronavirus OC43 and bovine coronavirus bind sugars. Structural analysis and mutagenesis localize the sugar-binding site in coronavirus NTDs to be above the {beta}-sandwich core. We propose that coronavirus NTDs originated from a host galectin and retained sugar-binding functions in some contemporary coronaviruses, but evolved new structural features in MHV for mCEACAM1a binding.« less

  12. Nucleic acids encoding a cellulose binding domain

    DOEpatents

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1996-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  13. Nucleic acids encoding a cellulose binding domain

    DOEpatents

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1996-03-05

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 15 figs.

  14. Rise of Racetrack Memory! Domain Wall Spin-Orbitronics

    NASA Astrophysics Data System (ADS)

    Parkin, Stuart

    Memory-storage devices based on the current controlled motion of a series of domain walls (DWs) in magnetic racetracks promise performance and reliability beyond that of conventional magnetic disk drives and solid state storage devices (1). Racetracks that are formed from atomically thin, perpendicularly magnetized nano-wires, interfaced with adjacent metal layers with high spin-orbit coupling, give rise to domain walls that exhibit a chiral Néel structure (2). These DWs can be moved very efficiently with current via chiral spin-orbit torques (2,3). Record-breaking current-induced DW speeds exceeding 1,000 m/sec are found in synthetic antiferromagnetic structures (3) in which the net magnetization of the DWs is tuned to almost zero, making them ``invisible''. Based on these recent discoveries, Racetrack Memory devices have the potential to operate on picosecond timescales and at densities more than 100 times greater than other memory technologies. (1) S.S.P. Parkin et al., Science 320, 5873 (2008); S.S.P. Parkin and S.-H. Yang, Nat. Nano. 10, 195 (2015). (2) K.-S. Ryu metal. Nat. Nano. 8, 527 (2013). (3) S.-H. Yang, K.-S. Ryu and S.S.P. Parkin, Nat. Nano. 10, 221 (2015). (4). S.S.P. Parkin, Phys. Rev. Lett. 67, 3598 (1991).

  15. Substrate clamping effects on irreversible domain wall dynamics in lead zirconate titanate thin films.

    PubMed

    Griggio, F; Jesse, S; Kumar, A; Ovchinnikov, O; Kim, H; Jackson, T N; Damjanovic, D; Kalinin, S V; Trolier-McKinstry, S

    2012-04-13

    The role of long-range strain interactions on domain wall dynamics is explored through macroscopic and local measurements of nonlinear behavior in mechanically clamped and released polycrystalline lead zirconate-titanate (PZT) films. Released films show a dramatic change in the global dielectric nonlinearity and its frequency dependence as a function of mechanical clamping. Furthermore, we observe a transition from strong clustering of the nonlinear response for the clamped case to almost uniform nonlinearity for the released film. This behavior is ascribed to increased mobility of domain walls. These results suggest the dominant role of collective strain interactions mediated by the local and global mechanical boundary conditions on the domain wall dynamics. The work presented in this Letter demonstrates that measurements on clamped films may considerably underestimate the piezoelectric coefficients and coupling constants of released structures used in microelectromechanical systems, energy harvesting systems, and microrobots.

  16. Lipid binding by the Unique and SH3 domains of c-Src suggests a new regulatory mechanism

    PubMed Central

    Pérez, Yolanda; Maffei, Mariano; Igea, Ana; Amata, Irene; Gairí, Margarida; Nebreda, Angel R.; Bernadó, Pau; Pons, Miquel

    2013-01-01

    c-Src is a non-receptor tyrosine kinase involved in numerous signal transduction pathways. The kinase, SH3 and SH2 domains of c-Src are attached to the membrane-anchoring SH4 domain through the flexible Unique domain. Here we show intra- and intermolecular interactions involving the Unique and SH3 domains suggesting the presence of a previously unrecognized additional regulation layer in c-Src. We have characterized lipid binding by the Unique and SH3 domains, their intramolecular interaction and its allosteric modulation by a SH3-binding peptide or by Calcium-loaded calmodulin binding to the Unique domain. We also show reduced lipid binding following phosphorylation at conserved sites of the Unique domain. Finally, we show that injection of full-length c-Src with mutations that abolish lipid binding by the Unique domain causes a strong in vivo phenotype distinct from that of wild-type c-Src in a Xenopus oocyte model system, confirming the functional role of the Unique domain in c-Src regulation. PMID:23416516

  17. In vivo binding properties of SH2 domains from GTPase-activating protein and phosphatidylinositol 3-kinase.

    PubMed Central

    Cooper, J A; Kashishian, A

    1993-01-01

    We have used a transient expression system and mutant platelet-derived growth factor (PDGF) receptors to study the binding specificities of the Src homology 2 (SH2) regions of the Ras GTPase-activator protein (GAP) and the p85 alpha subunit of phosphatidylinositol 3-kinase (PI3 kinase). A number of fusion proteins, each tagged with an epitope allowing recognition by a monoclonal antibody, were expressed at levels comparable to those of endogenous GAP. Fusion proteins containing the central SH2-SH3-SH2 region of GAP or the C-terminal region of p85 alpha, which includes two SH2 domains, bound to PDGF receptors in response to PDGF stimulation. Both fusion proteins showed the same requirements for tyrosine phosphorylation sites in the PDGF receptor as the full-length proteins from which they were derived, i.e., binding of the GAP fusion protein was reduced by mutation of Tyr-771, and binding of the p85 fusion protein was reduced by mutation of Tyr-740, Tyr-751, or both residues. Fusion proteins containing single SH2 domains from either GAP or p85 alpha did not bind detectably to PDGF receptors in this system, suggesting that two SH2 domains in a single polypeptide cooperate to raise the affinity of binding. The sequence specificities of individual SH2 domains were deduced from the binding properties of fusion proteins containing one SH2 domain from GAP and another from p85. The results suggest that the C-terminal GAP SH2 domain specifies binding to Tyr-771, the C-terminal p85 alpha SH2 domain binds to either Tyr-740 or Tyr-751, and each protein's N-terminal SH2 domain binds to unidentified phosphorylation sites.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8382774

  18. Magnetoresistance due to domain walls in an epitaxial microfabricated Fe wire

    NASA Astrophysics Data System (ADS)

    Rüdiger, U.; Yu, J.; Kent, A. D.; Parkin, S. S. P.

    1998-08-01

    The domain wall (DW) contribution to magnetoresistance has been investigated using an epitaxial microfabricated bcc (110) Fe wires of 2 μm linewidth. A strong in-plane uniaxial component to the magnetic anisotropy perpendicular to the wire axis causes a regular stripe domain pattern with closure domains. The stripe domain width in zero-applied magnetic field is strongly affected by the magnetic history and can be continuously varied from 0.45 to 1.8 μm. This enables a measurement of the resistivity as a function of DW density in a single wire. Clear evidence is presented that the resistivity is reduced in the presence of DWs at low temperatures.

  19. A ternary metal binding site in the C2 domain of phosphoinositide-specific phospholipase C-delta1.

    PubMed

    Essen, L O; Perisic, O; Lynch, D E; Katan, M; Williams, R L

    1997-03-11

    We have determined the crystal structures of complexes of phosphoinositide-specific phospholipase C-delta1 from rat with calcium, barium, and lanthanum at 2.5-2.6 A resolution. Binding of these metal ions is observed in the active site of the catalytic TIM barrel and in the calcium binding region (CBR) of the C2 domain. The C2 domain of PLC-delta1 is a circularly permuted topological variant (P-variant) of the synaptotagmin I C2A domain (S-variant). On the basis of sequence analysis, we propose that both the S-variant and P-variant topologies are present among other C2 domains. Multiple adjacent binding sites in the C2 domain were observed for calcium and the other metal/enzyme complexes. The maximum number of binding sites observed was for the calcium analogue lanthanum. This complex shows an array-like binding of three lanthanum ions (sites I-III) in a crevice on one end of the C2 beta-sandwich. Residues involved in metal binding are contained in three loops, CBR1, CBR2, and CBR3. Sites I and II are maintained in the calcium and barium complexes, whereas sites II and III coincide with a binary calcium binding site in the C2A domain of synaptotagmin I. Several conformers for CBR1 are observed. The conformation of CBR1 does not appear to be strictly dependent on metal binding; however, metal binding may stabilize certain conformers. No significant structural changes are observed for CBR2 or CBR3. The surface of this ternary binding site provides a cluster of freely accessible liganding positions for putative phospholipid ligands of the C2 domain. It may be that the ternary metal binding site is also a feature of calcium-dependent phospholipid binding in solution. A ternary metal binding site might be a conserved feature among C2 domains that contain the critical calcium ligands in their CBR's. The high cooperativity of calcium-mediated lipid binding by C2 domains described previously is explained by this novel type of calcium binding site.

  20. Ratchet Effects and Domain Wall Energy Landscapes in Amorphous Magnetic Films with 2D Arrays of Asymmetric Holes

    NASA Astrophysics Data System (ADS)

    Martin, J. I.; Alija, A.; Sobrado, I.; Perez-Junquera, A.; Rodriguez-Rodriguez, G.; Velez, M.; Alameda, J. M.; Marconi, V. I.; Kolton, A. B.; Parrondo, J. M. R.

    2009-03-01

    The driven motion of domain walls in extended magnetic films patterned with 2D arrays of asymmetric holes has been found to be subject to two different crossed ratchet effects [1] which results in an inversion of the sign of domain wall motion rectification as a function of the applied magnetic field. This effect can be understood in terms of the competition between drive, elasticity and asymmetric pinning as revealed by a simple 4̂-model. In order to optimize the asymmetric hole design, the relevant energy landscapes for domain wall motion across the array of asymmetric holes have been calculated by micromagnetic simulations as a function of array geometrical characteristics. The effects of a transverse magnetic field on these two crossed ratchet effects will also be discussed in terms of the decrease in domain wall energy per unit area and of the modifications in the magnetostatic barriers for domain wall pinning at the asymmetric inclusions. Work supported by Spanish MICINN.[1] A. Perez-Junquera et al, Phys. Rev. Lett. 100 (2008) 037203

  1. The Role of Flexibility and Conformational Selection in the Binding Promiscuity of PDZ Domains

    PubMed Central

    Münz, Márton; Hein, Jotun; Biggin, Philip C.

    2012-01-01

    In molecular recognition, it is often the case that ligand binding is coupled to conformational change in one or both of the binding partners. Two hypotheses describe the limiting cases involved; the first is the induced fit and the second is the conformational selection model. The conformational selection model requires that the protein adopts conformations that are similar to the ligand-bound conformation in the absence of ligand, whilst the induced-fit model predicts that the ligand-bound conformation of the protein is only accessible when the ligand is actually bound. The flexibility of the apo protein clearly plays a major role in these interpretations. For many proteins involved in signaling pathways there is the added complication that they are often promiscuous in that they are capable of binding to different ligand partners. The relationship between protein flexibility and promiscuity is an area of active research and is perhaps best exemplified by the PDZ domain family of proteins. In this study we use molecular dynamics simulations to examine the relationship between flexibility and promiscuity in five PDZ domains: the human Dvl2 (Dishevelled-2) PDZ domain, the human Erbin PDZ domain, the PDZ1 domain of InaD (inactivation no after-potential D protein) from fruit fly, the PDZ7 domain of GRIP1 (glutamate receptor interacting protein 1) from rat and the PDZ2 domain of PTP-BL (protein tyrosine phosphatase) from mouse. We show that despite their high structural similarity, the PDZ binding sites have significantly different dynamics. Importantly, the degree of binding pocket flexibility was found to be closely related to the various characteristics of peptide binding specificity and promiscuity of the five PDZ domains. Our findings suggest that the intrinsic motions of the apo structures play a key role in distinguishing functional properties of different PDZ domains and allow us to make predictions that can be experimentally tested. PMID:23133356

  2. Chimeric Plant Calcium/Calmodulin-Dependent Protein Kinase Gene with a Neural Visinin-Like Calcium-Binding Domain

    NASA Technical Reports Server (NTRS)

    Patil, Shameekumar; Takezawa, D.; Poovaiah, B. W.

    1995-01-01

    Calcium, a universal second messenger, regulates diverse cellular processes in eukaryotes. Ca-2(+) and Ca-2(+)/calmodulin-regulated protein phosphorylation play a pivotal role in amplifying and diversifying the action of Ca-2(+)- mediated signals. A chimeric Ca-2(+)/calmodulin-dependent protein kinase (CCaMK) gene with a visinin-like Ca-2(+)- binding domain was cloned and characterized from lily. The cDNA clone contains an open reading frame coding for a protein of 520 amino acids. The predicted structure of CCaMK contains a catalytic domain followed by two regulatory domains, a calmodulin-binding domain and a visinin-like Ca-2(+)-binding domain. The amino-terminal region of CCaMK contains all 11 conserved subdomains characteristic of serine/threonine protein kinases. The calmodulin-binding region of CCaMK has high homology (79%) to alpha subunit of mammalian Ca-2(+)/calmodulin-dependent protein kinase. The calmodulin-binding region is fused to a neural visinin-like domain that contains three Ca-2(+)-binding EF-hand motifs and a biotin-binding site. The Escherichia coli-expressed protein (approx. 56 kDa) binds calmodulin in a Ca-2(+)-dependent manner. Furthermore, Ca-45-binding assays revealed that CCaMK directly binds Ca-2(+). The CCaMK gene is preferentially expressed in developing anthers. Southern blot analysis revealed that CCaMK is encoded by a single gene. The structural features of the gene suggest that it has multiple regulatory controls and could play a unique role in Ca-2(+) signaling in plants.

  3. Solution structure of the Big domain from Streptococcus pneumoniae reveals a novel Ca2+-binding module

    PubMed Central

    Wang, Tao; Zhang, Jiahai; Zhang, Xuecheng; Xu, Chao; Tu, Xiaoming

    2013-01-01

    Streptococcus pneumoniae is a pathogen causing acute respiratory infection, otitis media and some other severe diseases in human. In this study, the solution structure of a bacterial immunoglobulin-like (Big) domain from a putative S. pneumoniae surface protein SP0498 was determined by NMR spectroscopy. SP0498 Big domain adopts an eight-β-strand barrel-like fold, which is different in some aspects from the two-sheet sandwich-like fold of the canonical Ig-like domains. Intriguingly, we identified that the SP0498 Big domain was a Ca2+ binding domain. The structure of the Big domain is different from those of the well known Ca2+ binding domains, therefore revealing a novel Ca2+-binding module. Furthermore, we identified the critical residues responsible for the binding to Ca2+. We are the first to report the interactions between the Big domain and Ca2+ in terms of structure, suggesting an important role of the Big domain in many essential calcium-dependent cellular processes such as pathogenesis. PMID:23326635

  4. Domain-wall superconductivity in superconductor-ferromagnet hybrids.

    PubMed

    Yang, Zhaorong; Lange, Martin; Volodin, Alexander; Szymczak, Ritta; Moshchalkov, Victor V

    2004-11-01

    Superconductivity and magnetism are two antagonistic cooperative phenomena, and the intriguing problem of their coexistence has been studied for several decades. Recently, artificial hybrid superconductor-ferromagnet systems have been commonly used as model systems to reveal the interplay between competing superconducting and magnetic order parameters, and to verify the existence of new physical phenomena, including the predicted domain-wall superconductivity (DWS). Here we report the experimental observation of DWS in superconductor-ferromagnet hybrids using a niobium film on a BaFe(12)O(19) single crystal. We found that the critical temperature T(c) of the superconductivity nucleation in niobium increases with increasing field until it reaches the saturation field of BaFe(12)O(19). In accordance with the field-shift of the maximum value of T(c), pronounced hysteresis effects have been found in resistive transitions. We argue that the compensation of the applied field by the stray fields of the magnetic domains as well as the change in the domain structure is responsible for the appearance of the DWS and the coexistence of superconductivity and magnetism in the superconductor-ferromagnet hybrids.

  5. Intrinsic Pleckstrin Homology (PH) Domain Motion in Phospholipase C-β Exposes a Gβγ Protein Binding Site*

    PubMed Central

    Kadamur, Ganesh

    2016-01-01

    Mammalian phospholipase C-β (PLC-β) isoforms are stimulated by heterotrimeric G protein subunits and members of the Rho GTPase family of small G proteins. Although recent structural studies showed how Gαq and Rac1 bind PLC-β, there is a lack of consensus regarding the Gβγ binding site in PLC-β. Using FRET between cerulean fluorescent protein-labeled Gβγ and the Alexa Fluor 594-labeled PLC-β pleckstrin homology (PH) domain, we demonstrate that the PH domain is the minimal Gβγ binding region in PLC-β3. We show that the isolated PH domain can compete with full-length PLC-β3 for binding Gβγ but not Gαq, Using sequence conservation, structural analyses, and mutagenesis, we identify a hydrophobic face of the PLC-β PH domain as the Gβγ binding interface. This PH domain surface is not solvent-exposed in crystal structures of PLC-β, necessitating conformational rearrangement to allow Gβγ binding. Blocking PH domain motion in PLC-β by cross-linking it to the EF hand domain inhibits stimulation by Gβγ without altering basal activity or Gαq response. The fraction of PLC-β cross-linked is proportional to the fractional loss of Gβγ response. Cross-linked PLC-β does not bind Gβγ in a FRET-based Gβγ-PLC-β binding assay. We propose that unliganded PLC-β exists in equilibrium between a closed conformation observed in crystal structures and an open conformation where the PH domain moves away from the EF hands. Therefore, intrinsic movement of the PH domain in PLC-β modulates Gβγ access to its binding site. PMID:27002154

  6. Kinase Associated-1 Domains Drive MARK/PAR1 Kinases to Membrane Targets by Binding Acidic Phospholipids

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

    Moravcevic, Katarina; Mendrola, Jeannine M.; Schmitz, Karl R.

    Phospholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regulation of many protein kinases. Here, we identify the KA1 domain (kinase associated-1 domain), found at the C terminus of yeast septin-associated kinases (Kcc4p, Gin4p, and Hsl1p) and human MARK/PAR1 kinases, as a membrane association domain that binds acidic phospholipids. Membrane localization of isolated KA1 domains depends on phosphatidylserine. Using X-ray crystallography, we identified a structurally conserved binding site for anionic phospholipids in KA1 domains from Kcc4p and MARK1. Mutating this site impairs membrane association of both KA1 domains and intact proteins and reveals the importancemore » of phosphatidylserine for bud neck localization of yeast Kcc4p. Our data suggest that KA1 domains contribute to coincidence detection, allowing kinases to bind other regulators (such as septins) only at the membrane surface. These findings have important implications for understanding MARK/PAR1 kinases, which are implicated in Alzheimer's disease, cancer, and autism.« less

  7. Structural insights into the specific binding of huntingtin proline-rich region with the SH3 and WW domains.

    PubMed

    Gao, Yong-Guang; Yan, Xian-Zhong; Song, Ai-Xin; Chang, Yong-Gang; Gao, Xue-Chao; Jiang, Nan; Zhang, Qi; Hu, Hong-Yu

    2006-12-01

    The interactions of huntingtin (Htt) with the SH3 domain- or WW domain-containing proteins have been implicated in the pathogenesis of Huntington's disease (HD). We report the specific interactions of Htt proline-rich region (PRR) with the SH3GL3-SH3 domain and HYPA-WW1-2 domain pair by NMR. The results show that Htt PRR binds with the SH3 domain through nearly its entire chain, and that the binding region on the domain includes the canonical PxxP-binding site and the specificity pocket. The C terminus of PRR orients to the specificity pocket, whereas the N terminus orients to the PxxP-binding site. Htt PRR can also specifically bind to WW1-2; the N-terminal portion preferentially binds to WW1, while the C-terminal portion binds to WW2. This study provides structural insights into the specific interactions between Htt PRR and its binding partners as well as the alteration of these interactions that involve PRR, which may have implications for the understanding of HD.

  8. Enhanced sampling of glutamate receptor ligand-binding domains.

    PubMed

    Lau, Albert Y

    2018-04-14

    The majority of excitatory synaptic transmission in the central nervous system is mediated by ionotropic glutamate receptors (iGluRs). These membrane-bound protein assemblies consist of modular domains that can be genetically isolated and expressed, which has resulted in a plethora of crystal structures of individual domains in different conformations bound to different ligands. These structures have presented opportunities for molecular dynamics (MD) simulation studies. To examine the free energies that govern molecular behavior, simulation strategies and algorithms have been developed, collectively called enhanced sampling methods This review focuses on the use of enhanced sampling MD simulations of isolated iGluR ligand-binding domains to characterize thermodynamic properties important to receptor function. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Direct observation of charged domain walls in hybrid improper ferroelectric (Ca,Sr)3Ti2O7

    NASA Astrophysics Data System (ADS)

    Kurushima, Kousuke; Yoshimoto, Wataru; Ishii, Yui; Cheong, Sang-Wook; Mori, Shigeo

    2017-10-01

    We investigated ferroelectric (FE) domain wall structures including “charged domain walls” of hybrid improper FE (Ca,Sr)3Ti2O7 at the subatomic resolution by dark-field transmission electron microscopy (TEM) and high-resolution state-of-the-art aberration-corrected high-angle annular-dark-field (HAADF) scanning transmission electron microscopy (STEM). Dark-field TEM and high-resolution HAADF-STEM images obtained in the FE phase of single crystals of Ca2.46Sr0.54Ti2O7 revealed the formation of abundant charged domain walls with the head-to-head and tail-to-tail configurations in the FE domain structure, in addition to the FE 180° domain structure. The charged domain walls with the head-to-head and tail-to-tail FE polarizations exist stably and can be characterized as the unique double arc-type displacement of Ca/Sr ions in a unit cell without charge accumulation.

  10. Characterization of diverse internal binding specificities of PDZ domains by yeast two-hybrid screening of a special peptide library.

    PubMed

    Mu, Yi; Cai, Pengfei; Hu, Siqi; Ma, Sucan; Gao, Youhe

    2014-01-01

    Protein-protein interactions (PPIs) are essential events to play important roles in a series of biological processes. There are probably more ways of PPIs than we currently realized. Structural and functional investigations of weak PPIs have lagged behind those of strong PPIs due to technical difficulties. Weak PPIs are often short-lived, which may result in more dynamic signals with important biological roles within and/or between cells. For example, the characteristics of PSD-95/Dlg/ZO-1 (PDZ) domain binding to internal sequences, which are primarily weak interactions, have not yet been systematically explored. In the present study, we constructed a nearly random octapeptide yeast two-hybrid library. A total of 24 PDZ domains were used as baits for screening the library. Fourteen of these domains were able to bind internal PDZ-domain binding motifs (PBMs), and PBMs screened for nine PDZ domains exhibited strong preferences. Among 11 PDZ domains that have not been reported their internal PBM binding ability, six were confirmed to bind internal PBMs. The first PDZ domain of LNX2, which has not been reported to bind C-terminal PBMs, was found to bind internal PBMs. These results suggest that the internal PBMs binding ability of PDZ domains may have been underestimated. The data provided diverse internal binding properties for several PDZ domains that may help identify their novel binding partners.

  11. Abundance, diversity and domain architecture variability in prokaryotic DNA-binding transcription factors.

    PubMed

    Perez-Rueda, Ernesto; Hernandez-Guerrero, Rafael; Martinez-Nuñez, Mario Alberto; Armenta-Medina, Dagoberto; Sanchez, Israel; Ibarra, J Antonio

    2018-01-01

    Gene regulation at the transcriptional level is a central process in all organisms, and DNA-binding transcription factors, known as TFs, play a fundamental role. This class of proteins usually binds at specific DNA sequences, activating or repressing gene expression. In general, TFs are composed of two domains: the DNA-binding domain (DBD) and an extra domain, which in this work we have named "companion domain" (CD). This latter could be involved in one or more functions such as ligand binding, protein-protein interactions or even with enzymatic activity. In contrast to DBDs, which have been widely characterized both experimentally and bioinformatically, information on the abundance, distribution, variability and possible role of the CDs is scarce. Here, we investigated these issues associated with the domain architectures of TFs in prokaryotic genomes. To this end, 19 families of TFs in 761 non-redundant bacterial and archaeal genomes were evaluated. In this regard we found four main groups based on the abundance and distribution in the analyzed genomes: i) LysR and TetR/AcrR; ii) AraC/XylS, SinR, and others; iii) Lrp, Fis, ArsR, and others; and iv) a group that included only two families, ArgR and BirA. Based on a classification of the organisms according to the life-styles, a major abundance of regulatory families in free-living organisms, in contrast with pathogenic, extremophilic or intracellular organisms, was identified. Finally, the protein architecture diversity associated to the 19 families considering a weight score for domain promiscuity evidenced which regulatory families were characterized by either a large diversity of CDs, here named as "promiscuous" families given the elevated number of variable domains found in those TFs, or a low diversity of CDs. Altogether this information helped us to understand the diversity and distribution of the 19 Prokaryotes TF families. Moreover, initial steps were taken to comprehend the variability of the extra domain

  12. Intrinsic Pleckstrin Homology (PH) Domain Motion in Phospholipase C-β Exposes a Gβγ Protein Binding Site.

    PubMed

    Kadamur, Ganesh; Ross, Elliott M

    2016-05-20

    Mammalian phospholipase C-β (PLC-β) isoforms are stimulated by heterotrimeric G protein subunits and members of the Rho GTPase family of small G proteins. Although recent structural studies showed how Gαq and Rac1 bind PLC-β, there is a lack of consensus regarding the Gβγ binding site in PLC-β. Using FRET between cerulean fluorescent protein-labeled Gβγ and the Alexa Fluor 594-labeled PLC-β pleckstrin homology (PH) domain, we demonstrate that the PH domain is the minimal Gβγ binding region in PLC-β3. We show that the isolated PH domain can compete with full-length PLC-β3 for binding Gβγ but not Gαq, Using sequence conservation, structural analyses, and mutagenesis, we identify a hydrophobic face of the PLC-β PH domain as the Gβγ binding interface. This PH domain surface is not solvent-exposed in crystal structures of PLC-β, necessitating conformational rearrangement to allow Gβγ binding. Blocking PH domain motion in PLC-β by cross-linking it to the EF hand domain inhibits stimulation by Gβγ without altering basal activity or Gαq response. The fraction of PLC-β cross-linked is proportional to the fractional loss of Gβγ response. Cross-linked PLC-β does not bind Gβγ in a FRET-based Gβγ-PLC-β binding assay. We propose that unliganded PLC-β exists in equilibrium between a closed conformation observed in crystal structures and an open conformation where the PH domain moves away from the EF hands. Therefore, intrinsic movement of the PH domain in PLC-β modulates Gβγ access to its binding site. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Mobius domain-wall fermions on gradient-flowed dynamical HISQ ensembles

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

    Berkowitz, Evan; Bouchard, Chris; Chang, Chia Cheng

    Here, we report on salient features of a mixed lattice QCD action using valence M\\"{o}bius domain-wall fermions solved on the dynamicalmore » $$N_f=2+1+1$$ HISQ ensembles generated by the MILC Collaboration. The approximate chiral symmetry properties of the valence fermions are shown to be significantly improved by utilizing the gradient-flow scheme to first smear the HISQ configurations. The greater numerical cost of the M\\"{o}bius domain-wall inversions is mitigated by the highly efficient QUDA library optimized for NVIDIA GPU accelerated compute nodes. We have created an interface to this optimized QUDA solver in Chroma. We provide tuned parameters of the action and performance of QUDA using ensembles with the lattice spacings $$a \\simeq \\{0.15, 0.12, 0.09\\}$$ fm and pion masses $$m_\\pi \\simeq \\{310, 220,130\\}$$ MeV. We have additionally generated two new ensembles with $$a\\sim0.12$$ fm and $$m_\\pi\\sim\\{400, 350\\}$$ MeV. With a fixed flow-time of $$t_{gf}=1$$ in lattice units, the residual chiral symmetry breaking of the valence fermions is kept below 10\\% of the light quark mass on all ensembles, $$m_{res} \\lesssim 0.1\\times m_l$$, with moderate values of the fifth dimension $$L_5$$ and a domain-wall height $$M_5 \\leq 1.3$$. As a benchmark calculation, we perform a continuum, infinite volume, physical pion and kaon mass extrapolation of $$F_{K^\\pm}/F_{\\pi^\\pm}$$ and demonstrate our results are independent of flow-time, and consistent with the FLAG determination of this quantity at the level of less than one standard deviation.« less

  14. Mobius domain-wall fermions on gradient-flowed dynamical HISQ ensembles

    DOE PAGES

    Berkowitz, Evan; Bouchard, Chris; Chang, Chia Cheng; ...

    2017-09-25

    Here, we report on salient features of a mixed lattice QCD action using valence M\\"{o}bius domain-wall fermions solved on the dynamicalmore » $$N_f=2+1+1$$ HISQ ensembles generated by the MILC Collaboration. The approximate chiral symmetry properties of the valence fermions are shown to be significantly improved by utilizing the gradient-flow scheme to first smear the HISQ configurations. The greater numerical cost of the M\\"{o}bius domain-wall inversions is mitigated by the highly efficient QUDA library optimized for NVIDIA GPU accelerated compute nodes. We have created an interface to this optimized QUDA solver in Chroma. We provide tuned parameters of the action and performance of QUDA using ensembles with the lattice spacings $$a \\simeq \\{0.15, 0.12, 0.09\\}$$ fm and pion masses $$m_\\pi \\simeq \\{310, 220,130\\}$$ MeV. We have additionally generated two new ensembles with $$a\\sim0.12$$ fm and $$m_\\pi\\sim\\{400, 350\\}$$ MeV. With a fixed flow-time of $$t_{gf}=1$$ in lattice units, the residual chiral symmetry breaking of the valence fermions is kept below 10\\% of the light quark mass on all ensembles, $$m_{res} \\lesssim 0.1\\times m_l$$, with moderate values of the fifth dimension $$L_5$$ and a domain-wall height $$M_5 \\leq 1.3$$. As a benchmark calculation, we perform a continuum, infinite volume, physical pion and kaon mass extrapolation of $$F_{K^\\pm}/F_{\\pi^\\pm}$$ and demonstrate our results are independent of flow-time, and consistent with the FLAG determination of this quantity at the level of less than one standard deviation.« less

  15. Alternative dimerization interfaces in the glucocorticoid receptor-α ligand binding domain.

    PubMed

    Bianchetti, Laurent; Wassmer, Bianca; Defosset, Audrey; Smertina, Anna; Tiberti, Marion L; Stote, Roland H; Dejaegere, Annick

    2018-04-30

    Nuclear hormone receptors (NRs) constitute a large family of multi-domain ligand-activated transcription factors. Dimerization is essential for their regulation, and both DNA binding domain (DBD) and ligand binding domain (LBD) are implicated in dimerization. Intriguingly, the glucocorticoid receptor-α (GRα) presents a DBD dimeric architecture similar to that of the homologous estrogen receptor-α (ERα), but an atypical dimeric architecture for the LBD. The physiological relevance of the proposed GRα LBD dimer is a subject of debate. We analyzed all GRα LBD homodimers observed in crystals using an energetic analysis based on the PISA and on the MM/PBSA methods and a sequence conservation analysis, using the ERα LBD dimer as a reference point. Several dimeric assemblies were observed for GRα LBD. The assembly generally taken to be physiologically relevant showed weak binding free energy and no significant residue conservation at the contact interface, while an alternative homodimer mediated by both helix 9 and C-terminal residues showed significant binding free energy and residue conservation. However, none of the GRα LBD assemblies found in crystals are as stable or conserved as the canonical ERα LBD dimer. GRα C-terminal sequence (F-domain) forms a steric obstacle to the canonical dimer assembly in all available structures. Our analysis calls for a re-examination of the currently accepted GRα homodimer structure and experimental investigations of the alternative architectures. This work questions the validity of the currently accepted architecture. This has implications for interpreting physiological data and for therapeutic design pertaining to glucocorticoid research. Copyright © 2018. Published by Elsevier B.V.

  16. Optical, electrical and elastic properties of ferroelectric domain walls in lithium niobate and lithium titanate

    NASA Astrophysics Data System (ADS)

    Kim, Sungwon

    Ferroelectric LiNbO3 and LiTaO3 crystals have developed, over the last 50 years as key materials for integrated and nonlinear optics due to their large electro-optic and nonlinear optical coefficients and a broad transparency range from 0.4 mum-4.5 mum wavelengths. Applications include high speed optical modulation and switching in 40GHz range, second harmonic generation, optical parametric amplification, pulse compression and so on. Ferroelectric domain microengineering has led to electro-optic scanners, dynamic focusing lenses, total internal reflection switches, and quasi-phase matched (QPM) frequency doublers. Most of these applications have so far been on non-stoichiometric compositions of these crystals. Recent breakthroughs in crystal growth have however opened up an entirely new window of opportunity from both scientific and technological viewpoint. The growth of stoichiometric composition crystals has led to the discovery of many fascinating effects arising from the presence or absence of atomic defects, such as an order of magnitude changes in coercive fields, internal fields, domain backswitching and stabilization phenomenon. On the nanoscale, unexpected features such as the presence of wide regions of optical contrast and strain have been discovered at 180° domain walls. Such strong influence of small amounts of nonstoichiometric defects on material properties has led to new device applications, particularly those involving domain patterning and shaping such as QPM devices in thick bulk crystals and improved photorefractive damage compositions. The central focus of this dissertation is to explore the role of nonstoichiometry and its precise influence on macroscale and nanoscale properties in lithium niobate and tantalate. Macroscale properties are studied using a combination of in-situ and high-speed electro-optic imaging microscopy and electrical switching experiments. Local static and dynamic strain properties at individual domain walls is studied

  17. Conformational Control of the Binding of the Transactivation Domain of the MLL Protein and c-Myb to the KIX Domain of CREB

    PubMed Central

    Korkmaz, Elif Nihal; Nussinov, Ruth; Haliloğlu, Türkan

    2012-01-01

    The KIX domain of CBP is a transcriptional coactivator. Concomitant binding to the activation domain of proto-oncogene protein c-Myb and the transactivation domain of the trithorax group protein mixed lineage leukemia (MLL) transcription factor lead to the biologically active ternary MLL∶KIX∶c-Myb complex which plays a role in Pol II-mediated transcription. The binding of the activation domain of MLL to KIX enhances c-Myb binding. Here we carried out molecular dynamics (MD) simulations for the MLL∶KIX∶c-Myb ternary complex, its binary components and KIX with the goal of providing a mechanistic explanation for the experimental observations. The dynamic behavior revealed that the MLL binding site is allosterically coupled to the c-Myb binding site. MLL binding redistributes the conformational ensemble of KIX, leading to higher populations of states which favor c-Myb binding. The key element in the allosteric communication pathways is the KIX loop, which acts as a control mechanism to enhance subsequent binding events. We tested this conclusion by in silico mutations of loop residues in the KIX∶MLL complex and by comparing wild type and mutant dynamics through MD simulations. The loop assumed MLL binding conformation similar to that observed in the KIX∶c-Myb state which disfavors the allosteric network. The coupling with c-Myb binding site faded, abolishing the positive cooperativity observed in the presence of MLL. Our major conclusion is that by eliciting a loop-mediated allosteric switch between the different states following the binding events, transcriptional activation can be regulated. The KIX system presents an example how nature makes use of conformational control in higher level regulation of transcriptional activity and thus cellular events. PMID:22438798

  18. Domain-Swapped Dimers of Intracellular Lipid-Binding Proteins: Evidence for Ordered Folding Intermediates.

    PubMed

    Assar, Zahra; Nossoni, Zahra; Wang, Wenjing; Santos, Elizabeth M; Kramer, Kevin; McCornack, Colin; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James H

    2016-09-06

    Human Cellular Retinol Binding Protein II (hCRBPII), a member of the intracellular lipid-binding protein family, is a monomeric protein responsible for the intracellular transport of retinol and retinal. Herein we report that hCRBPII forms an extensive domain-swapped dimer during bacterial expression. The domain-swapped region encompasses almost half of the protein. The dimer represents a novel structural architecture with the mouths of the two binding cavities facing each other, producing a new binding cavity that spans the length of the protein complex. Although wild-type hCRBPII forms the dimer, the propensity for dimerization can be substantially increased via mutation at Tyr60. The monomeric form of the wild-type protein represents the thermodynamically more stable species, making the domain-swapped dimer a kinetically trapped entity. Hypothetically, the wild-type protein has evolved to minimize dimerization of the folding intermediate through a critical hydrogen bond (Tyr60-Glu72) that disfavors the dimeric form. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Low field domain wall dynamics in artificial spin-ice basis structure

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

    Kwon, J.; School of Electrical and Electronic Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798; Goolaup, S.

    2015-10-28

    Artificial magnetic spin-ice nanostructures provide an ideal platform for the observation of magnetic monopoles. The formation of a magnetic monopole is governed by the motion of a magnetic charge carrier via the propagation of domain walls (DWs) in a lattice. To date, most experiments have been on the static visualization of DW propagation in the lattice. In this paper, we report on the low field dynamics of DW in a unit spin-ice structure measured by magnetoresistance changes. Our results show that reversible DW propagation can be initiated within the spin-ice basis. The initial magnetization configuration of the unit structure stronglymore » influences the direction of DW motion in the branches. Single or multiple domain wall nucleation can be induced in the respective branches of the unit spin ice by the direction of the applied field.« less

  20. Proteolytic dissection of Zab, the Z-DNA-binding domain of human ADAR1

    NASA Technical Reports Server (NTRS)

    Schwartz, T.; Lowenhaupt, K.; Kim, Y. G.; Li, L.; Brown, B. A. 2nd; Herbert, A.; Rich, A.

    1999-01-01

    Zalpha is a peptide motif that binds to Z-DNA with high affinity. This motif binds to alternating dC-dG sequences stabilized in the Z-conformation by means of bromination or supercoiling, but not to B-DNA. Zalpha is part of the N-terminal region of double-stranded RNA adenosine deaminase (ADAR1), a candidate enzyme for nuclear pre-mRNA editing in mammals. Zalpha is conserved in ADAR1 from many species; in each case, there is a second similar motif, Zbeta, separated from Zalpha by a more divergent linker. To investigate the structure-function relationship of Zalpha, its domain structure was studied by limited proteolysis. Proteolytic profiles indicated that Zalpha is part of a domain, Zab, of 229 amino acids (residues 133-361 in human ADAR1). This domain contains both Zalpha and Zbeta as well as a tandem repeat of a 49-amino acid linker module. Prolonged proteolysis revealed a minimal core domain of 77 amino acids (positions 133-209), containing only Zalpha, which is sufficient to bind left-handed Z-DNA; however, the substrate binding is strikingly different from that of Zab. The second motif, Zbeta, retains its structural integrity only in the context of Zab and does not bind Z-DNA as a separate entity. These results suggest that Zalpha and Zbeta act as a single bipartite domain. In the presence of substrate DNA, Zab becomes more resistant to proteases, suggesting that it adopts a more rigid structure when bound to its substrate, possibly with conformational changes in parts of the protein.

  1. Antiferromagnetic domain wall as spin wave polarizer and retarder.

    PubMed

    Lan, Jin; Yu, Weichao; Xiao, Jiang

    2017-08-02

    As a collective quasiparticle excitation of the magnetic order in magnetic materials, spin wave, or magnon when quantized, can propagate in both conducting and insulating materials. Like the manipulation of its optical counterpart, the ability to manipulate spin wave polarization is not only important but also fundamental for magnonics. With only one type of magnetic lattice, ferromagnets can only accommodate the right-handed circularly polarized spin wave modes, which leaves no freedom for polarization manipulation. In contrast, antiferromagnets, with two opposite magnetic sublattices, have both left and right-circular polarizations, and all linear and elliptical polarizations. Here we demonstrate theoretically and confirm by micromagnetic simulations that, in the presence of Dzyaloshinskii-Moriya interaction, an antiferromagnetic domain wall acts naturally as a spin wave polarizer or a spin wave retarder (waveplate). Our findings provide extremely simple yet flexible routes toward magnonic information processing by harnessing the polarization degree of freedom of spin wave.Spin waves are promising candidates as carriers for energy-efficient information processing, but they have not yet been fully explored application wise. Here the authors theoretically demonstrate that antiferromagnetic domain walls are naturally spin wave polarizers and retarders, two key components of magnonic devices.

  2. Spin-orbit-torque-induced magnetic domain wall motion in Ta/CoFe nanowires with sloped perpendicular magnetic anisotropy.

    PubMed

    Zhang, Yue; Luo, Shijiang; Yang, Xiaofei; Yang, Chang

    2017-05-17

    In materials with the gradient of magnetic anisotropy, spin-orbit-torque-induced magnetization behaviour has attracted attention because of its intriguing scientific principle and potential application. Most of the magnetization behaviours microscopically originate from magnetic domain wall motion, which can be precisely depicted using the standard cooperative coordinate method (CCM). However, the domain wall motion in materials with the gradient of magnetic anisotropy using the CCM remains lack of investigation. In this paper, by adopting CCM, we established a set of equations to quantitatively depict the spin-orbit-torque-induced motion of domain walls in a Ta/CoFe nanotrack with weak Dzyaloshinskii-Moriya interaction and magnetic anisotropy gradient. The equations were solved numerically, and the solutions are similar to those of a micromagnetic simulation. The results indicate that the enhanced anisotropy along the track acts as a barrier to inhibit the motion of the domain wall. In contrast, the domain wall can be pushed to move in a direction with reduced anisotropy, with the velocity being accelerated by more than twice compared with that for the constant anisotropy case. This substantial velocity manipulation by anisotropy engineering is important in designing novel magnetic information devices with high reading speeds.

  3. Control of domain wall pinning by localised focused Ga {sup +} ion irradiation on Au capped NiFe nanowires

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

    Burn, D. M., E-mail: d.burn@imperial.ac.uk; Atkinson, D.

    2014-10-28

    Understanding domain wall pinning and propagation in nanowires are important for future spintronics and nanoparticle manipulation technologies. Here, the effects of microscopic local modification of the magnetic properties, induced by focused-ion-beam intermixing, in NiFe/Au bilayer nanowires on the pinning behavior of domain walls was investigated. The effects of irradiation dose and the length of the irradiated features were investigated experimentally. The results are considered in the context of detailed quasi-static micromagnetic simulations, where the ion-induced modification was represented as a local reduction of the saturation magnetization. Simulations show that domain wall pinning behavior depends on the magnitude of the magnetizationmore » change, the length of the modified region, and the domain wall structure. Comparative analysis indicates that reduced saturation magnetisation is not solely responsible for the experimentally observed pinning behavior.« less

  4. Topological Luttinger liquids from decorated domain walls

    NASA Astrophysics Data System (ADS)

    Parker, Daniel E.; Scaffidi, Thomas; Vasseur, Romain

    2018-04-01

    We introduce a systematic construction of a gapless symmetry-protected topological phase in one dimension by "decorating" the domain walls of Luttinger liquids. The resulting strongly interacting phases provide a concrete example of a gapless symmetry-protected topological (gSPT) phase with robust symmetry-protected edge modes. Using boundary conformal field theory arguments, we show that while the bulks of such gSPT phases are identical to conventional Luttinger liquids, their boundary critical behavior is controlled by a different, strongly coupled renormalization group fixed point. Our results are checked against extensive density matrix renormalization group calculations.

  5. Two zinc-binding domains in the transporter AdcA from Streptococcus pyogenes facilitate high-affinity binding and fast transport of zinc.

    PubMed

    Cao, Kun; Li, Nan; Wang, Hongcui; Cao, Xin; He, Jiaojiao; Zhang, Bing; He, Qing-Yu; Zhang, Gong; Sun, Xuesong

    2018-04-20

    Zinc is an essential metal in bacteria. One important bacterial zinc transporter is AdcA, and most bacteria possess AdcA homologs that are single-domain small proteins due to better efficiency of protein biogenesis. However, a double-domain AdcA with two zinc-binding sites is significantly overrepresented in Streptococcus species, many of which are major human pathogens. Using molecular simulation and experimental validations of AdcA from Streptococcus pyogenes , we found here that the two AdcA domains sequentially stabilize the structure upon zinc binding, indicating an organization required for both increased zinc affinity and transfer speed. This structural organization appears to endow Streptococcus species with distinct advantages in zinc-depleted environments, which would not be achieved by each single AdcA domain alone. This enhanced zinc transport mechanism sheds light on the significance of the evolution of the AdcA domain fusion, provides new insights into double-domain transporter proteins with two binding sites for the same ion, and indicates a potential target of antimicrobial drugs against pathogenic Streptococcus species. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Bianchi type-I domain walls with negative constant deceleration parameter in Brans-Dicke theory

    NASA Astrophysics Data System (ADS)

    Katore, S. D.

    2011-04-01

    Bianchi type-I space-time is considered in the presence of a domain walls source in the scalar-tensor theory of gravitation proposed by Brans and Dicke (C.H. Brans and R.H. Dicke, Phys. Rev. 24, 925 (1961)). With the help of the special law of variation for Hubble's parameter proposed by Bermann (M.S. Berman, Nuovo Cimento B 74, 182 (1983)) a cosmological model with negative constant deceleration parameter is obtained in the presence of domain walls. Some physical properties of the model are also discussed.

  7. FRET-based binding assay between a fluorescent cAMP analogue and a cyclic nucleotide-binding domain tagged with a CFP.

    PubMed

    Romero, Francisco; Santana-Calvo, Carmen; Sánchez-Guevara, Yoloxochitl; Nishigaki, Takuya

    2017-09-01

    The cyclic nucleotide-binding domain (CNBD) functions as a regulatory domain of many proteins involved in cyclic nucleotide signalling. We developed a straightforward and reliable binding assay based on intermolecular fluorescence resonance energy transfer (FRET) between an adenosine-3', 5'-cyclic monophosphate analogue labelled with fluorescein and a recombinant CNBD of human EPAC1 tagged with a cyan fluorescence protein (CFP). The high FRET efficiency of this method (~ 80%) allowed us to perform several types of binding experiments with nanomolar range of sample using conventional equipment. In addition, the CFP tag on the CNBD enabled us to perform a specific binding experiment using an unpurified protein. Considering these advantages, this technique is useful to study poorly characterized CNBDs. © 2017 Federation of European Biochemical Societies.

  8. The chitin-binding domain of a GH-18 chitinase from Vibrio harveyi is crucial for chitin-chitinase interactions.

    PubMed

    Suginta, Wipa; Sirimontree, Paknisa; Sritho, Natchanok; Ohnuma, Takayuki; Fukamizo, Tamo

    2016-12-01

    Vibrio harveyi chitinase A (VhChiA) is a GH-18 glycosyl hydrolase with a structure containing three distinct domains: i) the N-terminal chitin-binding domain; ii) the (α/β) 8 TIM barrel catalytic domain; and iii) the α+β insertion domain. In this study, we cloned the gene fragment encoding the chitin-binding domain of VhChiA, termed ChBD Vh ChiA . The recombinant ChBD Vh ChiA was heterologously expressed in E. coli BL21 strain Tuner(DE3)pLacI host cells, and purified to homogeneity. CD measurements suggested that ChBD Vh ChiA contained β-sheets as major structural components and fluorescence spectroscopy showed that the protein domain was folded correctly, and suitable for functional characterization. Chitin binding assays showed that ChBD Vh ChiA bound to both α- and β-chitins, with the greatest affinity for β-colloidal chitin, but barely bound to polymeric chitosan. These results identified the tandem N-acetamido functionality on chitin chains as the specific sites of enzyme-substrate interactions. The binding affinity of the isolated domain was significantly lower than that of intact VhChiA, suggesting that the catalytic domain works synergistically with the chitin-binding domain to guide the polymeric substrate into the substrate binding cleft. These data confirm the physiological role of the chitin-binding domain of the marine bacterial GH-18 chitinase A in chitin-chitinase interactions. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Distinct peptide binding specificities of Src homology 3 (SH3) protein domains can be determined by modulation of local energetics across the binding interface.

    PubMed

    Gorelik, Maryna; Davidson, Alan R

    2012-03-16

    The yeast Nbp2p SH3 and Bem1p SH3b domains bind certain target peptides with similar high affinities, yet display vastly different affinities for other targets. To investigate this unusual behavior, we have solved the structure of the Nbp2p SH3-Ste20 peptide complex and compared it with the previously determined structure of the Bem1p SH3b bound to the same peptide. Although the Ste20 peptide interacts with both domains in a structurally similar manner, extensive in vitro studies with domain and peptide mutants revealed large variations in interaction strength across the binding interface of the two complexes. Whereas the Nbp2p SH3 made stronger contacts with the peptide core RXXPXXP motif, the Bem1p SH3b domain made stronger contacts with residues flanking the core motif. Remarkably, this modulation of local binding energetics can explain the distinct and highly nuanced binding specificities of these two domains.

  10. Ubiquitin Regulates Caspase Recruitment Domain-mediated Signaling by Nucleotide-binding Oligomerization Domain-containing Proteins NOD1 and NOD2*

    PubMed Central

    Ver Heul, Aaron M.; Fowler, C. Andrew; Ramaswamy, S.; Piper, Robert C.

    2013-01-01

    NOD1 and NOD2 (nucleotide-binding oligomerization domain-containing proteins) are intracellular pattern recognition receptors that activate inflammation and autophagy. These pathways rely on the caspase recruitment domains (CARDs) within the receptors, which serve as protein interaction platforms that coordinately regulate immune signaling. We show that NOD1 CARD binds ubiquitin (Ub), in addition to directly binding its downstream targets receptor-interacting protein kinase 2 (RIP2) and autophagy-related protein 16-1 (ATG16L1). NMR spectroscopy and structure-guided mutagenesis identified a small hydrophobic surface of NOD1 CARD that binds Ub. In vitro, Ub competes with RIP2 for association with NOD1 CARD. In vivo, we found that the ligand-stimulated activity of NOD1 with a mutant CARD lacking Ub binding but retaining ATG16L1 and RIP2 binding is increased relative to wild-type NOD1. Likewise, point mutations in the tandem NOD2 CARDs at positions analogous to the surface residues defining the Ub interface on NOD1 resulted in loss of Ub binding and increased ligand-stimulated NOD2 signaling. These data suggest that Ub binding provides a negative feedback loop upon NOD-dependent activation of RIP2. PMID:23300079

  11. Structure of the E2 DNA-binding domain from human papillomavirus serotype 31 at 2.4 A.

    PubMed

    Bussiere, D E; Kong, X; Egan, D A; Walter, K; Holzman, T F; Lindh, F; Robins, T; Giranda, V L

    1998-11-01

    The papillomaviruses are a family of small double-stranded DNA viruses which exclusively infect epithelial cells and stimulate the proliferation of those cells. A key protein within the papillomavirus life-cycle is known as the E2 (Early 2) protein and is responsible for regulating viral transcription from all viral promoters as well as for replication of the papillomavirus genome in tandem with another protein known as E1. The E2 protein itself consists of three functional domains: an N-terminal trans-activation domain, a proline-rich linker, and a C-terminal DNA-binding domain. The first crystal structure of the human papillomavirus, serotype 31 (HPV-31), E2 DNA-binding domain has been determined at 2.4 A resolution. The HPV DNA-binding domain monomer consists of two beta-alpha-beta repeats of approximately equal length and is arranged as to have an anti-parallel beta-sheet flanked by the two alpha-helices. The monomers form the functional in vivo dimer by association of the beta-sheets of each monomer so as to form an eight-stranded anti-parallel beta-barrel at the center of the dimer, with the alpha-helices lining the outside of the barrel. The overall structure of HVP-31 E2 DNA-binding domain is similar to both the bovine papillomavirus E2-binding domain and the Epstein-Barr nuclear antigen-1 DNA-binding domain.

  12. A gain-of-function mutation in the M-domain of cardiac myosin-binding protein-C increases binding to actin.

    PubMed

    Bezold, Kristina L; Shaffer, Justin F; Khosa, Jaskiran K; Hoye, Elaine R; Harris, Samantha P

    2013-07-26

    The M-domain is the major regulatory subunit of cardiac myosin-binding protein-C (cMyBP-C) that modulates actin and myosin interactions to influence muscle contraction. However, the precise mechanism(s) and the specific residues involved in mediating the functional effects of the M-domain are not fully understood. Positively charged residues adjacent to phosphorylation sites in the M-domain are thought to be critical for effects of cMyBP-C on cross-bridge interactions by mediating electrostatic binding with myosin S2 and/or actin. However, recent structural studies revealed that highly conserved sequences downstream of the phosphorylation sites form a compact tri-helix bundle. Here we used site-directed mutagenesis to probe the functional significance of charged residues adjacent to the phosphorylation sites and conserved residues within the tri-helix bundle. Results confirm that charged residues adjacent to phosphorylation sites and residues within the tri-helix bundle are important for mediating effects of the M-domain on contraction. In addition, four missense variants within the tri-helix bundle that are associated with human hypertrophic cardiomyopathy caused either loss-of-function or gain-of-function effects on force. Importantly, the effects of the gain-of-function variant, L348P, increased the affinity of the M-domain for actin. Together, results demonstrate that functional effects of the M-domain are not due solely to interactions with charged residues near phosphorylatable serines and provide the first demonstration that the tri-helix bundle contributes to the functional effects of the M-domain, most likely by binding to actin.

  13. PDZ Binding Domains, Structural Disorder and Phosphorylation: A Menage-a-trois Tailing Dcp2 mRNA Decapping Enzymes.

    PubMed

    Gunawardana, Dilantha

    2016-01-01

    Diverse cellular activities are mediated through the interaction of protein domains and their binding partners. One such protein domain widely distributed in the higher metazoan world is the PDZ domain, which facilitates abundant protein-protein interactions. The PDZ domain-PDZ binding domain interaction has been implicated in several pathologies including Alzheimer's disease, Parkinson's disease and Down syndrome. PDZ domains bind to C-terminal peptides/proteins which have either of the following combinations: S/T-X-hydrophobic-COOH for type I, hydrophobic-Xhydrophobic- COOH for type II, and D/E-X-hydrophobic-COOH for type III, although hydrophobicity in the termini form the key characteristic of the PDZ-binding domains. We identified and characterized a Dcp2 type mRNA decapping enzyme from Arabidopsis thaliana, a protein containing a putative PDZ-binding domain using mutagenesis and protein biochemistry. Now we are using bioinformatics to study the Cterminal end of mRNA decapping enzymes from complex metazoans with the aim of (1) identifying putative PDZ-binding domains (2) Correlating structural disorder with PDZ binding domains and (3) Demonstrating the presence of phosphorylation sites in C-terminal extremities of Dcp2 type mRNA decapping enzymes. It is proposed here that the trinity of PDZbinding domains, structural disorder and phosphorylation-susceptible sites are a feature of the Dcp2 family of decapping enzymes and perhaps is a wider trick in protein evolution where scaffolding/tethering is a requirement for localization and function. It is critical though laboratory-based supporting evidence is sought to back-up this bioinformatics exploration into tail regions of mRNA decapping enzymes.

  14. PDZ binding to the BAR domain of PICK1 is elucidated by coarse-grained molecular dynamics.

    PubMed

    He, Yi; Liwo, Adam; Weinstein, Harel; Scheraga, Harold A

    2011-01-07

    A key regulator of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor traffic, PICK1 is known to interact with over 40 other proteins, including receptors, transporters and ionic channels, and to be active mostly as a homodimer. The current lack of a complete PICK1 structure determined at atomic resolution hinders the elucidation of its functional mechanisms. Here, we identify interactions between the component PDZ and BAR domains of PICK1 by calculating possible binding sites for the PDZ domain of PICK1 (PICK1-PDZ) to the homology-modeled, crescent-shaped dimer of the PICK1-BAR domain using multiplexed replica-exchange molecular dynamics (MREMD) and canonical molecular dynamics simulations with the coarse-grained UNRES force field. The MREMD results show that the preferred binding site for the single PDZ domain is the concave cavity of the BAR dimer. A second possible binding site is near the N-terminus of the BAR domain that is linked directly to the PDZ domain. Subsequent short canonical molecular dynamics simulations used to determine how the PICK1-PDZ domain moves to the preferred binding site on the BAR domain of PICK1 revealed that initial hydrophobic interactions drive the progress of the simulated binding. Thus, the concave face of the BAR dimer accommodates the PDZ domain first by weak hydrophobic interactions and then the PDZ domain slides to the center of the concave face, where more favorable hydrophobic interactions take over. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Correlation between the viscoelastic heterogeneity and the domain wall motion of Fe-based metallic glass

    NASA Astrophysics Data System (ADS)

    Ouyang, S.; Song, L. J.; Liu, Y. H.; Huo, J. T.; Wang, J. Q.; Xu, W.; Li, J. L.; Wang, C. T.; Wang, X. M.; Li, R. W.

    2018-06-01

    The soft magnetic properties of Fe-based metallic glasses are reduced significantly by external and residual stresses, e.g., the susceptibility decreases and coercivity increases, which limits their application severely. Unraveling the micromechanism of how the stress influences the soft magnetic properties is of great help for enhancing the performance of Fe-based metallic glasses. In this work, we investigate the effect of viscoelastic heterogeneity on the motion of magnetic domain wall surrounding nanoindentations. Compared to the matrix, dissipation of the viscoelastic heterogeneity increases toward the nanoindentation. Meanwhile, the motion of domain wall under external magnetic field becomes more difficult toward the nanoindentations. A correlation between the viscoelastic dissipation and the moving ability of magnetic domain walls is observed, which can be well fitted using magnetoelastic coupling theory. This suggests that manipulating the microscale viscoelastic heterogeneity is probably a helpful strategy for enhancing the soft magnetic properties of metallic glasses.

  16. FAST TRACK COMMUNICATION Critical exponents of domain walls in the two-dimensional Potts model

    NASA Astrophysics Data System (ADS)

    Dubail, Jérôme; Lykke Jacobsen, Jesper; Saleur, Hubert

    2010-12-01

    We address the geometrical critical behavior of the two-dimensional Q-state Potts model in terms of the spin clusters (i.e. connected domains where the spin takes a constant value). These clusters are different from the usual Fortuin-Kasteleyn clusters, and are separated by domain walls that can cross and branch. We develop a transfer matrix technique enabling the formulation and numerical study of spin clusters even when Q is not an integer. We further identify geometrically the crossing events which give rise to conformal correlation functions. This leads to an infinite series of fundamental critical exponents h_{\\ell _1-\\ell _2,2\\ell _1}, valid for 0 <= Q <= 4, that describe the insertion of ell1 thin and ell2 thick domain walls.

  17. Trapping and Injecting Single Domain Walls in Magnetic Wire by Local Fields

    NASA Astrophysics Data System (ADS)

    Vázquez, Manuel; Basheed, G. A.; Infante, Germán; Del Real, Rafael P.

    2012-01-01

    A single domain wall (DW) moves at linearly increasing velocity under an increasing homogeneous drive magnetic field. Present experiments show that the DW is braked and finally trapped at a given position when an additional antiparallel local magnetic field is applied. That position and its velocity are further controlled by suitable tuning of the local field. In turn, the parallel local field of small amplitude does not significantly affect the effective wall speed at long distance, although it generates tail-to-tail and head-to-head pairs of walls moving along opposite directions when that field is strong enough.

  18. Strain-controlled magnetic domain wall propagation in hybrid piezoelectric/ferromagnetic structures

    PubMed Central

    Lei, Na; Devolder, Thibaut; Agnus, Guillaume; Aubert, Pascal; Daniel, Laurent; Kim, Joo-Von; Zhao, Weisheng; Trypiniotis, Theodossis; Cowburn, Russell P.; Chappert, Claude; Ravelosona, Dafiné; Lecoeur, Philippe

    2013-01-01

    The control of magnetic order in nanoscale devices underpins many proposals for integrating spintronics concepts into conventional electronics. A key challenge lies in finding an energy-efficient means of control, as power dissipation remains an important factor limiting future miniaturization of integrated circuits. One promising approach involves magnetoelectric coupling in magnetostrictive/piezoelectric systems, where induced strains can bear directly on the magnetic anisotropy. While such processes have been demonstrated in several multiferroic heterostructures, the incorporation of such complex materials into practical geometries has been lacking. Here we demonstrate the possibility of generating sizeable anisotropy changes, through induced strains driven by applied electric fields, in hybrid piezoelectric/spin-valve nanowires. By combining magneto-optical Kerr effect and magnetoresistance measurements, we show that domain wall propagation fields can be doubled under locally applied strains. These results highlight the prospect of constructing low-power domain wall gates for magnetic logic devices. PMID:23340418

  19. Indirect Coupling of Magnetic Layers via Domain Wall Fringing fields

    NASA Astrophysics Data System (ADS)

    Parkin, Stuart

    2001-03-01

    Ferromagnetic films separated by thin metallic spacer layers are usually coupled through an indirect exchange interaction which oscillates in sign between ferro and antiferromagnetic coupling as a function of the spacer layer thickness^1. For both such metallic systems, and for multilayered systems in which the ferromagnetic films are separated by thin insulating layers, correlated roughness of the magnetic layers gives rise to a weak ferromagnetic coupling via dipole fields. Another type of dipolar coupling mechanism, which has largely been ignored, is that arising from domain wall fringing fields. These fields can be locally very large^2 and can result in the demagnetization of ferromagnetic films which are nominally highly coercive ("hard") in sandwiches comprised of "hard" and "soft" ferromagnetic layers. When the moment of the soft layer is reversed back and forth in small magnetic fields, much too small to affect the moment of the hard layer, substantial local fringing fields from domain walls created in the soft film gradually result in the demagnetization of the hard film. In some cases the moment of the hard layer decays in an oscillatory manner as it is successively partially demagnetized and remagnetized. This process has been observed on both macroscopic and microscopic length scales using SQUID magnetometry and high resolution photoemission electron microscopy, respectively^3. Magnetic interactions from domain wall fringing fields may be very important for magnetic devices, especially, magnetoresistance sensors and memory elements. [1] S.S.P. Parkin, N. More and K.P. Roche, Phys. Rev. Lett. 64, 2304 (1990); S.S.P. Parkin, Phys. Rev. Lett., 67, 3598 (1991). [2] L. Thomas, M. Samant and S.S.P. Parkin, Phys. Rev. Lett. 84, 1816 (2000). [3] L. Thomas, J Lüning, A. Scholl, F. Nolting, S. Anders, J. Stöhr and S.S.P. Parkin, Phys. Rev. Lett. 84, 3462 (2000).

  20. Isospin Breaking Corrections to the HVP with Domain Wall Fermions

    NASA Astrophysics Data System (ADS)

    Boyle, Peter; Guelpers, Vera; Harrison, James; Juettner, Andreas; Lehner, Christoph; Portelli, Antonin; Sachrajda, Christopher

    2018-03-01

    We present results for the QED and strong isospin breaking corrections to the hadronic vacuum polarization using Nf = 2 + 1 Domain Wall fermions. QED is included in an electro-quenched setup using two different methods, a stochastic and a perturbative approach. Results and statistical errors from both methods are directly compared with each other.

  1. Sequence Discrimination by Alternatively Spliced Isoforms of a DNA Binding Zinc Finger Domain

    NASA Astrophysics Data System (ADS)

    Gogos, Joseph A.; Hsu, Tien; Bolton, Jesse; Kafatos, Fotis C.

    1992-09-01

    Two major developmentally regulated isoforms of the Drosophila chorion transcription factor CF2 differ by an extra zinc finger within the DNA binding domain. The preferred DNA binding sites were determined and are distinguished by an internal duplication of TAT in the site recognized by the isoform with the extra finger. The results are consistent with modular interactions between zinc fingers and trinucleotides and also suggest rules for recognition of AT-rich DNA sites by zinc finger proteins. The results show how modular finger interactions with trinucleotides can be used, in conjunction with alternative splicing, to alter the binding specificity and increase the spectrum of sites recognized by a DNA binding domain. Thus, CF2 may potentially regulate distinct sets of target genes during development.

  2. Using peptide array to identify binding motifs and interaction networks for modular domains.

    PubMed

    Li, Shawn S-C; Wu, Chenggang

    2009-01-01

    Specific protein-protein interactions underlie all essential biological processes and form the basis of cellular signal transduction. The recognition of a short, linear peptide sequence in one protein by a modular domain in another represents a common theme of macromolecular recognition in cells, and the importance of this mode of protein-protein interaction is highlighted by the large number of peptide-binding domains encoded by the human genome. This phenomenon also provides a unique opportunity to identify protein-protein binding events using peptide arrays and complementary biochemical assays. Accordingly, high-density peptide array has emerged as a useful tool by which to map domain-mediated protein-protein interaction networks at the proteome level. Using the Src-homology 2 (SH2) and 3 (SH3) domains as examples, we describe the application of oriented peptide array libraries in uncovering specific motifs recognized by an SH2 domain and the use of high-density peptide arrays in identifying interaction networks mediated by the SH3 domain. Methods reviewed here could also be applied to other modular domains, including catalytic domains, that recognize linear peptide sequences.

  3. Bacterial SPOR domains are recruited to septal peptidoglycan by binding to glycan strands that lack stem peptides

    PubMed Central

    Yahashiri, Atsushi; Jorgenson, Matthew A.; Weiss, David S.

    2015-01-01

    Bacterial SPOR domains bind peptidoglycan (PG) and are thought to target proteins to the cell division site by binding to “denuded” glycan strands that lack stem peptides, but uncertainties remain, in part because septal-specific binding has yet to be studied in a purified system. Here we show that fusions of GFP to SPOR domains from the Escherichia coli cell-division proteins DamX, DedD, FtsN, and RlpA all localize to septal regions of purified PG sacculi obtained from E. coli and Bacillus subtilis. Treatment of sacculi with an amidase that removes stem peptides enhanced SPOR domain binding, whereas treatment with a lytic transglycosylase that removes denuded glycans reduced SPOR domain binding. These findings demonstrate unequivocally that SPOR domains localize by binding to septal PG, that the physiologically relevant binding site is indeed a denuded glycan, and that denuded glycans are enriched in septal PG rather than distributed uniformly around the sacculus. Accumulation of denuded glycans in the septal PG of both E. coli and B. subtilis, organisms separated by 1 billion years of evolution, suggests that sequential removal of stem peptides followed by degradation of the glycan backbone is an ancient feature of PG turnover during bacterial cell division. Linking SPOR domain localization to the abundance of a structure (denuded glycans) present only transiently during biogenesis of septal PG provides a mechanism for coordinating the function of SPOR domain proteins with the progress of cell division. PMID:26305949

  4. Ubiquitin Interacts with the Tollip C2 and CUE Domains and Inhibits Binding of Tollip to Phosphoinositides*

    PubMed Central

    Mitra, Sharmistha; Traughber, C. Alicia; Brannon, Mary K.; Gomez, Stephanie; Capelluto, Daniel G. S.

    2013-01-01

    A large number of cellular signaling processes are directed through internalization, via endocytosis, of polyubiquitinated cargo proteins. Tollip is an adaptor protein that facilitates endosomal cargo sorting for lysosomal degradation. Tollip preferentially binds phosphatidylinositol 3-phosphate (PtdIns(3)P) via its C2 domain, an association that may be required for endosomal membrane targeting. Here, we show that Tollip binds ubiquitin through its C2 and CUE domains and that its association with the C2 domain inhibits PtdIns(3)P binding. NMR analysis demonstrates that the C2 and CUE domains bind to overlapping sites on ubiquitin, suggesting that two ubiquitin molecules associate with Tollip simultaneously. Hydrodynamic studies reveal that ubiquitin forms heterodimers with the CUE domain, indicating that the association disrupts the dimeric state of the CUE domain. We propose that, in the absence of polyubiquitinated cargo, the dual binding of ubiquitin partitions Tollip into membrane-bound and membrane-free states, a function that contributes to the engagement of Tollip in both membrane trafficking and cytosolic pathways. PMID:23880770

  5. The Rapamycin-Binding Domain of the Protein Kinase mTOR is a Destabilizing Domain*

    PubMed Central

    Edwards, Sarah R.; Wandless, Thomas J.

    2013-01-01

    Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding domain (FRB) of the mammalian target of rapamycin (mTOR) kinase. The resulting ternary complex has been used to conditionally perturb protein function, and one such method involves perturbation of a protein of interest through its mislocalization. We synthesized two rapamycin derivatives that possess large substituents at the C16 position within the FRB-binding interface, and these derivatives were screened against a library of FRB mutants using a three-hybrid assay in Saccharomyces cerevisiae. Several FRB mutants responded to one of the rapamycin derivatives, and twenty of these mutants were further characterized in mammalian cells. The mutants most responsive to the ligand were fused to yellow fluorescent protein, and fluorescence levels in the presence and absence of the ligand were measured to determine stability of the fusion proteins. Wild-type and mutant FRB domains were expressed at low levels in the absence of the rapamycin derivative, and expression levels rose up to ten-fold upon treatment with ligand. The synthetic rapamycin derivatives were further analyzed using quantitative mass spectrometry, and one of the compounds was found to contain contaminating rapamycin. Furthermore, uncontaminated analogs retain the ability to inhibit mTOR, albeit with diminished potency relative to rapamycin. The ligand-dependent stability displayed by wildtype FRB and FRB mutants as well as the inhibitory potential and purity of the rapamycin derivatives should be considered as potentially confounding experimental variables when using these systems. PMID:17350953

  6. G-structures and domain walls in heterotic theories

    NASA Astrophysics Data System (ADS)

    Lukas, Andre; Matti, Cyril

    2011-01-01

    We consider heterotic string solutions based on a warped product of a four-dimensional domain wall and a six-dimensional internal manifold, preserving two supercharges. The constraints on the internal manifolds with SU(3) structure are derived. They are found to be generalized half-flat manifolds with a particular pattern of torsion classes and they include half-flat manifolds and Strominger's complex non-Kahler manifolds as special cases. We also verify that previous heterotic compactifications on half-flat mirror manifolds are based on this class of solutions.

  7. Tunneling decay of false domain walls: The silence of the lambs

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

    Haberichter, Mareike, E-mail: M.Haberichter@kent.ac.uk; School of Mathematics, Statistics and Actuarial Science, University of Kent, Canterbury CT2 7NF; MacKenzie, Richard, E-mail: richard.mackenzie@umontreal.ca

    We study the decay of “false” domain walls, that is, metastable states of the quantum theory where the true vacuum is trapped inside the wall with the false vacuum outside. We consider a theory with two scalar fields, a shepherd field and a field of sheep. The shepherd field serves to herd the solitons of the sheep field so that they are nicely bunched together. However, quantum tunnelling of the shepherd field releases the sheep to spread out uncontrollably. We show how to calculate the tunnelling amplitude for such a disintegration.

  8. Aurora A regulates the activity of HURP by controlling the accessibility of its microtubule-binding domain.

    PubMed

    Wong, Jim; Lerrigo, Robert; Jang, Chang-Young; Fang, Guowei

    2008-05-01

    HURP is a spindle-associated protein that mediates Ran-GTP-dependent assembly of the bipolar spindle and promotes chromosome congression and interkinetochore tension during mitosis. We report here a biochemical mechanism of HURP regulation by Aurora A, a key mitotic kinase that controls the assembly and function of the spindle. We found that HURP binds to microtubules through its N-terminal domain that hyperstabilizes spindle microtubules. Ectopic expression of this domain generates defects in spindle morphology and function that reduce the level of tension across sister kinetochores and activate the spindle checkpoint. Interestingly, the microtubule binding activity of this N-terminal domain is regulated by the C-terminal region of HURP: in its hypophosphorylated state, C-terminal HURP associates with the microtubule-binding domain, abrogating its affinity for microtubules. However, when the C-terminal domain is phosphorylated by Aurora A, it no longer binds to N-terminal HURP, thereby releasing the inhibition on its microtubule binding and stabilizing activity. In fact, ectopic expression of this C-terminal domain depletes endogenous HURP from the mitotic spindle in HeLa cells in trans, suggesting the physiological importance for this mode of regulation. We concluded that phosphorylation of HURP by Aurora A provides a regulatory mechanism for the control of spindle assembly and function.

  9. Transmission XMCD-PEEM imaging of an engineered vertical FEBID cobalt nanowire with a domain wall

    NASA Astrophysics Data System (ADS)

    Wartelle, A.; Pablo-Navarro, J.; Staňo, M.; Bochmann, S.; Pairis, S.; Rioult, M.; Thirion, C.; Belkhou, R.; de Teresa, J. M.; Magén, C.; Fruchart, O.

    2018-01-01

    Using focused electron-beam-induced deposition, we fabricate a vertical, platinum-coated cobalt nanowire with a controlled three-dimensional structure. The latter is engineered to feature bends along the height: these are used as pinning sites for domain walls, which are obtained at remanence after saturation of the nanostructure in a horizontally applied magnetic field. The presence of domain walls is investigated using x-ray magnetic circular dichroism (XMCD) coupled to photoemission electron microscopy (PEEM). The vertical geometry of our sample combined with the low incidence of the x-ray beam produce an extended wire shadow which we use to recover the wire’s magnetic configuration. In this transmission configuration, the whole sample volume is probed, thus circumventing the limitation of PEEM to surfaces. This article reports on the first study of magnetic nanostructures standing perpendicular to the substrate with XMCD-PEEM. The use of this technique in shadow mode enabled us to confirm the presence of a domain wall without direct imaging of the nanowire.

  10. Plasticity of BRCA2 Function in Homologous Recombination: Genetic Interactions of the PALB2 and DNA Binding Domains

    PubMed Central

    Siaud, Nicolas; Lam, Isabel; Christ, Nicole; Schlacher, Katharina; Xia, Bing; Jasin, Maria

    2011-01-01

    The breast cancer suppressor BRCA2 is essential for the maintenance of genomic integrity in mammalian cells through its role in DNA repair by homologous recombination (HR). Human BRCA2 is 3,418 amino acids and is comprised of multiple domains that interact with the RAD51 recombinase and other proteins as well as with DNA. To gain insight into the cellular function of BRCA2 in HR, we created fusions consisting of various BRCA2 domains and also introduced mutations into these domains to disrupt specific protein and DNA interactions. We find that a BRCA2 fusion peptide deleted for the DNA binding domain and active in HR is completely dependent on interaction with the PALB2 tumor suppressor for activity. Conversely, a BRCA2 fusion peptide deleted for the PALB2 binding domain is dependent on an intact DNA binding domain, providing a role for this conserved domain in vivo; mutagenesis suggests that both single-stranded and double-stranded DNA binding activities in the DNA binding domain are required for its activity. Given that PALB2 itself binds DNA, these results suggest alternative mechanisms to deliver RAD51 to DNA. In addition, the BRCA2 C terminus contains both RAD51-dependent and -independent activities which are essential to HR in some contexts. Finally, binding the small peptide DSS1 is essential for activity when its binding domain is present, but not when it is absent. Our results reveal functional redundancy within the BRCA2 protein and emphasize the plasticity of this large protein built for optimal HR function in mammalian cells. The occurrence of disease-causing mutations throughout BRCA2 suggests sub-optimal HR from a variety of domain modulations. PMID:22194698

  11. Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain.

    PubMed

    Bottomley, Matthew J; Lo Surdo, Paola; Di Giovine, Paolo; Cirillo, Agostino; Scarpelli, Rita; Ferrigno, Federica; Jones, Philip; Neddermann, Petra; De Francesco, Raffaele; Steinkühler, Christian; Gallinari, Paola; Carfí, Andrea

    2008-09-26

    Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR.HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions.

  12. Logic circuit prototypes for three-terminal magnetic tunnel junctions with mobile domain walls

    PubMed Central

    Currivan-Incorvia, J. A.; Siddiqui, S.; Dutta, S.; Evarts, E. R.; Zhang, J.; Bono, D.; Ross, C. A.; Baldo, M. A.

    2016-01-01

    Spintronic computing promises superior energy efficiency and nonvolatility compared to conventional field-effect transistor logic. But, it has proven difficult to realize spintronic circuits with a versatile, scalable device design that is adaptable to emerging material physics. Here we present prototypes of a logic device that encode information in the position of a magnetic domain wall in a ferromagnetic wire. We show that a single three-terminal device can perform inverter and buffer operations. We demonstrate one device can drive two subsequent gates and logic propagation in a circuit of three inverters. This prototype demonstration shows that magnetic domain wall logic devices have the necessary characteristics for future computing, including nonlinearity, gain, cascadability, and room temperature operation. PMID:26754412

  13. A novel signal transduction protein: Combination of solute binding and tandem PAS-like sensor domains in one polypeptide chain: Periplasmic Ligand Binding Protein Dret_0059

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

    Wu, R.; Wilton, R.; Cuff, M. E.

    We report the structural and biochemical characterization of a novel periplasmic ligand-binding protein, Dret_0059, from Desulfohalobium retbaense DSM 5692, an organism isolated from the Salt Lake Retba in Senegal. The structure of the protein consists of a unique combination of a periplasmic solute binding protein (SBP) domain at the N-terminal and a tandem PAS-like sensor domain at the C-terminal region. SBP domains are found ubiquitously and their best known function is in solute transport across membranes. PAS-like sensor domains are commonly found in signal transduction proteins. These domains are widely observed as parts of many protein architectures and complexes butmore » have not been observed previously within the same polypeptide chain. In the structure of Dret_0059, a ketoleucine moiety is bound to the SBP, whereas a cytosine molecule is bound in the distal PAS-like domain of the tandem PAS-like domain. Differential scanning flourimetry support the binding of ligands observed in the crystal structure. There is significant interaction between the SBP and tandem PAS-like domains, and it is possible that the binding of one ligand could have an effect on the binding of the other. We uncovered three other proteins with this structural architecture in the non-redundant sequence data base, and predict that they too bind the same substrates. The genomic context of this protein did not offer any clues for its function. We did not find any biological process in which the two observed ligands are coupled. The protein Dret_0059 could be involved in either signal transduction or solute transport.« less

  14. Methods of use of cellulose binding domain proteins

    DOEpatents

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1997-09-23

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  15. Methods of use of cellulose binding domain proteins

    DOEpatents

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1997-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  16. Fluorescent-responsive synthetic C1b domains of protein kinase Cδ as reporters of specific high-affinity ligand binding.

    PubMed

    Ohashi, Nami; Nomura, Wataru; Narumi, Tetsuo; Lewin, Nancy E; Itotani, Kyoko; Blumberg, Peter M; Tamamura, Hirokazu

    2011-01-19

    Protein kinase C (PKC) is a critical cell signaling pathway involved in many disorders such as cancer and Alzheimer-type dementia. To date, evaluation of PKC ligand binding affinity has been performed by competitive studies against radiolabeled probes that are problematic for high-throughput screening. In the present study, we have developed a fluorescent-based binding assay system for identifying ligands that target the PKC ligand binding domain (C1 domain). An environmentally sensitive fluorescent dye (solvatochromic fluorophore), which has been used in multiple applications to assess protein-binding interactions, was inserted in proximity to the binding pocket of a novel PKCδ C1b domain. These resultant fluorescent-labeled δC1b domain analogues underwent a significant change in fluorescent intensity upon ligand binding, and we further demonstrate that the fluorescent δC1b domain analogues can be used to evaluate ligand binding affinity.

  17. Differential recognition of syk-binding sites by each of the two phosphotyrosine-binding pockets of the Vav SH2 domain.

    PubMed

    Chen, Chih-Hong; Piraner, Dan; Gorenstein, Nina M; Geahlen, Robert L; Beth Post, Carol

    2013-11-01

    The association of spleen tyrosine kinase (Syk), a central tyrosine kinase in B cell signaling, with Vav SH2 domain is controlled by phosphorylation of two closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies established both singly phosphorylated and doubly phosphorylated forms play a role in signaling. The structure of the doubly phosphorylated form identified a new recognition of phosphotyrosine whereby two phosphotyrosines bind simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in the specificity pocket on the opposite side of the central β-sheet. It is unknown if the specificity pocket can bind phosphotyrosine independent of phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we determined the structure of the complex between Vav1 SH2 and a peptide (SykLB-YpY) modeling the singly phosphorylated-Y346 form of Syk with unphosphorylated Y342. The nuclear magnetic resonance (NMR) data conclusively establish that recognition of phosphotyrosine is swapped between the two pockets; phosphorylated pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342 occupies what is normally the pTyr binding pocket. Nearly identical changes in chemical shifts occurred upon binding all three forms of singly and doubly phosphorylated peptides; however, somewhat smaller shift perturbations for SykLB-YpY from residues in regions of high internal mobility suggest that internal motions are coupled to binding affinity. The differential recognition that includes this swapped binding of phosphotyrosine to the specificity pocket of Vav SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains in regulating protein-protein interactions in cellular signaling. Copyright © 2013 Wiley Periodicals, Inc.

  18. Steady motion of skyrmions and domains walls under diffusive spin torques

    NASA Astrophysics Data System (ADS)

    Elías, Ricardo Gabriel; Vidal-Silva, Nicolas; Manchon, Aurélien

    2017-03-01

    We explore the role of the spin diffusion of conducting electrons in two-dimensional magnetic textures (domain walls and skyrmions) with spatial variation of the order of the spin precession length λex. The effect of diffusion reflects in four additional torques that are third order in spatial derivatives of magnetization and bilinear in λex and in the nonadiabatic parameter β'. In order to study the dynamics of the solitons when these diffusive torques are present, we derive the Thiele equation in the limit of steady motion and we compare the results with the nondiffusive limit. When considering a homogenous current these torques increase the longitudinal velocity of transverse domain walls of width Δ by a factor (λex/Δ)2(α/3), α being the magnetic damping constant. In the case of single skyrmions with core radius r0these new contributions tend to increase the Magnus effect in an amount proportional to (λex/r0) 2(1 +2 α β') .

  19. Atiyah-Patodi-Singer index theorem for domain-wall fermion Dirac operator

    NASA Astrophysics Data System (ADS)

    Fukaya, Hidenori; Onogi, Tetsuya; Yamaguchi, Satoshi

    2018-03-01

    Recently, the Atiyah-Patodi-Singer(APS) index theorem attracts attention for understanding physics on the surface of materials in topological phases. Although it is widely applied to physics, the mathematical set-up in the original APS index theorem is too abstract and general (allowing non-trivial metric and so on) and also the connection between the APS boundary condition and the physical boundary condition on the surface of topological material is unclear. For this reason, in contrast to the Atiyah-Singer index theorem, derivation of the APS index theorem in physics language is still missing. In this talk, we attempt to reformulate the APS index in a "physicist-friendly" way, similar to the Fujikawa method on closed manifolds, for our familiar domain-wall fermion Dirac operator in a flat Euclidean space. We find that the APS index is naturally embedded in the determinant of domain-wall fermions, representing the so-called anomaly descent equations.

  20. Structure of p73 DNA-binding domain tetramer modulates p73 transactivation

    PubMed Central

    Ethayathulla, Abdul S.; Tse, Pui-Wah; Monti, Paola; Nguyen, Sonha; Inga, Alberto; Fronza, Gilberto; Viadiu, Hector

    2012-01-01

    The transcription factor p73 triggers developmental pathways and overlaps stress-induced p53 transcriptional pathways. How p53-family response elements determine and regulate transcriptional specificity remains an unsolved problem. In this work, we have determined the first crystal structures of p73 DNA-binding domain tetramer bound to response elements with spacers of different length. The structure and function of the adaptable tetramer are determined by the distance between two half-sites. The structures with zero and one base-pair spacers show compact p73 DNA-binding domain tetramers with large tetramerization interfaces; a two base-pair spacer results in DNA unwinding and a smaller tetramerization interface, whereas a four base-pair spacer hinders tetramerization. Functionally, p73 is more sensitive to spacer length than p53, with one base-pair spacer reducing 90% of transactivation activity and longer spacers reducing transactivation to basal levels. Our results establish the quaternary structure of the p73 DNA-binding domain required as a scaffold to promote transactivation. PMID:22474346

  1. Structural Analysis on the Pathologic Mutant Glucocorticoid Receptor Ligand-Binding Domains.

    PubMed

    Hurt, Darrell E; Suzuki, Shigeru; Mayama, Takafumi; Charmandari, Evangelia; Kino, Tomoshige

    2016-02-01

    Glucocorticoid receptor (GR) gene mutations may cause familial or sporadic generalized glucocorticoid resistance syndrome. Most of the missense forms distribute in the ligand-binding domain and impair its ligand-binding activity and formation of the activation function (AF)-2 that binds LXXLL motif-containing coactivators. We performed molecular dynamics simulations to ligand-binding domain of pathologic GR mutants to reveal their structural defects. Several calculated parameters including interaction energy for dexamethasone or the LXXLL peptide indicate that destruction of ligand-binding pocket (LBP) is a primary character. Their LBP defects are driven primarily by loss/reduction of the electrostatic interaction formed by R611 and T739 of the receptor to dexamethasone and a subsequent conformational mismatch, which deacylcortivazol resolves with its large phenylpyrazole moiety and efficiently stimulates transcriptional activity of the mutant receptors with LBP defect. Reduced affinity of the LXXLL peptide to AF-2 is caused mainly by disruption of the electrostatic bonds to the noncore leucine residues of this peptide that determine the peptide's specificity to GR, as well as by reduced noncovalent interaction against core leucines and subsequent exposure of the AF-2 surface to solvent. The results reveal molecular defects of pathologic mutant receptors and provide important insights to the actions of wild-type GR.

  2. Structure of the effector-binding domain of the arabinose repressor AraR from Bacillus subtilis

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

    Procházková, Kateřina; Čermáková, Kateřina; Pachl, Petr

    2012-02-01

    The crystal structure of the effector-binding domain of the transcriptional repressor AraR from B. subtilis in complex with the effector molecule (l-arabinose) was determined at 2.2 Å resolution. A detailed analysis of the crystal identified a dimer organization that is distinctive from that of other members of the GalR/LacI family. In Bacillus subtilis, the arabinose repressor AraR negatively controls the expression of genes in the metabolic pathway of arabinose-containing polysaccharides. The protein is composed of two domains of different phylogenetic origin and function: an N-terminal DNA-binding domain belonging to the GntR family and a C-terminal effector-binding domain that shows similaritymore » to members of the GalR/LacI family. The crystal structure of the C-terminal effector-binding domain of AraR in complex with the effector l-arabinose has been determined at 2.2 Å resolution. The l-arabinose binding affinity was characterized by isothermal titration calorimetry and differential scanning fluorimetry; the K{sub d} value was 8.4 ± 0.4 µM. The effect of l-arabinose on the protein oligomeric state was investigated in solution and detailed analysis of the crystal identified a dimer organization which is distinctive from that of other members of the GalR/LacI family.« less

  3. MODELING THE BINDING OF THE METABOLITES OF SOME POLYCYCLIC AROMTIC HYDROCARBONS TO THE LIGAND BINDING DOMAIN OF THE ESTROGEN RECEPTOR

    EPA Science Inventory

    Modeling the binding of the metabolites of some Polycyclic Aromatic Hydrocarbons to the ligand binding domain of the estrogen receptor
    James Rabinowitz, Stephen Little, Katrina Brown, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC; Un...

  4. Magnetic properties, domain-wall creep motion, and the Dzyaloshinskii-Moriya interaction in Pt/Co/Ir thin films

    NASA Astrophysics Data System (ADS)

    Shepley, Philippa M.; Tunnicliffe, Harry; Shahbazi, Kowsar; Burnell, Gavin; Moore, Thomas A.

    2018-04-01

    We study the magnetic properties of perpendicularly magnetized Pt/Co/Ir thin films and investigate the domain-wall creep method of determining the interfacial Dzyaloshinskii-Moriya (DM) interaction in ultrathin films. Measurements of the Co layer thickness dependence of saturation magnetization, perpendicular magnetic anisotropy, and symmetric and antisymmetric (i.e., DM) exchange energies in Pt/Co/Ir thin films have been made to determine the relationship between these properties. We discuss the measurement of the DM interaction by the expansion of a reverse domain in the domain-wall creep regime. We show how the creep parameters behave as a function of in-plane bias field and discuss the effects of domain-wall roughness on the measurement of the DM interaction by domain expansion. Whereas modifications to the creep law with DM field and in-plane bias fields have taken into account changes in the energy barrier scaling parameter α , we find that both α and the velocity scaling parameter v0 change as a function of in-plane bias field.

  5. Molecular insights into the binding of phosphoinositides to the TH domain region of TIPE proteins.

    PubMed

    Antony, Priya; Baby, Bincy; Vijayan, Ranjit

    2016-11-01

    Phosphatidylinositols and their phosphorylated derivatives, phosphoinositides, play a central role in regulating diverse cellular functions. These phospholipids have been shown to interact with the hydrophobic TH domain of the tumor necrosis factor (TNF)-α-induced protein 8 (TIPE) family of proteins. However, the precise mechanism of interaction of these lipids is unclear. Here we report the binding mode and interactions of these phospholipids in the TH domain, as elucidated using molecular docking and simulations. Results indicate that phosphoinositides bind to the TH domain in a similar way by inserting their lipid tails in the hydrophobic cavity. The exposed head group is stabilized by interactions with critical positively charged residues on the surface of these proteins. Further MD simulations confirmed the dynamic stability of these lipids in the TH domain. This computational analysis thus provides insight into the binding mode of phospholipids in the TH domain of the TIPE family of proteins. Graphical abstract A phosphoinositide (phosphatidylinositol 4-phosphate; PtdIns4P) docked to TIPE2.

  6. Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain

    PubMed Central

    Sakata, Eri; Yamaguchi, Yoshiki; Kurimoto, Eiji; Kikuchi, Jun; Yokoyama, Shigeyuki; Yamada, Shingo; Kawahara, Hiroyuki; Yokosawa, Hideyoshi; Hattori, Nobutaka; Mizuno, Yoshikuni; Tanaka, Keiji; Kato, Koichi

    2003-01-01

    Parkin, a product of the causative gene of autosomal-recessive juvenile parkinsonism (AR-JP), is a RING-type E3 ubiquitin ligase and has an amino-terminal ubiquitin-like (Ubl) domain. Although a single mutation that causes an Arg to Pro substitution at position 42 of the Ubl domain (the Arg 42 mutation) has been identified in AR-JP patients, the function of this domain is not clear. In this study, we determined the three-dimensional structure of the Ubl domain of parkin by NMR, in particular by extensive use of backbone 15N-1H residual dipolar-coupling data. Inspection of chemical-shift-perturbation data showed that the parkin Ubl domain binds the Rpn10 subunit of 26S proteasomes via the region of parkin that includes position 42. Our findings suggest that the Arg 42 mutation induces a conformational change in the Rpn10-binding site of Ubl, resulting in impaired proteasomal binding of parkin, which could be the cause of AR-JP. PMID:12634850

  7. Möbius domain-wall fermions on gradient-flowed dynamical HISQ ensembles

    NASA Astrophysics Data System (ADS)

    Berkowitz, Evan; Bouchard, Chris; Chang, Chia Cheng; Clark, M. A.; Joó, Bálint; Kurth, Thorsten; Monahan, Christopher; Nicholson, Amy; Orginos, Kostas; Rinaldi, Enrico; Vranas, Pavlos; Walker-Loud, André

    2017-09-01

    We report on salient features of a mixed lattice QCD action using valence Möbius domain-wall fermions solved on the dynamical Nf=2 +1 +1 highly improved staggered quark sea-quark ensembles generated by the MILC Collaboration. The approximate chiral symmetry properties of the valence fermions are shown to be significantly improved by utilizing the gradient-flow scheme to first smear the highly improved staggered quark configurations. The greater numerical cost of the Möbius domain-wall inversions is mitigated by the highly efficient QUDA library optimized for NVIDIA GPU accelerated compute nodes. We have created an interface to this optimized QUDA solver in Chroma. We provide tuned parameters of the action and performance of QUDA using ensembles with the lattice spacings a ≃{0.15 ,0.12 ,0.09 } fm and pion masses mπ≃{310 ,220 ,130 } MeV . We have additionally generated two new ensembles with a ˜0.12 fm and mπ˜{400 ,350 } MeV . With a fixed flow time of tg f=1 in lattice units, the residual chiral symmetry breaking of the valence fermions is kept below 10% of the light quark mass on all ensembles, mres≲0.1 ×ml , with moderate values of the fifth dimension L5 and a domain-wall height M5≤1.3 . As a benchmark calculation, we perform a continuum, infinite volume, physical pion and kaon mass extrapolation of FK±/Fπ± and demonstrate our results are independent of flow time and consistent with the FLAG determination of this quantity at the level of less than one standard deviation.

  8. Longitudinal domain wall formation in elongated assemblies of ferromagnetic nanoparticles

    PubMed Central

    Varón, Miriam; Beleggia, Marco; Jordanovic, Jelena; Schiøtz, Jakob; Kasama, Takeshi; Puntes, Victor F.; Frandsen, Cathrine

    2015-01-01

    Through evaporation of dense colloids of ferromagnetic ~13 nm ε-Co particles onto carbon substrates, anisotropic magnetic dipolar interactions can support formation of elongated particle structures with aggregate thicknesses of 100–400 nm and lengths of up to some hundred microns. Lorenz microscopy and electron holography reveal collective magnetic ordering in these structures. However, in contrast to continuous ferromagnetic thin films of comparable dimensions, domain walls appear preferentially as longitudinal, i.e., oriented parallel to the long axis of the nanoparticle assemblies. We explain this unusual domain structure as the result of dipolar interactions and shape anisotropy, in the absence of inter-particle exchange coupling. PMID:26416297

  9. Prediction of small molecule binding property of protein domains with Bayesian classifiers based on Markov chains.

    PubMed

    Bulashevska, Alla; Stein, Martin; Jackson, David; Eils, Roland

    2009-12-01

    Accurate computational methods that can help to predict biological function of a protein from its sequence are of great interest to research biologists and pharmaceutical companies. One approach to assume the function of proteins is to predict the interactions between proteins and other molecules. In this work, we propose a machine learning method that uses a primary sequence of a domain to predict its propensity for interaction with small molecules. By curating the Pfam database with respect to the small molecule binding ability of its component domains, we have constructed a dataset of small molecule binding and non-binding domains. This dataset was then used as training set to learn a Bayesian classifier, which should distinguish members of each class. The domain sequences of both classes are modelled with Markov chains. In a Jack-knife test, our classification procedure achieved the predictive accuracies of 77.2% and 66.7% for binding and non-binding classes respectively. We demonstrate the applicability of our classifier by using it to identify previously unknown small molecule binding domains. Our predictions are available as supplementary material and can provide very useful information to drug discovery specialists. Given the ubiquitous and essential role small molecules play in biological processes, our method is important for identifying pharmaceutically relevant components of complete proteomes. The software is available from the author upon request.

  10. The C-terminal heavy-chain domain of botulinum neurotoxin a is not the only site that binds neurons, as the N-terminal heavy-chain domain also plays a very active role in toxin-cell binding and interactions.

    PubMed

    Ayyar, B Vijayalakshmi; Aoki, K Roger; Atassi, M Zouhair

    2015-04-01

    Botulinum neurotoxins (BoNTs) possess unique specificity for nerve terminals. They bind to the presynaptic membrane and then translocate intracellularly, where the light-chain endopeptidase cleaves the SNARE complex proteins, subverting the synaptic exocytosis responsible for acetylcholine release to the synaptic cleft. This inhibits acetylcholine binding to its receptor, causing paralysis. Binding, an obligate event for cell intoxication, is believed to occur through the heavy-chain C-terminal (HC) domain. It is followed by toxin translocation and entry into the cell cytoplasm, which is thought to be mediated by the heavy-chain N-terminal (HN) domain. Submolecular mapping analysis by using synthetic peptides spanning BoNT serotype A (BoNT/A) and mouse brain synaptosomes (SNPs) and protective antibodies against toxin from mice and cervical dystonia patients undergoing BoNT/A treatment revealed that not only regions of the HC domain but also regions of the HN domain are involved in the toxin binding process. Based on these findings, we expressed a peptide corresponding to the BoNT/A region comprising HN domain residues 729 to 845 (HN729-845). HN729-845 bound directly to mouse brain SNPs and substantially inhibited BoNT/A binding to SNPs. The binding involved gangliosides GT1b and GD1a and a few membrane lipids. The peptide bound to human or mouse neuroblastoma cells within 1 min. Peptide HN729-845 protected mice completely against a lethal BoNT/A dose (1.05 times the 100% lethal dose). This protective activity was obtained at a dose comparable to that of the peptide from positions 967 to 1296 in the HC domain. These findings strongly indicate that HN729-845 and, by extension, the HN domain are fully programmed and equipped to bind to neuronal cells and in the free state can even inhibit the binding of the toxin. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. The SARS Coronavirus 3a protein binds calcium in its cytoplasmic domain.

    PubMed

    Minakshi, Rinki; Padhan, Kartika; Rehman, Safikur; Hassan, Md Imtaiyaz; Ahmad, Faizan

    2014-10-13

    The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a positive stranded RNA virus with ∼30kb genome. Among all open reading frames (orfs) of this virus, the orf3a is the largest, and encodes a protein of 274 amino acids, named as 3a protein. Sequence analysis suggests that the orf3a aligned to one calcium pump present in Plasmodium falciparum and the enzyme glutamine synthetase found in Leptospira interrogans. This sequence similarity was found to be limited only to amino acid residues 209-264 which form the cytoplasmic domain of the orf3a. Furthermore, this region was predicted to be involved in the calcium binding. Owing to this hypothesis, we were driven to establish its calcium binding property in vitro. Here, we expressed and purified the cytoplasmic domain of the 3a protein, called Cyto3a, as a recombinant His-tagged protein in the E. coli. The calcium binding nature was established by performing various staining methods such as ruthenium red and stains-all. (45)Ca overlay method was also done to further support the data. Since the 3a protein forms ion channels, we were interested to see any conformational changes occurring in the Cyot3a upon calcium binding, using fluorescence spectroscopy and circular dichroism. These studies clearly indicate a significant change in the conformation of the Cyto3a protein after binding with calcium. Our results strongly suggest that the cytoplasmic domain of the 3a protein of SARS-CoV binds calcium in vitro, causing a change in protein conformation. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Characterization of the microtubule binding domain of microtubule actin crosslinking factor (MACF): identification of a novel group of microtubule associated proteins.

    PubMed

    Sun, D; Leung, C L; Liem, R K

    2001-01-01

    MACF (microtubule actin cross-linking factor) is a large, 608-kDa protein that can associate with both actin microfilaments and microtubules (MTs). Structurally, MACF can be divided into 3 domains: an N-terminal domain that contains both a calponin type actin-binding domain and a plakin domain; a rod domain that is composed of 23 dystrophin-like spectrin repeats; and a C-terminal domain that includes two EF-hand calcium-binding motifs, as well as a region that is homologous to two related proteins, GAR22 and Gas2. We have previously demonstrated that the C-terminal domain of MACF binds to MTs, although no homology was observed between this domain and other known microtubule-binding proteins. In this report, we describe the characterization of this microtubule-binding domain of MACF by transient transfection studies and in vitro binding assays. We found that the C-terminus of MACF contains at least two microtubule-binding regions, a GAR domain and a domain containing glycine-serine-arginine (GSR) repeats. In transfected cells, the GAR domain bound to and partially stabilized MTs to depolymerization by nocodazole. The GSR-containing domain caused MTs to form bundles that are still sensitive to nocodazole-induced depolymerization. When present together, these two domains acted in concert to bundle MTs and render them stable to nocodazole treatment. Recently, a study has shown that the N-terminal half of the plakin domain (called the M1 domain) of MACF also binds MTs. We therefore examined the microtubule binding ability of the M1 domain in the context of the entire plakin domain with and without the remaining N-terminal regions of two different MACF isoforms. Interestingly, in the presence of the surrounding sequences, the M1 domain did not bind MTs. In addition to MACF, cDNA sequences encoding the GAR and GSR-containing domains are also found in the partial human EST clone KIAA0728, which has high sequence homology to the 3' end of the MACF cDNA; hence, we refer to

  13. Molecular and functional characterization of clathrin- and AP-2-binding determinants within a disordered domain of auxilin.

    PubMed

    Scheele, Urte; Alves, Jurgen; Frank, Ronald; Duwel, Michael; Kalthoff, Christoph; Ungewickell, Ernst

    2003-07-11

    Uncoating of clathrin-coated vesicles requires the J-domain protein auxilin for targeting hsc70 to the clathrin coats and for stimulating the hsc70 ATPase activity. This results in the release of hsc70-complexed clathrin triskelia and concomitant dissociation of the coat. To understand the complex role of auxilin in uncoating and clathrin assembly in more detail, we analyzed the molecular organization of its clathrin-binding domain (amino acids 547-813). CD spectroscopy of auxilin fragments revealed that the clathrin-binding domain is almost completely disordered in solution. By systematic mapping using synthetic peptides and by site-directed mutagenesis, we identified short peptide sequences involved in clathrin heavy chain and AP-2 binding and evaluated their significance for the function of auxilin. Some of the binding determinants, including those containing sequences 674DPF and 636WDW, showed dual specificity for both clathrin and AP-2. In contrast, the two DLL motifs within the clathrin-binding domain were exclusively involved in clathrin binding. Surprisingly, they interacted not only with the N-terminal domain of the heavy chain, but also with the distal domain. Moreover, both DLL peptides proved to be essential for clathrin assembly and uncoating. In addition, we found that the motif 726NWQ is required for efficient clathrin assembly activity. Auxilin shares a number of protein-protein interaction motifs with other endocytic proteins, including AP180. We demonstrate that AP180 and auxilin compete for binding to the alpha-ear domain of AP-2. Like AP180, auxilin also directly interacts with the ear domain of beta-adaptin. On the basis of our data, we propose a refined model for the uncoating mechanism of clathrin-coated vesicles.

  14. Unusual Characteristics of the DNA Binding Domain of Epigenetic Regulatory Protein MeCP2 Determine Its Binding Specificity

    PubMed Central

    2015-01-01

    The protein MeCP2 mediates epigenetic regulation by binding methyl-CpG (mCpG) sites on chromatin. MeCP2 consists of six domains of which one, the methyl binding domain (MBD), binds mCpG sites in duplex DNA. We show that solution conditions with physiological or greater salt concentrations or the presence of nonspecific competitor DNA is necessary for the MBD to discriminate mCpG from CpG with high specificity. The specificity for mCpG over CpG is >100-fold under these solution conditions. In contrast, the MBD does not discriminate hydroxymethyl-CpG from CpG. The MBD is unusual among site-specific DNA binding proteins in that (i) specificity is not conferred by the enhanced affinity for the specific site but rather by suppression of its affinity for generic DNA, (ii) its specific binding to mCpG is highly electrostatic, and (iii) it takes up as well as displaces monovalent cations upon DNA binding. The MBD displays an unusually high affinity for single-stranded DNA independent of modification or sequence. In addition, the MBD forms a discrete dimer on DNA via a noncooperative binding pathway. Because the affinity of the second monomer is 1 order of magnitude greater than that of nonspecific binding, the MBD dimer is a unique molecular complex. The significance of these results in the context of neuronal function and development and MeCP2-related developmental disorders such as Rett syndrome is discussed. PMID:24828757

  15. Molecular Basis for Failure of “Atypical” C1 Domain of Vav1 to Bind Diacylglycerol/Phorbol Ester*

    PubMed Central

    Geczy, Tamas; Peach, Megan L.; El Kazzouli, Saïd; Sigano, Dina M.; Kang, Ji-Hye; Valle, Christopher J.; Selezneva, Julia; Woo, Wonhee; Kedei, Noemi; Lewin, Nancy E.; Garfield, Susan H.; Lim, Langston; Mannan, Poonam; Marquez, Victor E.; Blumberg, Peter M.

    2012-01-01

    C1 domains, the recognition motif of the second messenger diacylglycerol and of the phorbol esters, are classified as typical (ligand-responsive) or atypical (not ligand-responsive). The C1 domain of Vav1, a guanine nucleotide exchange factor, plays a critical role in regulation of Vav activity through stabilization of the Dbl homology domain, which is responsible for exchange activity of Vav. Although the C1 domain of Vav1 is classified as atypical, it retains a binding pocket geometry homologous to that of the typical C1 domains of PKCs. This study clarifies the basis for its failure to bind ligands. Substituting Vav1-specific residues into the C1b domain of PKCδ, we identified five crucial residues (Glu9, Glu10, Thr11, Thr24, and Tyr26) along the rim of the binding cleft that weaken binding potency in a cumulative fashion. Reciprocally, replacing these incompatible residues in the Vav1 C1 domain with the corresponding residues from PKCδ C1b (δC1b) conferred high potency for phorbol ester binding. Computer modeling predicts that these unique residues in Vav1 increase the hydrophilicity of the rim of the binding pocket, impairing membrane association and thereby preventing formation of the ternary C1-ligand-membrane binding complex. The initial design of diacylglycerol-lactones to exploit these Vav1 unique residues showed enhanced selectivity for C1 domains incorporating these residues, suggesting a strategy for the development of ligands targeting Vav1. PMID:22351766

  16. Non-canonical binding interactions of the RNA recognition motif (RRM) domains of P34 protein modulate binding within the 5S ribonucleoprotein particle (5S RNP).

    PubMed

    Kamina, Anyango D; Williams, Noreen

    2017-01-01

    RNA binding proteins are involved in many aspects of RNA metabolism. In Trypanosoma brucei, our laboratory has identified two trypanosome-specific RNA binding proteins P34 and P37 that are involved in the maturation of the 60S subunit during ribosome biogenesis. These proteins are part of the T. brucei 5S ribonucleoprotein particle (5S RNP) and P34 binds to 5S ribosomal RNA (rRNA) and ribosomal protein L5 through its N-terminus and its RNA recognition motif (RRM) domains. We generated truncated P34 proteins to determine these domains' interactions with 5S rRNA and L5. Our analyses demonstrate that RRM1 of P34 mediates the majority of binding with 5S rRNA and the N-terminus together with RRM1 contribute the most to binding with L5. We determined that the consensus ribonucleoprotein (RNP) 1 and 2 sequences, characteristic of canonical RRM domains, are not fully conserved in the RRM domains of P34. However, the aromatic amino acids previously described to mediate base stacking interactions with their RNA target are conserved in both of the RRM domains of P34. Surprisingly, mutation of these aromatic residues did not disrupt but instead enhanced 5S rRNA binding. However, we identified four arginine residues located in RRM1 of P34 that strongly impact L5 binding. These mutational analyses of P34 suggest that the binding site for 5S rRNA and L5 are near each other and specific residues within P34 regulate the formation of the 5S RNP. These studies show the unique way that the domains of P34 mediate binding with the T. brucei 5S RNP.

  17. Nonlinear dielectric response and transient current: An effective potential for ferroelectric domain wall displacement

    NASA Astrophysics Data System (ADS)

    Placeres Jiménez, Rolando; Pedro Rino, José; Marino Gonçalves, André; Antonio Eiras, José

    2013-09-01

    Ferroelectric domain walls are modeled as rigid bodies moving under the action of a potential field in a dissipative medium. Assuming that the dielectric permittivity follows the dependence ɛ '∝1/(α+βE2), it obtained the exact expression for the effective potential. Simulations of polarization current correctly predict a power law. Such results could be valuable in the study of domain wall kinetic and ultrafast polarization processes. The model is extended to poled samples allowing the study of nonlinear dielectric permittivity under subswitching electric fields. Experimental nonlinear data from PZT 20/80 thin films and Fe+3 doped PZT 40/60 ceramic are reproduced.

  18. Universal depinning transition of domain walls in ultrathin ferromagnets

    NASA Astrophysics Data System (ADS)

    Diaz Pardo, R.; Savero Torres, W.; Kolton, A. B.; Bustingorry, S.; Jeudy, V.

    2017-05-01

    We present a quantitative and comparative study of magnetic-field-driven domain-wall depinning transition in different ferromagnetic ultrathin films over a wide range of temperature. We reveal a universal scaling function accounting for both drive and thermal effects on the depinning transition, including critical exponents. The consistent description we obtain for both the depinning and subthreshold thermally activated creep motion should shed light on the universal glassy dynamics of thermally fluctuating elastic objects pinned by disordered energy landscapes.

  19. Nucleon structure from 2+1-flavor domain-wall QCD

    NASA Astrophysics Data System (ADS)

    Ohta, Shigemi

    2018-03-01

    Nucleon-structure calculations of isovector vector-and axialvector-current form factors, transversity and scalar charge, and quark momentum and helicity fractions are reported from two recent 2+1-flavor dynamical domain-wall fermions lattice-QCD ensembles generated jointly by the RIKEN-BNL-Columbia and UKQCD Collaborations with Iwasaki × dislocation-suppressing-determinatn-ratio gauge action at inverse lattice spacing of 1.378(7) GeV and pion mass values of 249.4(3) and 172.3(3) MeV.

  20. The intervening domain from MeCP2 enhances the DNA affinity of the methyl binding domain and provides an independent DNA interaction site.

    PubMed

    Claveria-Gimeno, Rafael; Lanuza, Pilar M; Morales-Chueca, Ignacio; Jorge-Torres, Olga C; Vega, Sonia; Abian, Olga; Esteller, Manel; Velazquez-Campoy, Adrian

    2017-01-31

    Methyl-CpG binding protein 2 (MeCP2) preferentially interacts with methylated DNA and it is involved in epigenetic regulation and chromatin remodelling. Mutations in MeCP2 are linked to Rett syndrome, the leading cause of intellectual retardation in girls and causing mental, motor and growth impairment. Unstructured regions in MeCP2 provide the plasticity for establishing interactions with multiple binding partners. We present a biophysical characterization of the methyl binding domain (MBD) from MeCP2 reporting the contribution of flanking domains to its structural stability and dsDNA interaction. The flanking disordered intervening domain (ID) increased the structural stability of MBD, modified its dsDNA binding profile from an entropically-driven moderate-affinity binding to an overwhelmingly enthalpically-driven high-affinity binding. Additionally, ID provided an additional site for simultaneously and autonomously binding an independent dsDNA molecule, which is a key feature linked to the chromatin remodelling and looping activity of MeCP2, as well as its ability to interact with nucleosomes replacing histone H1. The dsDNA interaction is characterized by an unusually large heat capacity linked to a cluster of water molecules trapped within the binding interface. The dynamics of disordered regions together with extrinsic factors are key determinants of MeCP2 global structural properties and functional capabilities.

  1. The intervening domain from MeCP2 enhances the DNA affinity of the methyl binding domain and provides an independent DNA interaction site

    PubMed Central

    Claveria-Gimeno, Rafael; Lanuza, Pilar M.; Morales-Chueca, Ignacio; Jorge-Torres, Olga C.; Vega, Sonia; Abian, Olga; Esteller, Manel; Velazquez-Campoy, Adrian

    2017-01-01

    Methyl-CpG binding protein 2 (MeCP2) preferentially interacts with methylated DNA and it is involved in epigenetic regulation and chromatin remodelling. Mutations in MeCP2 are linked to Rett syndrome, the leading cause of intellectual retardation in girls and causing mental, motor and growth impairment. Unstructured regions in MeCP2 provide the plasticity for establishing interactions with multiple binding partners. We present a biophysical characterization of the methyl binding domain (MBD) from MeCP2 reporting the contribution of flanking domains to its structural stability and dsDNA interaction. The flanking disordered intervening domain (ID) increased the structural stability of MBD, modified its dsDNA binding profile from an entropically-driven moderate-affinity binding to an overwhelmingly enthalpically-driven high-affinity binding. Additionally, ID provided an additional site for simultaneously and autonomously binding an independent dsDNA molecule, which is a key feature linked to the chromatin remodelling and looping activity of MeCP2, as well as its ability to interact with nucleosomes replacing histone H1. The dsDNA interaction is characterized by an unusually large heat capacity linked to a cluster of water molecules trapped within the binding interface. The dynamics of disordered regions together with extrinsic factors are key determinants of MeCP2 global structural properties and functional capabilities. PMID:28139759

  2. The PpaA/AerR regulators of photosynthesis gene expression from anoxygenic phototrophic proteobacteria contain heme-binding SCHIC domains.

    PubMed

    Moskvin, Oleg V; Gilles-Gonzalez, Marie-Alda; Gomelsky, Mark

    2010-10-01

    The SCHIC domain of the B12-binding domain family present in the Rhodobacter sphaeroides AppA protein binds heme and senses oxygen. Here we show that the predicted SCHIC domain PpaA/AerR regulators also bind heme and respond to oxygen in vitro, despite their low sequence identity with AppA.

  3. A photoaffinity scan maps regions of the p85 SH2 domain involved in phosphoprotein binding.

    PubMed

    Williams, K P; Shoelson, S E

    1993-03-15

    Src homology 2 (SH2) domains are modular phosphotyrosine binding pockets found within a wide variety of cytoplasmic signaling molecules. Here we develop a new approach to analyzing protein-protein interfaces termed photoaffinity scanning, and apply the method to map regions of the phosphatidylinositol 3-kinase p85 SH2 domain that participate in phospho-protein binding. Each residue except phosphotyrosine (pY) within a tightly binding, IRS-1-derived phosphopeptide (GNGDpYMPMSPKS) was substituted with the photoactive amino acid, benzoylphenylalanine (Bpa). Whereas most substitutions had little effect on binding affinity, Bpa substitution of either Met (+1 and +3 with respect to pY) reduced affinity 50-100-fold to confirm their importance in the pYMXM recognition motif. In three cases photolysis of SH2 domain/Bpa phosphopeptide complexes led to cross-linking of > 50% of the SH2 domain; cross-link positions were identified by microsequence, amino acid composition, and electrospray mass spectrometric analyses. Bpa-1 cross-links within alpha-helix I, whereas Bpa+1 and Bpa+4 cross-link the SH2 domain within the flexible loop C-terminal to alpha-helix II. Moreover, cross-linking at any position prevents SH2 domain cleavage at a trypsin-sensitive site within the flexible loop between beta-strands 1 and 2. Therefore, at least three distinct SH2 regions in addition to the beta-sheet participate in phosphoprotein binding; the loop cross-linked by phosphopeptide residues C-terminal to pY appears to confer specificity to the phosphoprotein/SH2 domain interaction.

  4. Functional Analysis of a Bacterial Antifreeze Protein Indicates a Cooperative Effect between Its Two Ice-Binding Domains.

    PubMed

    Wang, Chen; Oliver, Erin E; Christner, Brent C; Luo, Bing-Hao

    2016-07-19

    Antifreeze proteins make up a class of ice-binding proteins (IBPs) that are possessed and expressed by certain cold-adapted organisms to enhance their freezing tolerance. Here we report the biophysical and functional characterization of an IBP discovered in a bacterium recovered from a deep glacial ice core drilled at Vostok Station, Antarctica (IBPv). Our study showed that the recombinant protein rIBPv exhibited a thermal hysteresis of 2 °C at concentrations of >50 μM, effectively inhibited ice recrystallization, and enhanced bacterial viability during freeze-thaw cycling. Circular dichroism scans indicated that rIBPv mainly consists of β strands, and its denaturing temperature was 53.5 °C. Multiple-sequence alignment of homologous IBPs predicted that IBPv contains two ice-binding domains, a feature unique among known IBPs. To examine functional differences between the IBPv domains, each domain was cloned, expressed, and purified. The second domain (domain B) expressed greater ice binding activity. Data from thermal hysteresis and gel filtration assays supported the idea that the two domains cooperate to achieve a higher ice binding effect by forming heterodimers. However, physical linkage of the domains was not required for this effect.

  5. Current-driven second-harmonic domain wall resonance in ferromagnetic metal/nonmagnetic metal bilayers: A field-free method for spin Hall angle measurements

    NASA Astrophysics Data System (ADS)

    Hajiali, M. R.; Hamdi, M.; Roozmeh, S. E.; Mohseni, S. M.

    2017-10-01

    We study the ac current-driven domain wall motion in bilayer ferromagnetic metal (FM)/nonmagnetic metal (NM) nanowires. The solution of the modified Landau-Lifshitz-Gilbert equation including all the spin transfer torques is used to describe motion of the domain wall in the presence of the spin Hall effect. We show that the domain wall center has a second-harmonic frequency response in addition to the known first-harmonic excitation. In contrast to the experimentally observed second-harmonic response in harmonic Hall measurements of spin-orbit torque in magnetic thin films, this second-harmonic response directly originates from spin-orbit torque driven domain wall dynamics. Based on the spin current generated by domain wall dynamics, the longitudinal spin motive force generated voltage across the length of the nanowire is determined. The second-harmonic response introduces additionally a practical field-free and all-electrical method to probe the effective spin Hall angle for FM/NM bilayer structures that could be applied in experiments. Our results also demonstrate the capability of utilizing FM/NM bilayer structures in domain wall based spin-torque signal generators and resonators.

  6. Domain wall motion in sub-100 nm magnetic wire

    NASA Astrophysics Data System (ADS)

    Siddiqui, Saima; Dutta, Sumit; Currivan, Jean Anne; Ross, Caroline; Baldo, Marc

    2015-03-01

    Nonvolatile memory devices such as racetrack memory rely on the manipulation of domain wall (DW) in magnetic nanowires, and scaling of these devices requires an understanding of domain wall behavior as a function of the wire width. Due to the increased importance of edge roughness and magnetostatic interaction, DW pinning increases dramatically as the wire dimensions decrease and stochastic behavior is expected depending on the distribution of pinning sites. We report on the field driven DW statistics in sub-100 nm wide nanowires made from Co films with very small edge roughness. The nanowires were patterned in the form of a set of concentric rings of 10 μm diameter. Two different width nanowires with two different spacings have been studied. The rings were first saturated in plane to produce onion states and then the DWs were translated in the wires using an orthogonal in-plane field. The position of the DWs in the nanowires was determined with magnetic force microscopy. From the positions of the DWs in the nanowires, the strength of the extrinsic pinning sites was identified and they follow two different distributions in two different types of nanowire rings. For the closely spaced wires, magnetostatic interactions led to correlated movement of DWs in neighboring wires. The implications of DW pinning and interaction in nanoscale DW devices will be discussed.

  7. Structural and Functional Analysis of the Human HDAC4 Catalytic Domain Reveals a Regulatory Structural Zinc-binding Domain*S⃞

    PubMed Central

    Bottomley, Matthew J.; Lo Surdo, Paola; Di Giovine, Paolo; Cirillo, Agostino; Scarpelli, Rita; Ferrigno, Federica; Jones, Philip; Neddermann, Petra; De Francesco, Raffaele; Steinkühler, Christian; Gallinari, Paola; Carfí, Andrea

    2008-01-01

    Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR·HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions. PMID:18614528

  8. Exploration of interaction zones of β-tubulin colchicine binding domain of helminths and binding mechanism of anthelmintics.

    PubMed

    Ranjan, Prabodh; Kumar, Sivakumar Prasanth; Kari, Vijayakrishna; Jha, Prakash Chandra

    2017-06-01

    Numerous studies postulated the possible modes of anthelmintic activity by targeting alternate or extended regions of colchicine binding domain of helminth β-tubulin. We present three interaction zones (zones vide -1 to -3) in the colchicine binding domain of Haemonchus contortus (a helminth) β-tubulin homology model and developed zone-wise structure-based pharmacophore models coupled with molecular docking technique to unveil the binding hypotheses. The resulted ten structure-based hypotheses were then refined to essential three point pharmacophore features that captured recurring and crucial non-covalent receptor contacts and proposed three characteristics necessary for optimal zone-2 binding: a conserved pair of H bond acceptor (HBA to form H bond with Asn226 residue) and an aliphatic moiety of molecule separated by 3.75±0.44Å. Further, an aliphatic or a heterocyclic group distant (11.75±1.14Å) to the conserved aliphatic site formed the third feature component in the zone-2 specific anthelmintic pharmacophore model. Alternatively, an additional HBA can be substituted as a third component to establish H bonding with Asn204. We discern that selective zone-2 anthelmintics can be designed effectively by closely adapting the pharmacophore feature patterns and its geometrical constraints. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling

    PubMed Central

    Müller, Jennifer; Obermeier, Ingrid; Wöhner, Miriam; Brandl, Carolin; Mrotzek, Sarah; Angermüller, Sieglinde; Maity, Palash C.; Reth, Michael; Nitschke, Lars

    2013-01-01

    A high proportion of human B cells carry B-cell receptors (BCRs) that are autoreactive. Inhibitory receptors such as CD22 can downmodulate autoreactive BCR responses. With its extracellular domain, CD22 binds to sialic acids in α2,6 linkages in cis, on the surface of the same B cell or in trans, on other cells. Sialic acids are self ligands, as they are abundant in vertebrates, but are usually not expressed by pathogens. We show that cis-ligand binding of CD22 is crucial for the regulation of B-cell Ca2+ signaling by controlling the CD22 association to the BCR. Mice with a mutated CD22 ligand-binding domain of CD22 showed strongly reduced Ca2+ signaling. In contrast, mice with mutated CD22 immunoreceptor tyrosine-based inhibition motifs have increased B-cell Ca2+ responses, increased B-cell turnover, and impaired survival of the B cells. Thus, the CD22 ligand-binding domain has a crucial function in regulating BCR signaling, which is relevant for controlling autoimmunity. PMID:23836650

  10. CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling.

    PubMed

    Müller, Jennifer; Obermeier, Ingrid; Wöhner, Miriam; Brandl, Carolin; Mrotzek, Sarah; Angermüller, Sieglinde; Maity, Palash C; Reth, Michael; Nitschke, Lars

    2013-07-23

    A high proportion of human B cells carry B-cell receptors (BCRs) that are autoreactive. Inhibitory receptors such as CD22 can downmodulate autoreactive BCR responses. With its extracellular domain, CD22 binds to sialic acids in α2,6 linkages in cis, on the surface of the same B cell or in trans, on other cells. Sialic acids are self ligands, as they are abundant in vertebrates, but are usually not expressed by pathogens. We show that cis-ligand binding of CD22 is crucial for the regulation of B-cell Ca(2+) signaling by controlling the CD22 association to the BCR. Mice with a mutated CD22 ligand-binding domain of CD22 showed strongly reduced Ca(2+) signaling. In contrast, mice with mutated CD22 immunoreceptor tyrosine-based inhibition motifs have increased B-cell Ca(2+) responses, increased B-cell turnover, and impaired survival of the B cells. Thus, the CD22 ligand-binding domain has a crucial function in regulating BCR signaling, which is relevant for controlling autoimmunity.

  11. GW domains of the Listeria monocytogenes invasion protein InlB are SH3-like and mediate binding to host ligands

    PubMed Central

    Marino, Michael; Banerjee, Manidipa; Jonquières, Renaud; Cossart, Pascale; Ghosh, Partho

    2002-01-01

    InlB, a surface-localized protein of Listeria monocytogenes, induces phagocytosis in non-phagocytic mammalian cells by activating Met, a receptor tyrosine kinase. InlB also binds glycosaminoglycans and the protein gC1q-R, two additional host ligands implicated in invasion. We present the structure of InlB, revealing a highly elongated molecule with leucine-rich repeats that bind Met at one end, and GW domains that dissociably bind the bacterial surface at the other. Surprisingly, the GW domains are seen to resemble SH3 domains. Despite this, GW domains are unlikely to act as functional mimics of SH3 domains since their potential proline-binding sites are blocked or destroyed. However, we do show that the GW domains, in addition to binding glycosaminoglycans, bind gC1q-R specifically, and that this binding requires release of InlB from the bacterial surface. Dissociable attachment to the bacterial surface via the GW domains may be responsible for restricting Met activation to a small, localized area of the host cell and for coupling InlB-induced host membrane dynamics with bacterial proximity during invasion. PMID:12411480

  12. The RNA recognition motif domains of RBM5 are required for RNA binding and cancer cell proliferation inhibition

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

    Zhang, Lei; Zhang, Qing; Yang, Yu

    Highlights: • RNA recognition motif domains of RBM5 are essential for cell proliferation inhibition. • RNA recognition motif domains of RBM5 are essential for apoptosis induction. • RNA recognition motif domains of RBM5 are essential for RNA binding. • RNA recognition motif domains of RBM5 are essential for caspase-2 alternative splicing. - Abstract: RBM5 is a known putative tumor suppressor gene that has been shown to function in cell growth inhibition by modulating apoptosis. RBM5 also plays a critical role in alternative splicing as an RNA binding protein. However, it is still unclear which domains of RBM5 are required formore » RNA binding and related functional activities. We hypothesized the two putative RNA recognition motif (RRM) domains of RBM5 spanning from amino acids 98–178 and 231–315 are essential for RBM5-mediated cell growth inhibition, apoptosis regulation, and RNA binding. To investigate this hypothesis, we evaluated the activities of the wide-type and mutant RBM5 gene transfer in low-RBM5 expressing A549 cells. We found that, unlike wild-type RBM5 (RBM5-wt), a RBM5 mutant lacking the two RRM domains (RBM5-ΔRRM), is unable to bind RNA, has compromised caspase-2 alternative splicing activity, lacks cell proliferation inhibition and apoptosis induction function in A549 cells. These data provide direct evidence that the two RRM domains of RBM5 are required for RNA binding and the RNA binding activity of RBM5 contributes to its function on apoptosis induction and cell growth inhibition.« less

  13. The Interface between Catalytic and Hemopexin Domains in Matrix Metalloproteinase-1 Conceals a Collagen Binding Exosite*

    PubMed Central

    Arnold, Laurence H.; Butt, Louise E.; Prior, Stephen H.; Read, Christopher M.; Fields, Gregg B.; Pickford, Andrew R.

    2011-01-01

    Matrix metalloproteinase-1 (MMP-1) is an instigator of collagenolysis, the catabolism of triple helical collagen. Previous studies have implicated its hemopexin (HPX) domain in binding and possibly destabilizing the collagen substrate in preparation for hydrolysis of the polypeptide backbone by the catalytic (CAT) domain. Here, we use biophysical methods to study the complex formed between the MMP-1 HPX domain and a synthetic triple helical peptide (THP) that encompasses the MMP-1 cleavage site of the collagen α1(I) chain. The two components interact with 1:1 stoichiometry and micromolar affinity via a binding site within blades 1 and 2 of the four-bladed HPX domain propeller. Subsequent site-directed mutagenesis and assay implicates blade 1 residues Phe301, Val319, and Asp338 in collagen binding. Intriguingly, Phe301 is partially masked by the CAT domain in the crystal structure of full-length MMP-1 implying that transient separation of the domains is important in collagen recognition. However, mutation of this residue in the intact enzyme disrupts the CAT-HPX interface resulting in a drastic decrease in binding activity. Thus, a balanced equilibrium between these compact and dislocated states may be an essential feature of MMP-1 collagenase activity. PMID:22030392

  14. Depinning of the transverse domain wall trapped at magnetic impurities patterned in planar nanowires: Control of the wall motion using low-intensity and short-duration current pulses

    NASA Astrophysics Data System (ADS)

    Paixão, E. L. M.; Toscano, D.; Gomes, J. C. S.; Monteiro, M. G.; Sato, F.; Leonel, S. A.; Coura, P. Z.

    2018-04-01

    Understanding and controlling of domain wall motion in magnetic nanowires is extremely important for the development and production of many spintronic devices. It is well known that notches are able to pin domain walls, but their pinning potential strength are too strong and it demands high-intensity current pulses to achieve wall depinning in magnetic nanowires. However, traps of pinning can be also originated from magnetic impurities, consisting of located variations of the nanowire's magnetic properties, such as exchange stiffness constant, saturation magnetization, anisotropy constant, damping parameter, and so on. In this work, we have performed micromagnetic simulations to investigate the depinning mechanism of a transverse domain wall (TDW) trapped at an artificial magnetic defect using spin-polarized current pulses. In order to create pinning traps, a simplified magnetic impurity model, only based on a local reduction of the exchange stiffness constant, have been considered. In order to provide a background for experimental studies, we have varied the parameter related to the pinning potential strength of the magnetic impurity. By adjusting the pinning potential of magnetic impurities and choosing simultaneously a suitable current pulse, we have found that it is possible to obtain domain wall depinning by applying low-intensity and short-duration current pulses. Furthermore, it was considered a planar magnetic nanowire containing a linear distribution of equally-spaced magnetic impurities and we have demonstrated the position control of a single TDW by applying sequential current pulses; that means the wall movement from an impurity to another.

  15. Human adenovirus serotypes 3 and 5 bind to two different cellular receptors via the fiber head domain.

    PubMed Central

    Stevenson, S C; Rollence, M; White, B; Weaver, L; McClelland, A

    1995-01-01

    The adenovirus fiber protein is responsible for attachment of the virion to cell surface receptors. The identity of the cellular receptor which mediates binding is unknown, although there is evidence suggesting that two distinct adenovirus receptors interact with the group C (adenovirus type 5 [Ad5]) and the group B (Ad3) adenoviruses. In order to define the determinants of adenovirus receptor specificity, we have carried out a series of competition binding experiments using recombinant native fiber polypeptides from Ad5 and Ad3 and chimeric fiber proteins in which the head domains of Ad5 and Ad3 were exchanged. Specific binding of fiber to HeLa cell receptors was assessed with radiolabeled protein synthesized in vitro, and by competition analysis with baculovirus-expressed fiber protein. Fiber produced in vitro was found as both monomer and trimer, but only the assembled trimers had receptor binding activity. Competition data support the conclusion that Ad5 and Ad3 interact with different cellular receptors. The Ad5 receptor distribution on several cell lines was assessed with a fiber binding flow cytometric assay. HeLa cells were found to express high levels of receptor, while CHO and human diploid fibroblasts did not. A chimeric fiber containing the Ad5 fiber head domain blocked the binding of Ad5 fiber but not Ad3 fiber. Similarly, a chimeric fiber containing the Ad3 fiber head blocked the binding of labeled Ad3 fiber but not Ad5 fiber. In addition, the isolated Ad3 fiber head domain competed effectively with labeled Ad3 fiber for binding to HeLa cell receptors. These results demonstrate that the determinants of receptor binding are located in the head domain of the fiber and that the isolated head domain is capable of trimerization and binding to cellular receptors. Our results also show that it is possible to change the receptor specificity of the fiber protein by manipulation of sequences contained in the head domain. Modification or replacement of the fiber

  16. Endogenously Generated Plasmin at the Vascular Wall Injury Site Amplifies Lysine Binding Site-Dependent Plasminogen Accumulation in Microthrombi

    PubMed Central

    Brzoska, Tomasz; Tanaka-Murakami, Aki; Suzuki, Yuko; Sano, Hideto; Kanayama, Naohiro; Urano, Tetsumei

    2015-01-01

    The fibrinolytic system plays a pivotal role in the regulation of hemostasis; however, it remains unclear how and when the system is triggered to induce thrombolysis. Using intra-vital confocal fluorescence microscopy, we investigated the process of plasminogen binding to laser-induced platelet-rich microthrombi generated in the mesenteric vein of transgenic mice expressing green fluorescent protein (GFP). The accumulation of GFP-expressing platelets as well as exogenously infused Alexa Fluor 568-labeled Glu-plasminogen (Glu-plg) on the injured vessel wall was assessed by measuring the increase in the corresponding fluorescence intensities. Glu-plg accumulated in a time-dependent manner in the center of the microthrombus, where phosphatidylserine is exposed on platelet surfaces and fibrin formation takes place. The rates of binding of Glu-plg in the presence of ε-aminocaproic acid and carboxypeptidase B, as well as the rates of binding of mini-plasminogen lacking kringle domains 1-4 and lysine binding sites, were significantly lower than that of Glu-plg alone, suggesting that the binding was dependent on lysine binding sites. Furthermore, aprotinin significantly suppressed the accumulation of Glu-plg, suggesting that endogenously generated plasmin activity is a prerequisite for the accumulation. In spite of the endogenous generation of plasmin and accumulation of Glu-plg in the center of microthrombi, the microthrombi did not change in size during the 2-hour observation period. When human tissue plasminogen activator was administered intravenously, Glu-plg further accumulated and the microthrombi were lysed. Glu-plg appeared to accumulate in the center of microthrombi in the early phase of microthrombus formation, and plasmin activity and lysine binding sites were required for this accumulation. PMID:25806939

  17. Functional interaction of the DNA-binding transcription factor Sp1 through its DNA-binding domain with the histone chaperone TAF-I.

    PubMed

    Suzuki, Toru; Muto, Shinsuke; Miyamoto, Saku; Aizawa, Kenichi; Horikoshi, Masami; Nagai, Ryozo

    2003-08-01

    Transcription involves molecular interactions between general and regulatory transcription factors with further regulation by protein-protein interactions (e.g. transcriptional cofactors). Here we describe functional interaction between DNA-binding transcription factor and histone chaperone. Affinity purification of factors interacting with the DNA-binding domain of the transcription factor Sp1 showed Sp1 to interact with the histone chaperone TAF-I, both alpha and beta isoforms. This interaction was specific as Sp1 did not interact with another histone chaperone CIA nor did other tested DNA-binding regulatory factors (MyoD, NFkappaB, p53) interact with TAF-I. Interaction of Sp1 and TAF-I occurs both in vitro and in vivo. Interaction with TAF-I results in inhibition of DNA-binding, and also likely as a result of such, inhibition of promoter activation by Sp1. Collectively, we describe interaction between DNA-binding transcription factor and histone chaperone which results in negative regulation of the former. This novel regulatory interaction advances our understanding of the mechanisms of eukaryotic transcription through DNA-binding regulatory transcription factors by protein-protein interactions, and also shows the DNA-binding domain to mediate important regulatory interactions.

  18. Prediction and Experimental Evidence for Thermodynamically Stable Charged Orbital Domain Walls

    DOE PAGES

    Li, Qing’an; Gray, K. E.; Wilkins, S. B.; ...

    2014-08-18

    On theoretical grounds, we show that orbital domain walls (ODWs), which are known to exist in the charge and orbital ordered layered manganite LaSr 2Mn 2O 7, should be partially charged as a result of competition between orbital-induced strain and Coulomb repulsion. Furthermore, this unexpected result provides the necessary condition for the known thermodynamic stability of these ODWs, which are unlike the more typical domain walls that arise only from an external field. We offer experimental data consistent with this theoretical framework through a combined transport and x-ray-diffraction study. In particular, our transport data on this charge and orbital orderedmore » manganite exhibit abrupt transformations to higher conductance at a threshold electric field. As transport phenomena closely resemble effects found for sliding charge-density waves (SCDWs) in pseudo-one-dimensional (1D) materials, a SCDW along such pseudo-1D ODWs provides a natural explanation of our data. Importantly, x-ray-diffraction data eliminate heating and melting of charge order as tenable alternative explanations of our data.« less

  19. Functional Elements on SIRPα IgV domain Mediate Cell Surface Binding to CD47

    PubMed Central

    Liu, Yuan; Tong, Qiao; Zhou, Yubin; Lee, Hsiau-Wei; Yang, Jenny J.; Bühring, Hans-Jörg; Chen, Yi-Tien; Ha, Binh; Chen, Celia X-J.; Zen, Ke

    2007-01-01

    Summary SIRPα and SIRPβ1, the two major isoforms of the signal regulatory protein (SIRP) family, are co-expressed in human leukocytes but mediate distinct extracellular binding interactions and divergent cell signaling responses. Previous studies have demonstrated that binding of SIRPα with CD47, another important cell surface molecule, through the extracellular IgV domain regulates important leukocyte functions including macrophage recognition, leukocyte adhesion and transmigration. Although SIRPβ1 shares highly homologous extracellular IgV structure with SIRPα, it does not bind to CD47. In this study, we defined key amino acid residues exclusively expressing in the IgV domain of SIRPα, but not SIRPβ1, which determine the extracellular binding interaction of SIRPα to CD47. These key residues include Gln67, a small hydrophobic amino acid (Ala or Val) at the 57th position and Met102. We found that Gln67 and Ala/Val57 are critical. Mutation of either of these residues abates SIRPα directly binding to CD47. Functional cell adhesion and leukocyte transmigration assays further demonstrated central roles of Gln67 and Ala/Val57 in SIRPα extracellular binding mediated cell interactions and cell migration. Another SIRPα-specific residue, Met102, appears to assist SIRPα IgV binding through Gln67 and Ala/Val57. An essential role of these amino acids in SIRPα binding to CD47 was further confirmed by introducing these residues into the SIRPβ1 IgV domain, which dramatically converts SIRPβ1 into a CD47-binding molecule. Our results thus revealed the molecular basis by which SIRPα selectively binds to CD47 and shed new light into the structural mechanisms of SIRP isoform mediated distinctive extracellular interactions and cellular responses. PMID:17070842

  20. Functional elements on SIRPalpha IgV domain mediate cell surface binding to CD47.

    PubMed

    Liu, Yuan; Tong, Qiao; Zhou, Yubin; Lee, Hsiau-Wei; Yang, Jenny J; Bühring, Hans-Jörg; Chen, Yi-Tien; Ha, Binh; Chen, Celia X-J; Yang, Yang; Zen, Ke

    2007-01-19

    SIRPalpha and SIRPbeta1, the two major isoforms of the signal regulatory protein (SIRP) family, are co-expressed in human leukocytes but mediate distinct extracellular binding interactions and divergent cell signaling responses. Previous studies have demonstrated that binding of SIRPalpha with CD47, another important cell surface molecule, through the extracellular IgV domain regulates important leukocyte functions including macrophage recognition, leukocyte adhesion and transmigration. Although SIRPbeta1 shares highly homologous extracellular IgV structure with SIRPalpha, it does not bind to CD47. Here, we defined key amino acid residues exclusively expressing in the IgV domain of SIRPalpha, but not SIRPbeta1, which determine the extracellular binding interaction of SIRPalpha to CD47. These key residues include Gln67, a small hydrophobic amino acid (Ala or Val) at the 57th position and Met102. We found that Gln67 and Ala/Val57 are critical. Mutation of either of these residues abates SIRPalpha directly binding to CD47. Functional cell adhesion and leukocyte transmigration assays further demonstrated central roles of Gln67 and Ala/Val57 in SIRPalpha extracellular binding mediated cell interactions and cell migration. Another SIRPalpha-specific residue, Met102, appears to assist SIRPalpha IgV binding through Gln67 and Ala/Val57. An essential role of these amino acid residues in SIRPalpha binding to CD47 was further confirmed by introducing these residues into the SIRPbeta1 IgV domain, which dramatically converts SIRPbeta1 into a CD47-binding molecule. Our results thus revealed the molecular basis by which SIRPalpha binds to CD47 and shed new light into the structural mechanisms of SIRP isoform mediated distinctive extracellular interactions and cellular responses.

  1. A Key Evolutionary Mutation Enhances DNA Binding of the FOXP2 Forkhead Domain.

    PubMed

    Morris, Gavin; Fanucchi, Sylvia

    2016-04-05

    Forkhead box (FOX) transcription factors share a conserved forkhead DNA binding domain (FHD) and are key role players in the development of many eukaryotic species. Their involvement in various congenital disorders and cancers makes them clinically relevant targets for novel therapeutic strategies. Among them, the FOXP subfamily of multidomain transcriptional repressors is unique in its ability to form DNA binding homo and heterodimers. The truncated FOXP2 FHD, in the absence of the leucine zipper, exists in equilibrium between monomeric and domain-swapped dimeric states in vitro. As a consequence, determining the DNA binding properties of the FOXP2 FHD becomes inherently difficult. In this work, two FOXP2 FHD hinge loop mutants have been generated to successfully prevent both the formation (A539P) and the dissociation (F541C) of the homodimers. This allows for the separation of the two species for downstream DNA binding studies. Comparison of DNA binding of the different species using electrophoretic mobility shift assay, fluorescence anisotropy and isothermal titration calorimetry indicates that the wild-type FOXP2 FHD binds DNA as a monomer. However, comparison of the DNA-binding energetics of the monomer and wild-type FHD, reveals that there is a difference in the mechanism of binding between the two species. We conclude that the naturally occurring reverse mutation (P539A) seen in the FOXP subfamily increases DNA binding affinity and may increase the potential for nonspecific binding compared to other FOX family members.

  2. WRNIP1 accumulates at laser light irradiated sites rapidly via its ubiquitin-binding zinc finger domain and independently from its ATPase domain

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

    Nomura, Hironoshin; Yoshimura, Akari, E-mail: akari_yo@musashino-u.ac.jp; Edo, Takato

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer WRNIP1 accumulates in laser light irradiated sites very rapidly via UBZ domain. Black-Right-Pointing-Pointer The ATPase domain of WRNIP1 is dispensable for its accumulation. Black-Right-Pointing-Pointer The accumulation of WRNIP1 seems not to be dependent on the interaction with WRN. -- Abstract: WRNIP1 (Werner helicase-interacting protein 1) was originally identified as a protein that interacts with the Werner syndrome responsible gene product. WRNIP1 contains a ubiquitin-binding zinc-finger (UBZ) domain in the N-terminal region and two leucine zipper motifs in the C-terminal region. In addition, it possesses an ATPase domain in the middle of the molecule and the lysine residues servingmore » as ubiquitin acceptors in the entire of the molecule. Here, we report that WRNIP1 accumulates in laser light irradiated sites very rapidly via its ubiquitin-binding zinc finger domain, which is known to bind polyubiquitin and to be involved in ubiquitination of WRNIP1 itself. The accumulation of WRNIP1 in laser light irradiated sites also required the C-terminal region containing two leucine zippers, which is reportedly involved in the oligomerization of WRNIP1. Mutated WRNIP1 with a deleted ATPase domain or with mutations in lysine residues, which serve as ubiquitin acceptors, accumulated in laser light irradiated sites, suggesting that the ATPase domain of WRNIP1 and ubiquitination of WRNIP1 are dispensable for the accumulation.« less

  3. The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site.

    PubMed

    Bae, Jae Hyun; Lew, Erin Denise; Yuzawa, Satoru; Tomé, Francisco; Lax, Irit; Schlessinger, Joseph

    2009-08-07

    SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. However, the modest binding affinity of SH2 domains to pY containing peptides may not account for and likely represents an oversimplified mechanism for regulation of selectivity of signaling pathways in living cells. Here we describe the crystal structure of the activated tyrosine kinase domain of FGFR1 in complex with a phospholipase Cgamma fragment. The structural and biochemical data and experiments with cultured cells show that the selectivity of phospholipase Cgamma binding and signaling via activated FGFR1 are determined by interactions between a secondary binding site on an SH2 domain and a region in FGFR1 kinase domain in a phosphorylation independent manner. These experiments reveal a mechanism for how SH2 domain selectivity is regulated in vivo to mediate a specific cellular process.

  4. A Novel Plasma Membrane-Anchored Protein Regulates Xylem Cell-Wall Deposition through Microtubule-Dependent Lateral Inhibition of Rho GTPase Domains.

    PubMed

    Sugiyama, Yuki; Wakazaki, Mayumi; Toyooka, Kiminori; Fukuda, Hiroo; Oda, Yoshihisa

    2017-08-21

    Spatial control of cell-wall deposition is essential for determining plant cell shape [1]. Rho-type GTPases, together with the cortical cytoskeleton, play central roles in regulating cell-wall patterning [2]. In metaxylem vessel cells, which are the major components of xylem tissues, active ROP11 Rho GTPases form oval plasma membrane domains that locally disrupt cortical microtubules, thereby directing the formation of oval pits in secondary cell walls [3-5]. However, the regulatory mechanism that determines the planar shape of active Rho of Plants (ROP) domains is still unknown. Here we show that IQD13 associates with cortical microtubules and the plasma membrane to laterally restrict the localization of ROP GTPase domains, thereby directing the formation of oval secondary cell-wall pits. Loss and overexpression of IQD13 led to the formation of abnormally round and narrow secondary cell-wall pits, respectively. Ectopically expressed IQD13 increased the presence of parallel cortical microtubules by promoting microtubule rescue. A reconstructive approach revealed that IQD13 confines the area of active ROP domains within the lattice of the cortical microtubules, causing narrow ROP domains to form. This activity required the interaction of IQD13 with the plasma membrane. These findings suggest that IQD13 positively regulates microtubule dynamics as well as their linkage to the plasma membrane, which synergistically confines the area of active ROP domains, leading to the formation of oval secondary cell-wall pits. This finding sheds light on the role of microtubule-plasma membrane linkage as a lateral fence that determines the planar shape of Rho GTPase domains. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination.

    PubMed

    Choudhury, Nila Roy; Heikel, Gregory; Trubitsyna, Maryia; Kubik, Peter; Nowak, Jakub Stanislaw; Webb, Shaun; Granneman, Sander; Spanos, Christos; Rappsilber, Juri; Castello, Alfredo; Michlewski, Gracjan

    2017-11-08

    TRIM25 is a novel RNA-binding protein and a member of the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which plays a pivotal role in the innate immune response. However, there is scarce knowledge about its RNA-related roles in cell biology. Furthermore, its RNA-binding domain has not been characterized. Here, we reveal that the RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain, which we postulate to be a novel RNA-binding domain. Using CLIP-seq and SILAC-based co-immunoprecipitation assays, we uncover TRIM25's endogenous RNA targets and protein binding partners. We demonstrate that TRIM25 controls the levels of Zinc Finger Antiviral Protein (ZAP). Finally, we show that the RNA-binding activity of TRIM25 is important for its ubiquitin ligase activity towards itself (autoubiquitination) and its physiologically relevant target ZAP. Our results suggest that many other proteins with the PRY/SPRY domain could have yet uncharacterized RNA-binding potential. Together, our data reveal new insights into the molecular roles and characteristics of RNA-binding E3 ubiquitin ligases and demonstrate that RNA could be an essential factor in their enzymatic activity.

  6. Conduction at domain walls in insulating Pb(Zr0.2 Ti0.8)O3 thin films.

    PubMed

    Guyonnet, Jill; Gaponenko, Iaroslav; Gariglio, Stefano; Paruch, Patrycja

    2011-12-01

    Domain wall conduction in insulating Pb(Zr(0.2) Ti(0.8))O(3) thin films is demonstrated. The observed electrical conduction currents can be clearly differentiated from displacement currents associated with ferroelectric polarization switching. The domain wall conduction, nonlinear and highly asymmetric due to the specific local probe measurement geometry, shows thermal activation at high temperatures, and high stability over time. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

    PubMed Central

    Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

    2000-01-01

    Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding. PMID:10727405

  8. The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

    PubMed

    Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

    2000-04-01

    Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding.

  9. Melting of Domain Wall in Charge Ordered Dirac Electron of Organic Conductor α-(BEDT-TTF)2I3

    NASA Astrophysics Data System (ADS)

    Ohki, Daigo; Matsuno, Genki; Omori, Yukiko; Kobayashi, Akito

    2018-05-01

    The origin of charge order melting is identified by using the real space dependent mean-field theory in the extended Hubbard model describing an organic Dirac electron system α-(BEDT-TTF)2I3. In this model, the width of a domain wall which arises between different types of the charge ordered phase exhibits a divergent increase with decreasing the strength of electron-electron correlations. By analyzing the finite-size effect carefully, it is shown that the divergence coincides with a topological transition where a pair of Dirac cones merges in keeping with a finite gap. It is also clarified that the gap opening point and the topological transition point are different, which leads to the existence of an exotic massive Dirac electron phase with melted-type domain wall and gapless edge states. The present result also indicated that multiple metastable states are emerged in massive Dirac Electron phase. In the trivial charge ordered phase, the gapless domain-wall bound state takes place instead of the gapless edge states, accompanying with a form change of the domain wall from melted-type into hyperbolic-tangent-type.

  10. Salvador has an extended SARAH domain that mediates binding to Hippo kinase.

    PubMed

    Cairns, Leah; Tran, Thao; Fowl, Brendan H; Patterson, Angela; Kim, Yoo Jin; Bothner, Brian; Kavran, Jennifer M

    2018-04-13

    The Hippo pathway controls cell proliferation and differentiation through the precisely tuned activity of a core kinase cassette. The activity of Hippo kinase is modulated by interactions between its C-terminal coiled-coil, termed the SARAH domain, and the SARAH domains of either dRassF or Salvador. Here, we wanted to understand the molecular basis of SARAH domain-mediated interactions and their influence on Hippo kinase activity. We focused on Salvador, a positive effector of Hippo activity and the least well-characterized SARAH domain-containing protein. We determined the crystal structure of a complex between Salvador and Hippo SARAH domains from Drosophila This structure provided insight into the organization of the Salvador SARAH domain including a folded N-terminal extension that expands the binding interface with Hippo SARAH domain. We also found that this extension improves the solubility of the Salvador SARAH domain, enhances binding to Hippo, and is unique to Salvador. We therefore suggest expanding the definition of the Salvador SARAH domain to include this extended region. The heterodimeric assembly observed in the crystal was confirmed by cross-linked MS and provided a structural basis for the mutually exclusive interactions of Hippo with either dRassF or Salvador. Of note, Salvador influenced the kinase activity of Mst2, the mammalian Hippo homolog. In co-transfected HEK293T cells, human Salvador increased the levels of Mst2 autophosphorylation and Mst2-mediated phosphorylation of select substrates, whereas Salvador SARAH domain inhibited Mst2 autophosphorylation in vitro These results suggest Salvador enhances the effects of Hippo kinase activity at multiple points in the Hippo pathway. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Mutational analyses of Aquifex pyrophilus DNA ligase define essential domains for self-adenylation and DNA binding activity.

    PubMed

    Lim, J H; Choi, J; Kim, W; Ahn, B Y; Han, Y S

    2001-04-15

    We constructed nine deletion mutants of NAD+-dependent DNA ligase from Aquifex pyrophilus to characterize the functional domains. All of DNA ligase deletion mutants were analyzed in biochemical assays for NAD+-dependent self-adenylation, DNA binding, and nick-closing activity. Although the mutant lsub1 (91-362) included the active site lysine (KxDG), self-adenylation was not shown. However, the mutants lsub6 (1-362), lsub7 (1-516), and lsub9 (1-635) showed the same adenylation activity as that of wild type. The lsub5 (91-719), which has the C-terminal domain (487-719) as to lsub4 (91-486), showed minimal adenylation activity. These results suggest that the presence of N-terminal 90 residues is essential for the formation of an enzyme-AMP complex, while C-terminal domain (487-719) appears to play a minimal role in adenylation. It was found that the presence of C-terminal domain (487-719) is indispensable for DNA binding activity of lsub5 (91-719). The mutant lsub9 (1-635) showed reduced DNA binding activity compared to that of wild type, suggesting the contribution of the domain (636-719) for the DNA binding activity. Thus, we concluded that the N-terminal 90 residues and C-terminal domain (487-719) of NAD+-dependent DNA ligase from A. pyrophilus are mutually indispensable for binding of DNA substrate.

  12. Coarsening and persistence in a one-dimensional system of orienting arrowheads: Domain-wall kinetics with A+B→0.

    PubMed

    Khandkar, Mahendra D; Stinchcombe, Robin; Barma, Mustansir

    2017-01-01

    We demonstrate the large-scale effects of the interplay between shape and hard-core interactions in a system with left- and right-pointing arrowheads <> on a line, with reorientation dynamics. This interplay leads to the formation of two types of domain walls, >< (A) and <> (B). The correlation length in the equilibrium state diverges exponentially with increasing arrowhead density, with an ordered state of like orientations arising in the limit. In this high-density limit, the A domain walls diffuse, while the B walls are static. In time, the approach to the ordered state is described by a coarsening process governed by the kinetics of domain-wall annihilation A+B→0, quite different from the A+A→0 kinetics pertinent to the Glauber-Ising model. The survival probability of a finite set of walls is shown to decay exponentially with time, in contrast to the power-law decay known for A+A→0. In the thermodynamic limit with a finite density of walls, coarsening as a function of time t is studied by simulation. While the number of walls falls as t^{-1/2}, the fraction of persistent arrowheads decays as t^{-θ} where θ is close to 1/4, quite different from the Ising value. The global persistence too has θ=1/4, as follows from a heuristic argument. In a generalization where the B walls diffuse slowly, θ varies continuously, increasing with increasing diffusion constant.

  13. Identification of Carbohydrate-Binding Domains in the Attachment Proteins of Type 1 and Type 3 Reoviruses

    PubMed Central

    Chappell, James D.; Duong, Joy L.; Wright, Benjamin W.; Dermody, Terence S.

    2000-01-01

    The reovirus attachment protein, ς1, is responsible for strain-specific patterns of viral tropism in the murine central nervous system and receptor binding on cultured cells. The ς1 protein consists of a fibrous tail domain proximal to the virion surface and a virion-distal globular head domain. To better understand mechanisms of reovirus attachment to cells, we conducted studies to identify the region of ς1 that binds cell surface carbohydrate. Chimeric and truncated ς1 proteins derived from prototype reovirus strains type 1 Lang (T1L) and type 3 Dearing (T3D) were expressed in insect cells by using a baculovirus vector. Assessment of expressed protein susceptibility to proteolytic cleavage, binding to anti-ς1 antibodies, and oligomerization indicates that the chimeric and truncated ς1 proteins are properly folded. To assess carbohydrate binding, recombinant ς1 proteins were tested for the capacity to agglutinate mammalian erythrocytes and to bind sialic acid presented on glycophorin, the cell surface molecule bound by type 3 reovirus on human erythrocytes. Using a panel of two wild-type and ten chimeric and truncated ς1 proteins, the sialic acid-binding domain of type 3 ς1 was mapped to a region of sequence proposed to form the more amino terminal of two predicted β-sheet structures in the tail. This unit corresponds to morphologic region T(iii) observed in computer-processed electron micrographs of ς1 protein purified from virions. In contrast, the homologous region of T1L ς1 sequence was not implicated in carbohydrate binding; rather, sequences in the distal portion of the tail known as the neck were required. Results of these studies demonstrate that a functional receptor-binding domain, which uses sialic acid as its ligand, is contained within morphologic region T(iii) of the type 3 ς1 tail. Furthermore, our findings indicate that T1L and T3D ς1 proteins contain different arrangements of receptor-binding domains. PMID:10954547

  14. Identification of carbohydrate-binding domains in the attachment proteins of type 1 and type 3 reoviruses.

    PubMed

    Chappell, J D; Duong, J L; Wright, B W; Dermody, T S

    2000-09-01

    The reovirus attachment protein, sigma1, is responsible for strain-specific patterns of viral tropism in the murine central nervous system and receptor binding on cultured cells. The sigma1 protein consists of a fibrous tail domain proximal to the virion surface and a virion-distal globular head domain. To better understand mechanisms of reovirus attachment to cells, we conducted studies to identify the region of sigma1 that binds cell surface carbohydrate. Chimeric and truncated sigma1 proteins derived from prototype reovirus strains type 1 Lang (T1L) and type 3 Dearing (T3D) were expressed in insect cells by using a baculovirus vector. Assessment of expressed protein susceptibility to proteolytic cleavage, binding to anti-sigma1 antibodies, and oligomerization indicates that the chimeric and truncated sigma1 proteins are properly folded. To assess carbohydrate binding, recombinant sigma1 proteins were tested for the capacity to agglutinate mammalian erythrocytes and to bind sialic acid presented on glycophorin, the cell surface molecule bound by type 3 reovirus on human erythrocytes. Using a panel of two wild-type and ten chimeric and truncated sigma1 proteins, the sialic acid-binding domain of type 3 sigma1 was mapped to a region of sequence proposed to form the more amino terminal of two predicted beta-sheet structures in the tail. This unit corresponds to morphologic region T(iii) observed in computer-processed electron micrographs of sigma1 protein purified from virions. In contrast, the homologous region of T1L sigma1 sequence was not implicated in carbohydrate binding; rather, sequences in the distal portion of the tail known as the neck were required. Results of these studies demonstrate that a functional receptor-binding domain, which uses sialic acid as its ligand, is contained within morphologic region T(iii) of the type 3 sigma1 tail. Furthermore, our findings indicate that T1L and T3D sigma1 proteins contain different arrangements of receptor-binding

  15. Non-canonical binding interactions of the RNA recognition motif (RRM) domains of P34 protein modulate binding within the 5S ribonucleoprotein particle (5S RNP)

    PubMed Central

    Kamina, Anyango D.; Williams, Noreen

    2017-01-01

    RNA binding proteins are involved in many aspects of RNA metabolism. In Trypanosoma brucei, our laboratory has identified two trypanosome-specific RNA binding proteins P34 and P37 that are involved in the maturation of the 60S subunit during ribosome biogenesis. These proteins are part of the T. brucei 5S ribonucleoprotein particle (5S RNP) and P34 binds to 5S ribosomal RNA (rRNA) and ribosomal protein L5 through its N-terminus and its RNA recognition motif (RRM) domains. We generated truncated P34 proteins to determine these domains’ interactions with 5S rRNA and L5. Our analyses demonstrate that RRM1 of P34 mediates the majority of binding with 5S rRNA and the N-terminus together with RRM1 contribute the most to binding with L5. We determined that the consensus ribonucleoprotein (RNP) 1 and 2 sequences, characteristic of canonical RRM domains, are not fully conserved in the RRM domains of P34. However, the aromatic amino acids previously described to mediate base stacking interactions with their RNA target are conserved in both of the RRM domains of P34. Surprisingly, mutation of these aromatic residues did not disrupt but instead enhanced 5S rRNA binding. However, we identified four arginine residues located in RRM1 of P34 that strongly impact L5 binding. These mutational analyses of P34 suggest that the binding site for 5S rRNA and L5 are near each other and specific residues within P34 regulate the formation of the 5S RNP. These studies show the unique way that the domains of P34 mediate binding with the T. brucei 5S RNP. PMID:28542332

  16. Specificity and autoregulation of Notch binding by tandem WW domains in suppressor of Deltex.

    PubMed

    Jennings, Martin D; Blankley, Richard T; Baron, Martin; Golovanov, Alexander P; Avis, Johanna M

    2007-09-28

    WW domains target proline-tyrosine (PY) motifs and frequently function as tandem pairs. When studied in isolation, single WW domains are notably promiscuous and regulatory mechanisms are undoubtedly required to ensure selective interactions. Here, we show that the fourth WW domain (WW4) of Suppressor of Deltex, a modular Nedd4-like protein that down-regulates the Notch receptor, is the primary mediator of a direct interaction with a Notch-PY motif. A natural Trp to Phe substitution in WW4 reduces its affinity for general PY sequences and enhances selective interaction with the Notch-PY motif via compensatory specificity-determining interactions with PY-flanking residues. When WW4 is paired with WW3, domain-domain association, impeding proper folding, competes with Notch-PY binding to WW4. This novel mode of autoinhibition is relieved by binding of another ligand to WW3. Such cooperativity may facilitate the transient regulatory interactions observed in vivo between Su(dx) and Notch in the endocytic pathway. The highly conserved tandem arrangement of WW domains in Nedd4 proteins, and similar arrangements in more diverse proteins, suggests domain-domain communication may be integral to regulation of their associated cellular activities.

  17. Time-resolved multimodal analysis of Src Homology 2 (SH2) domain binding in signaling by receptor tyrosine kinases

    PubMed Central

    Jadwin, Joshua A; Oh, Dongmyung; Curran, Timothy G; Ogiue-Ikeda, Mari; Jia, Lin; White, Forest M; Machida, Kazuya; Yu, Ji; Mayer, Bruce J

    2016-01-01

    While the affinities and specificities of SH2 domain-phosphotyrosine interactions have been well characterized, spatio-temporal changes in phosphosite availability in response to signals, and their impact on recruitment of SH2-containing proteins in vivo, are not well understood. To address this issue, we used three complementary experimental approaches to monitor phosphorylation and SH2 binding in human A431 cells stimulated with epidermal growth factor (EGF): 1) phospho-specific mass spectrometry; 2) far-Western blotting; and 3) live cell single-molecule imaging of SH2 membrane recruitment. Far-Western and MS analyses identified both well-established and previously undocumented EGF-dependent tyrosine phosphorylation and binding events, as well as dynamic changes in binding patterns over time. In comparing SH2 binding site phosphorylation with SH2 domain membrane recruitment in living cells, we found in vivo binding to be much slower. Delayed SH2 domain recruitment correlated with clustering of SH2 domain binding sites on the membrane, consistent with membrane retention via SH2 rebinding. DOI: http://dx.doi.org/10.7554/eLife.11835.001 PMID:27071344

  18. Time-resolved multimodal analysis of Src Homology 2 (SH2) domain binding in signaling by receptor tyrosine kinases.

    PubMed

    Jadwin, Joshua A; Oh, Dongmyung; Curran, Timothy G; Ogiue-Ikeda, Mari; Jia, Lin; White, Forest M; Machida, Kazuya; Yu, Ji; Mayer, Bruce J

    2016-04-12

    While the affinities and specificities of SH2 domain-phosphotyrosine interactions have been well characterized, spatio-temporal changes in phosphosite availability in response to signals, and their impact on recruitment of SH2-containing proteins in vivo, are not well understood. To address this issue, we used three complementary experimental approaches to monitor phosphorylation and SH2 binding in human A431 cells stimulated with epidermal growth factor (EGF): 1) phospho-specific mass spectrometry; 2) far-Western blotting; and 3) live cell single-molecule imaging of SH2 membrane recruitment. Far-Western and MS analyses identified both well-established and previously undocumented EGF-dependent tyrosine phosphorylation and binding events, as well as dynamic changes in binding patterns over time. In comparing SH2 binding site phosphorylation with SH2 domain membrane recruitment in living cells, we found in vivo binding to be much slower. Delayed SH2 domain recruitment correlated with clustering of SH2 domain binding sites on the membrane, consistent with membrane retention via SH2 rebinding.

  19. Identification of the Calmodulin-Binding Domains of Fas Death Receptor

    PubMed Central

    Chang, Bliss J.; Samal, Alexandra B.; Vlach, Jiri; Fernandez, Timothy F.; Brooke, Dewey; Prevelige, Peter E.; Saad, Jamil S.

    2016-01-01

    The extrinsic apoptotic pathway is initiated by binding of a Fas ligand to the ectodomain of the surface death receptor Fas protein. Subsequently, the intracellular death domain of Fas (FasDD) and that of the Fas-associated protein (FADD) interact to form the core of the death-inducing signaling complex (DISC), a crucial step for activation of caspases that induce cell death. Previous studies have shown that calmodulin (CaM) is recruited into the DISC in cholangiocarcinoma cells and specifically interacts with FasDD to regulate the apoptotic/survival signaling pathway. Inhibition of CaM activity in DISC stimulates apoptosis significantly. We have recently shown that CaM forms a ternary complex with FasDD (2:1 CaM:FasDD). However, the molecular mechanism by which CaM binds to two distinct FasDD motifs is not fully understood. Here, we employed mass spectrometry, nuclear magnetic resonance (NMR), biophysical, and biochemical methods to identify the binding regions of FasDD and provide a molecular basis for the role of CaM in Fas–mediated apoptosis. Proteolytic digestion and mass spectrometry data revealed that peptides spanning residues 209–239 (Fas-Pep1) and 251–288 (Fas-Pep2) constitute the two CaM-binding regions of FasDD. To determine the molecular mechanism of interaction, we have characterized the binding of recombinant/synthetic Fas-Pep1 and Fas-Pep2 peptides with CaM. Our data show that both peptides engage the N- and C-terminal lobes of CaM simultaneously. Binding of Fas-Pep1 to CaM is entropically driven while that of Fas-Pep2 to CaM is enthalpically driven, indicating that a combination of electrostatic and hydrophobic forces contribute to the stabilization of the FasDD–CaM complex. Our data suggest that because Fas-Pep1 and Fas-Pep2 are involved in extensive intermolecular contacts with the death domain of FADD, binding of CaM to these regions may hinder its ability to bind to FADD, thus greatly inhibiting the initiation of apoptotic signaling

  20. The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease

    PubMed Central

    King, Oliver D.; Gitler, Aaron D.; Shorter, James

    2012-01-01

    Prions are self-templating protein conformers that are naturally transmitted between individuals and promote phenotypic change. In yeast, prion-encoded phenotypes can be beneficial, neutral or deleterious depending upon genetic background and environmental conditions. A distinctive and portable ‘prion domain’ enriched in asparagine, glutamine, tyrosine and glycine residues unifies the majority of yeast prion proteins. Deletion of this domain precludes prionogenesis and appending this domain to reporter proteins can confer prionogenicity. An algorithm designed to detect prion domains has successfully identified 19 domains that can confer prion behavior. Scouring the human genome with this algorithm enriches a select group of RNA-binding proteins harboring a canonical RNA recognition motif (RRM) and a putative prion domain. Indeed, of 210 human RRM-bearing proteins, 29 have a putative prion domain, and 12 of these are in the top 60 prion candidates in the entire genome. Startlingly, these RNA-binding prion candidates are inexorably emerging, one by one, in the pathology and genetics of devastating neurodegenerative disorders, including: amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U), Alzheimer’s disease and Huntington’s disease. For example, FUS and TDP-43, which rank 1st and 10th among RRM-bearing prion candidates, form cytoplasmic inclusions in the degenerating motor neurons of ALS patients and mutations in TDP-43 and FUS cause familial ALS. Recently, perturbed RNA-binding proteostasis of TAF15, which is the 2nd ranked RRM-bearing prion candidate, has been connected with ALS and FTLD-U. We strongly suspect that we have now merely reached the tip of the iceberg. We predict that additional RNA-binding prion candidates identified by our algorithm will soon surface as genetic modifiers or causes of diverse neurodegenerative conditions. Indeed, simple prion-like transfer mechanisms involving the

  1. Comparison between spin-orbit torques measured by domain-wall motions and harmonic measurements

    NASA Astrophysics Data System (ADS)

    Kim, Joo-Sung; Nam, Yune-Seok; Kim, Dae-Yun; Park, Yong-Keun; Park, Min-Ho; Choe, Sug-Bong

    2018-05-01

    Here we report the comparison of the spin torque efficiencies measured by three different experimental schemes for Pt/Co/X stacks with material X (= Pt, Ta, Ti, Al, Au, Pd, and Ru. 7 materials). The first two spin torque efficiencies ɛDW (1 ) and ɛDW (2 ) are quantified by the measurement of spin-torque-induced effective field for domain-wall depinning and creeping motions, respectively. The last one—longitudinal spin torque efficiency ɛL—is measured by harmonic signal measurement of the magnetization rotation with uniform magnetization configuration. The results confirm that, for all measured Pt/Co/X stacks, ɛDW (1 ) and ɛDW (2 ) are exactly consistent to each other and these two efficiencies are roughly proportional to ɛL with proportionality constant π/2, which comes from the integration over the domain-wall configuration.

  2. Domain wall roughness and creep in nanoscale crystalline ferroelectric polymers

    NASA Astrophysics Data System (ADS)

    Xiao, Z.; Poddar, Shashi; Ducharme, Stephen; Hong, X.

    2013-09-01

    We report piezo-response force microscopy studies of the static and dynamic properties of domain walls (DWs) in 11 to 36 nm thick films of crystalline ferroelectric poly(vinylidene-fluoride-trifluorethylene). The DW roughness exponent ζ ranges from 0.39 to 0.48 and the DW creep exponent μ varies from 0.20 to 0.28, revealing an unexpected effective dimensionality of ˜1.5 that is independent of film thickness. Our results suggest predominantly 2D ferroelectricity in the layered polymer and we attribute the fractal dimensionality to DW deroughening due to the correlations between the in-plane and out-of-plane polarization, an effect that can be exploited to achieve high lateral domain density for developing nanoscale ferroelectrics-based applications.

  3. Tyrosine Phosphorylation of the Lyn Src Homology 2 (SH2) Domain Modulates Its Binding Affinity and Specificity*

    PubMed Central

    Jin, Lily L.; Wybenga-Groot, Leanne E.; Tong, Jiefei; Taylor, Paul; Minden, Mark D.; Trudel, Suzanne; McGlade, C. Jane; Moran, Michael F.

    2015-01-01

    Src homology 2 (SH2) domains are modular protein structures that bind phosphotyrosine (pY)-containing polypeptides and regulate cellular functions through protein-protein interactions. Proteomics analysis showed that the SH2 domains of Src family kinases are themselves tyrosine phosphorylated in blood system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we found that phosphorylation at the conserved SH2 domain residue Y194 impacts the affinity and specificity of SH2 domain binding to pY-containing peptides and proteins. Analysis of the Lyn SH2 domain crystal structure supports a model wherein phosphorylation of Y194 on the EF loop modulates the binding pocket that engages amino acid side chains at the pY+2/+3 position. These data indicate another level of regulation wherein SH2-mediated protein-protein interactions are modulated by SH2 kinases and phosphatases. PMID:25587033

  4. Effectors of animal and plant pathogens use a common domain to bind host phosphoinositides.

    PubMed

    Salomon, Dor; Guo, Yirui; Kinch, Lisa N; Grishin, Nick V; Gardner, Kevin H; Orth, Kim

    2013-01-01

    Bacterial Type III Secretion Systems deliver effectors into host cells to manipulate cellular processes to the advantage of the pathogen. Many host targets of these effectors are found on membranes. Therefore, to identify their targets, effectors often use specialized membrane-localization domains to localize to appropriate host membranes. However, the molecular mechanisms used by many domains are unknown. Here we identify a conserved bacterial phosphoinositide-binding domain (BPD) that is found in functionally diverse Type III effectors of both plant and animal pathogens. We show that members of the BPD family functionally bind phosphoinositides and mediate localization to host membranes. Moreover, NMR studies reveal that the BPD of the newly identified Vibrio parahaemolyticus Type III effector VopR is unfolded in solution, but folds into a specific structure upon binding its ligand phosphatidylinositol-(4,5)-bisphosphate. Thus, our findings suggest a possible mechanism for promoting refolding of Type III effectors after delivery into host cells.

  5. Molecular dynamics and binding selectivity of nucleotides and polynucleotide substrates with EIF2C2/Ago2 PAZ domain.

    PubMed

    Kandeel, Mahmoud; Kitade, Yukio

    2018-02-01

    RNA interference (RNAi) constitutes a major target in drug discovery. Recently, we reported that the Argonaute protein 2 (Ago2) PAZ domain selectively binds with all ribonucleotides except adenine and poorly recognizes deoxyribonucleotides. The binding properties of the PAZ domain with polynucleotides and the molecular mechanisms of substrates' selectivity remains unclear. In this study, the binding potencies of polynucleotides and the associated conformational and dynamic changes in PAZ domain are investigated. Coinciding with nucleotides' binding profile with the PAZ domain, polyuridylate (PolyU) and polycytidylate (PolyC) were potent binders. However, K dPolyU and K dPolyC were 15.8 and 9.3μM, respectively. In contrast, polyadenylate (PolyA) binding was not detectable. Molecular dynamics (MD) simulation revealed the highest change in root mean square deviation (RMSD) with ApoPAZ or PAZ domain bound with experimentally approved, low affinity substrates, whereas stronger binding substrates such as UMP or PolyU showed minimal RMSD changes. The loop between α3 and β5 in the β-hairpin subdomain showed the most responsive change in RMSD, being highly movable in the ApoPAZ and PAZ-AMP complex. Favorable substrate recognition was associate with moderate change in secondary structure content. In conclusion, the PAZ domain retains differential substrate selectivity associated with corresponding dynamic and structural changes upon binding. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Revealing of Saccharomyces cerevisiae yeast cell wall proteins capable of binding thioflavin T, a fluorescent dye specifically interacting with amyloid fibrils.

    PubMed

    Gorkovskii, A A; Bezsonov, E E; Plotnikova, T A; Kalebina, T S; Kulaev, I S

    2009-11-01

    Proteins binding thioflavin T leading to its specific fluorescence were discovered in a fraction of noncovalently bound Saccharomyces cerevisiae yeast cell wall mannoproteins. Thioflavin-binding proteins display high resistance to trypsin digestion in solution. These data are the first experimental evidence for the presence of proteins whose properties are characteristic of amyloids in yeast cell wall, except for data on glucanotransferase Bgl2p that has amyloid properties. Our data suggest the anchoring of these proteins in the cell wall by a trypsin-sensitive part of the protein molecule. Experiments with a mutant strain devoid of the BGL2 gene suggest the compensation of absent amyloid-like protein Bgl2p by increase in contents of thioflavin-binding proteins in the cell wall.

  7. Tight binding simulation study on zigzag single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Sharma, Deepa; Jaggi, Neena; Gupta, Vishu

    2018-01-01

    Tight binding simulation studies using the density functional tight binding (DFTB) model have been performed on various zigzag single-walled carbon-nanotubes (SWCNTs) to investigate their electronic properties using DFTB module of the Material Studio Software version 7.0. Various combinations of different eigen-solvers and charge mixing schemes available in the DFTB Module have been tried to chalk out the electronic structure. The analytically deduced values of the bandgap of (9, 0) SWCNT were compared with the experimentally determined value reported in the literature. On comparison, it was found that the tight binding approximations tend to drastically underestimate the bandgap values. However, the combination of Anderson charge mixing method with standard eigensolver when implemented using the smart algorithm was found to produce fairly close results. These optimized model parameters were then used to determine the band structures of various zigzag SWCNTs. (9, 0) Single-walled Nanotube which is extensively being used for sensing NH3, CH4 and NO2 has been picked up as a reference material since its experimental bandgap value has been reported in the literature. It has been found to exhibit a finite energy bandgap in contrast to its expected metallic nature. The study is of utmost significance as it not only probes and validates the simulation route for predicting suitable properties of nanomaterials but also throws light on the comparative efficacy of the different approximation and rationalization quantum mechanical techniques used in simulation studies. Such simulation studies if used intelligently prove to be immensely useful to the material scientists as they not only save time and effort but also pave the way to new experiments by making valuable predictions.

  8. The Bcr Kinase Downregulates Ras Signaling by Phosphorylating AF-6 and Binding to Its PDZ Domain

    PubMed Central

    Radziwill, G.; Erdmann, R. A.; Margelisch, U.; Moelling, K.

    2003-01-01

    The protein kinase Bcr is a negative regulator of cell proliferation and oncogenic transformation. We identified Bcr as a ligand for the PDZ domain of the cell junction and Ras-interacting protein AF-6. The Bcr kinase phosphorylates AF-6, which subsequently allows efficient binding of Bcr to AF-6, showing that the Bcr kinase is a regulator of the PDZ domain-ligand interaction. Bcr and AF-6 colocalize in epithelial cells at the plasma membrane. In addition, Bcr, AF-6, and Ras form a trimeric complex. Bcr increases the affinity of AF-6 to Ras, and a mutant of AF-6 that lacks a specific phosphorylation site for Bcr shows a reduced binding to Ras. Wild-type Bcr, but not Bcr mutants defective in binding to AF-6, interferes with the Ras-dependent stimulation of the Raf/MEK/ERK pathway. Since AF-6 binds to Bcr via its PDZ domain and to Ras via its Ras-binding domain, we propose that AF-6 functions as a scaffold-like protein that links Bcr and Ras to cellular junctions. We suggest that this trimeric complex is involved in downregulation of Ras-mediated signaling at sites of cell-cell contact to maintain cells in a nonproliferating state. PMID:12808105

  9. Higher dimensional curved domain walls on Kähler surfaces

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

    Akbar, Fiki T., E-mail: ftakbar@fi.itb.ac.id; Gunara, Bobby E., E-mail: bobby@fi.itb.ac.id; Radjabaycolle, Flinn C.

    In this paper we study some aspects of curved BPS-like domain walls in higher dimensional gravity theory coupled to scalars where the scalars span a complex Kähler surface with scalar potential turned on. Assuming that a fake superpotential has a special form which depends on Kähler potential and a holomorphic function, we prove that BPS-like equations have a local unique solution. Then, we analyze the vacuum structure of the theory including their stability using dynamical system and their existence in ultraviolet-infrared regions using renormalization group flow.

  10. Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2.

    PubMed Central

    Nan, X; Meehan, R R; Bird, A

    1993-01-01

    MeCP2 is a chromosomal protein which binds to DNA that is methylated at CpG. In situ immunofluorescence in mouse cells has shown that the protein is most concentrated in pericentromeric heterochromatin, suggesting that MeCP2 may play a role in the formation of inert chromatin. Here we have isolated a minimal methyl-CpG binding domain (MBD) from MeCP2. MBD is 85 amino acids in length, and binds exclusively to DNA that contains one or more symmetrically methylated CpGs. MBD has negligable non-specific affinity for DNA, confirming that non-specific and methyl-CpG specific binding domains of MeCP2 are distinct. In vitro footprinting indicates that MBD binding can protect a 12 nucleotide region surrounding a methyl-CpG pair, with an approximate dissociation constant of 10(-9) M. Images PMID:8177735

  11. The rapamycin-binding domain of the protein kinase mammalian target of rapamycin is a destabilizing domain.

    PubMed

    Edwards, Sarah R; Wandless, Thomas J

    2007-05-04

    Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR) kinase. The resulting ternary complex has been used to conditionally perturb protein function, and one such method involves perturbation of a protein of interest through its mislocalization. We synthesized two rapamycin derivatives that possess large substituents at the C-16 position within the FRB-binding interface, and these derivatives were screened against a library of FRB mutants using a three-hybrid assay in Saccharomyces cerevisiae. Several FRB mutants responded to one of the rapamycin derivatives, and twenty of these mutants were further characterized in mammalian cells. The mutants most responsive to the ligand were fused to yellow fluorescent protein, and fluorescence levels in the presence and absence of the ligand were measured to determine stability of the fusion proteins. Wild-type and mutant FRB domains were expressed at low levels in the absence of the rapamycin derivative, and expression levels rose up to 10-fold upon treatment with ligand. The synthetic rapamycin derivatives were further analyzed using quantitative mass spectrometry, and one of the compounds was found to contain contaminating rapamycin. Furthermore, uncontaminated analogs retained the ability to inhibit mTOR, although with diminished potency relative to rapamycin. The ligand-dependent stability displayed by wild-type FRB and FRB mutants as well as the inhibitory potential and purity of the rapamycin derivatives should be considered as potentially confounding experimental variables when using these systems.

  12. Structural analysis of the receptor binding domain of botulinum neurotoxin serotype D

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

    Zhang, Yanfeng; Buchko, Garry W.; Qin, Lin

    2010-10-28

    Botulinum neurotoxins (BoNTs) are the most toxic proteins known. The mechanism for entry into neuronal cells for serotypes A, B, E, F, and G involves a well understood dual receptor (protein and ganglioside) process, however, the mechanism of entry for serotypes C and D remains unclear. To provide structural insights into how BoNT/D enters neuronal cells, the crystal structure of the receptor binding domain (S863-E1276) for this serotype (BoNT/D-HCR) was determined at 1.65 Å resolution. While BoNT/D-HCR adopts an overall fold similar to that observed in other known BoNT HCRs, several major structural differences are present. These structural differences aremore » located at, or near, putative receptor binding sites and may be responsible for BoNT/D host preferences. Two loops, S1195-I1204 and K1236-N1244, located on both sides of the putative protein receptor binding pocket, are displaced >10 Å relative to the corresponding residues in the crystal structures of BoNT/B and G. Obvious clashes were observed in the putative protein receptor binding site when the BoNT/B protein receptor synaptotagmin II was modeled into the BoNT/D-HCR structure. Although a ganglioside binding site has never been unambiguously identified in BoNT/D-HCR, a shallow cavity in an analogous location to the other BoNT serotypes HCR domains is observed in BoNT/D-HCR that has features compatible with membrane binding. A portion of a loop near the putative receptor binding site, K1236-N1244, is hydrophobic and solvent-exposed and may directly bind membrane lipids. Liposome-binding experiments with BoNT/D-HCR demonstrate that this membrane lipid may be phosphatidylethanolamine.« less

  13. Structural Analysis of the Receptor Binding Domain of Botulinum Neurotoxin Serotype D

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

    Y Zhang; G Buchko; L Qin

    2011-12-31

    Botulinum neurotoxins (BoNTs) are the most toxic proteins known. The mechanism for entry into neuronal cells for serotypes A, B, E, F, and G involves a well understood dual receptor (protein and ganglioside) process, however, the mechanism of entry for serotypes C and D remains unclear. To provide structural insights into how BoNT/D enters neuronal cells, the crystal structure of the receptor binding domain (S863-E1276) for this serotype (BoNT/D-HCR) was determined at 1.65{angstrom} resolution. While BoNT/D-HCR adopts an overall fold similar to that observed in other known BoNT HCRs, several major structural differences are present. These structural differences are locatedmore » at, or near, putative receptor binding sites and may be responsible for BoNT/D host preferences. Two loops, S1195-I1204 and K1236-N1244, located on both sides of the putative protein receptor binding pocket, are displaced >10{angstrom} relative to the corresponding residues in the crystal structures of BoNT/B and G. Obvious clashes were observed in the putative protein receptor binding site when the BoNT/B protein receptor synaptotagmin II was modeled into the BoNT/D-HCR structure. Although a ganglioside binding site has never been unambiguously identified in BoNT/D-HCR, a shallow cavity in an analogous location to the other BoNT serotypes HCR domains is observed in BoNT/D-HCR that has features compatible with membrane binding. A portion of a loop near the putative receptor binding site, K1236-N1244, is hydrophobic and solvent-exposed and may directly bind membrane lipids. Liposome-binding experiments with BoNT/D-HCR demonstrate that this membrane lipid may be phosphatidylethanolamine.« less

  14. Crystal Structure of the Botulinum Neurotoxin Type G Binding Domain: Insight into Cell Surface Binding

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

    Stenmark, Pål; Dong, Min; Dupuy, Jérôme

    2011-11-02

    Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-{angstrom} X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantlymore » reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent.« less

  15. Crystal structure of the botulinum neurotoxin type G binding domain: insight into cell surface binding.

    PubMed

    Stenmark, Pål; Dong, Min; Dupuy, Jérôme; Chapman, Edwin R; Stevens, Raymond C

    2010-04-16

    Botulinum neurotoxins (BoNTs) typically bind the neuronal cell surface via dual interactions with both protein receptors and gangliosides. We present here the 1.9-A X-ray structure of the BoNT serotype G (BoNT/G) receptor binding domain (residues 868-1297) and a detailed view of protein receptor and ganglioside binding regions. The ganglioside binding motif (SxWY) has a conserved structure compared to the corresponding regions in BoNT serotype A and BoNT serotype B (BoNT/B), but several features of interactions with the hydrophilic face of the ganglioside are absent at the opposite side of the motif in the BoNT/G ganglioside binding cleft. This may significantly reduce the affinity between BoNT/G and gangliosides. BoNT/G and BoNT/B share the protein receptor synaptotagmin (Syt) I/II. The Syt binding site has a conserved hydrophobic plateau located centrally in the proposed protein receptor binding interface (Tyr1189, Phe1202, Ala1204, Pro1205, and Phe1212). Interestingly, only 5 of 14 residues that are important for binding between Syt-II and BoNT/B are conserved in BoNT/G, suggesting that the means by which BoNT/G and BoNT/B bind Syt diverges more than previously appreciated. Indeed, substitution of Syt-II Phe47 and Phe55 with alanine residues had little effect on the binding of BoNT/G, but strongly reduced the binding of BoNT/B. Furthermore, an extended solvent-exposed hydrophobic loop, located between the Syt binding site and the ganglioside binding cleft, may serve as a third membrane association and binding element to contribute to high-affinity binding to the neuronal membrane. While BoNT/G and BoNT/B are homologous to each other and both utilize Syt-I/Syt-II as their protein receptor, the precise means by which these two toxin serotypes bind to Syt appears surprisingly divergent. Copyright (c) 2010. Published by Elsevier Ltd.

  16. Domain wall motion in magnetically frustrated nanorings

    NASA Astrophysics Data System (ADS)

    Lubarda, M. V.; Escobar, M. A.; Li, S.; Chang, R.; Fullerton, E. E.; Lomakin, V.

    2012-06-01

    We describe a magnetically frustrated nanoring (MFNR) configuration which is formed by introducing antiferromagnetic coupling across an interface orthogonal to the ring's circumferential direction. Such structures have the unique characteristic that only one itinerant domain wall (DW) can exist in the ring, which does not need to be nucleated or injected into the structure and can never escape making it analogous to a magnetic Möbius strip. Numerical simulations show that the DW in a MFNR can be driven consecutively around the ring with a prescribed cyclicity, and that the frequency of revolutions can be controlled by the applied field. The energy landscapes can be controlled to be flat allowing for low fields of operation or to have a barrier for thermal stability. Potential logic and memory applications of MFNRs are considered and discussed.

  17. Structural basis underlying CAC RNA recognition by the RRM domain of dimeric RNA-binding protein RBPMS

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

    Teplova, Marianna; Farazi, Thalia A.; Tuschl, Thomas

    Abstract RNA-binding protein with multiple splicing (designated RBPMS) is a higher vertebrate mRNA-binding protein containing a single RNA recognition motif (RRM). RBPMS has been shown to be involved in mRNA transport, localization and stability, with key roles in axon guidance, smooth muscle plasticity, as well as regulation of cancer cell proliferation and migration. We report on structure-function studies of the RRM domain of RBPMS bound to a CAC-containing single-stranded RNA. These results provide insights into potential topologies of complexes formed by the RBPMS RRM domain and the tandem CAC repeat binding sites as detected by photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation. Thesemore » studies establish that the RRM domain of RBPMS forms a symmetrical dimer in the free state, with each monomer binding sequence-specifically to all three nucleotides of a CAC segment in the RNA bound state. Structure-guided mutations within the dimerization and RNA-binding interfaces of RBPMS RRM on RNA complex formation resulted in both disruption of dimerization and a decrease in RNA-binding affinity as observed by size exclusion chromatography and isothermal titration calorimetry. As anticipated from biochemical binding studies, over-expression of dimerization or RNA-binding mutants of Flag-HA-tagged RBPMS were no longer able to track with stress granules in HEK293 cells, thereby documenting the deleterious effects of such mutationsin vivo.« less

  18. Refolding and characterization of the functional ligand-binding domain of human lectin-like oxidized LDL receptor.

    PubMed

    Xie, Qiuhong; Matsunaga, Shigeru; Shi, Xiaohua; Ogawa, Setsuko; Niimi, Setsuko; Wen, Zhesheng; Tokuyasu, Ken; Machida, Sachiko

    2003-11-01

    Lectin-like oxidized low-density lipoprotein receptor (LOX-1), a type II membrane protein that can recognize a variety of structurally unrelated macromolecules, plays an important role in host defense and is implicated in atherogenesis. To understand the interaction between human LOX-1 and its ligands, in this study the functional C-type lectin-like domain (CTLD) of LOX-1 was reconstituted at high efficiency from inactive aggregates in Escherichia coli using a refolding technique based on an artificial chaperone. The CD spectra of the purified domain suggested that the domain has alpha-helical structure and the blue shift of Trp residues was observed on refolding of the domain. Like wild-type hLOX-1, the refolded CTLD domain was able to bind modified LDL. Thus, even though CTLD contains six Cys residues that form disulfide bonds, it recovered its specific binding ability on refolding. This suggests that the correct disulfide bonds in CTLD were formed by the artificial chaperone technique. Although the domain lacked N-glycosylation, it showed high affinity for its ligand in surface plasmon resonance experiments. Thus, unglycosylated CTLD is sufficient for binding modified LDL.

  19. The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element.

    PubMed

    Fukunaga, Junichi; Nomura, Yusuke; Tanaka, Yoichiro; Amano, Ryo; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Sakamoto, Taiichi; Kozu, Tomoko

    2013-07-01

    AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5'-NNCCAC-3' and 5'-GCGMGN'N'-3' (M:A or C; N and N' form Watson-Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences.

  20. Influence of rotating in-plane field on vertical Bloch lines in the walls of second kind of dumbbell domains

    NASA Astrophysics Data System (ADS)

    Sun, H. Y.; Hu, H. N.; Sun, Y. P.; Nie, X. F.

    2004-08-01

    Influence of rotating in-plane field on vertical Bloch lines in the walls of second kind of dumbbell domains (IIDs) was investigated, and a critical in-plane field range [ Hip1, Hip2] of which vertical-Bloch lines (VBLs) annihilated in IIDs is found under rotating in-plane field ( Hip1 is the maximal critical in-plane-field of which hard domains remain stable, Hip2 is the minimal critical in-plane-field of which all of the hard domains convert to soft bubbles (SBs, without VBLs)). It shows that the in-plane field range [ Hip1, Hip2] changes with the change of the rotating angle Δ ϕ. Hip1 maintains stable, while Hip2 decreases with the decreasing of rotating angle Δ ϕ. Comparing it with the spontaneous shrinking experiment of IIDs under both bias field and in-plane field, we presume that under the application of in-plane field there exists a direction along which the VBLs in the domain walls annihilate most easily, and it is in the direction that domain walls are perpendicular to the in-plane field.

  1. Munc13 homology domain-1 in CAPS/UNC31 mediates SNARE binding required for priming vesicle exocytosis.

    PubMed

    Khodthong, Chuenchanok; Kabachinski, Greg; James, Declan J; Martin, Thomas F J

    2011-08-03

    Neuropeptide and peptide hormone secretion from neural and endocrine cells occurs by Ca(2+)-triggered dense-core vesicle exocytosis. The membrane fusion machinery consisting of vesicle and plasma membrane SNARE proteins needs to be assembled for Ca(2+)-triggered vesicle exocytosis. The related Munc13 and CAPS/UNC31 proteins that prime vesicle exocytosis are proposed to promote SNARE complex assembly. CAPS binds SNARE proteins and stimulates SNARE complex formation on liposomes, but the relevance of SNARE binding to CAPS function in cells had not been determined. Here we identify a core SNARE-binding domain in CAPS as corresponding to Munc13 homology domain-1 (MHD1). CAPS lacking a single helix in MHD1 was unable to bind SNARE proteins or to support the Ca(2+)-triggered exocytosis of either docked or newly arrived dense-core vesicles. The results show that MHD1 is a SNARE-binding domain and that SNARE protein binding is essential for CAPS function in dense-core vesicle exocytosis. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Comparison and correlation of binding mode of ATP in the kinase domains of Hexokinase family

    PubMed Central

    Kumar, Yellapu Nanda; Kumar, Pasupuleti Santhosh; Sowjenya, Gopal; Rao, Valasani Koteswara; Yeswanth, Sthanikam; Prasad, Uppu Venkateswara; Pradeepkiran, Jangampalli Adi; Sarma, PVGK; Bhaskar, Matcha

    2012-01-01

    Hexokinases (HKs) are the enzymes that catalyses the ATP dependent phosphorylation of Hexose sugars to Hexose-6-Phosphate (Hex-6-P). There exist four different forms of HKs namely HK-I, HK-II, HK-III and HK-IV and all of them share a common ATP binding site core surrounded by more variable sequence that determine substrate affinities. Although they share a common binding site but they differ in their kinetic functions, hence the present study is aimed to analyze the binding mode of ATP. The analysis revealed that the four ATP binding domains are showing 13 identical, 7 similar and 6 dissimilar residues with similar structural conformation. Molecular docking of ATP into the kinase domains using Molecular Operating Environment (MOE) soft ware tool clearly showed the variation in the binding mode of ATP with variable docking scores. This probably explains the variable phosphorylation rates among hexokinases family. PMID:22829728

  3. Comprehensive comparative analysis and identification of RNA-binding protein domains: multi-class classification and feature selection.

    PubMed

    Jahandideh, Samad; Srinivasasainagendra, Vinodh; Zhi, Degui

    2012-11-07

    RNA-protein interaction plays an important role in various cellular processes, such as protein synthesis, gene regulation, post-transcriptional gene regulation, alternative splicing, and infections by RNA viruses. In this study, using Gene Ontology Annotated (GOA) and Structural Classification of Proteins (SCOP) databases an automatic procedure was designed to capture structurally solved RNA-binding protein domains in different subclasses. Subsequently, we applied tuned multi-class SVM (TMCSVM), Random Forest (RF), and multi-class ℓ1/ℓq-regularized logistic regression (MCRLR) for analysis and classifying RNA-binding protein domains based on a comprehensive set of sequence and structural features. In this study, we compared prediction accuracy of three different state-of-the-art predictor methods. From our results, TMCSVM outperforms the other methods and suggests the potential of TMCSVM as a useful tool for facilitating the multi-class prediction of RNA-binding protein domains. On the other hand, MCRLR by elucidating importance of features for their contribution in predictive accuracy of RNA-binding protein domains subclasses, helps us to provide some biological insights into the roles of sequences and structures in protein-RNA interactions.

  4. Coarsening and persistence in a one-dimensional system of orienting arrowheads: Domain-wall kinetics with A +B →0

    NASA Astrophysics Data System (ADS)

    Khandkar, Mahendra D.; Stinchcombe, Robin; Barma, Mustansir

    2017-01-01

    We demonstrate the large-scale effects of the interplay between shape and hard-core interactions in a system with left- and right-pointing arrowheads <> on a line, with reorientation dynamics. This interplay leads to the formation of two types of domain walls, >< (A ) and <> (B ). The correlation length in the equilibrium state diverges exponentially with increasing arrowhead density, with an ordered state of like orientations arising in the limit. In this high-density limit, the A domain walls diffuse, while the B walls are static. In time, the approach to the ordered state is described by a coarsening process governed by the kinetics of domain-wall annihilation A +B →0 , quite different from the A +A →0 kinetics pertinent to the Glauber-Ising model. The survival probability of a finite set of walls is shown to decay exponentially with time, in contrast to the power-law decay known for A +A →0 . In the thermodynamic limit with a finite density of walls, coarsening as a function of time t is studied by simulation. While the number of walls falls as t-1/2, the fraction of persistent arrowheads decays as t-θ where θ is close to 1/4 , quite different from the Ising value. The global persistence too has θ =1/4 , as follows from a heuristic argument. In a generalization where the B walls diffuse slowly, θ varies continuously, increasing with increasing diffusion constant.

  5. Tyrosine phosphorylation of the Lyn Src homology 2 (SH2) domain modulates its binding affinity and specificity.

    PubMed

    Jin, Lily L; Wybenga-Groot, Leanne E; Tong, Jiefei; Taylor, Paul; Minden, Mark D; Trudel, Suzanne; McGlade, C Jane; Moran, Michael F

    2015-03-01

    Src homology 2 (SH2) domains are modular protein structures that bind phosphotyrosine (pY)-containing polypeptides and regulate cellular functions through protein-protein interactions. Proteomics analysis showed that the SH2 domains of Src family kinases are themselves tyrosine phosphorylated in blood system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we found that phosphorylation at the conserved SH2 domain residue Y(194) impacts the affinity and specificity of SH2 domain binding to pY-containing peptides and proteins. Analysis of the Lyn SH2 domain crystal structure supports a model wherein phosphorylation of Y(194) on the EF loop modulates the binding pocket that engages amino acid side chains at the pY+2/+3 position. These data indicate another level of regulation wherein SH2-mediated protein-protein interactions are modulated by SH2 kinases and phosphatases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. A high-resolution structure of the DNA-binding domain of AhrC, the arginine repressor/activator protein from Bacillus subtilis

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

    Garnett, James A.; Baumberg, Simon; Stockley, Peter G.

    2007-11-01

    The structure of the winged helix–turn–helix DNA-binding domain of AhrC has been determined at 1.0 Å resolution. The largely hydrophobic β-wing shows high B factors and may mediate the dimer interface in operator complexes. In Bacillus subtilis the concentration of l-arginine is controlled by the transcriptional regulator AhrC, which interacts with 18 bp DNA operator sites called ARG boxes in the promoters of arginine biosynthetic and catabolic operons. AhrC is a 100 kDa homohexamer, with each subunit having two domains. The C-terminal domains form the core, mediating intersubunit interactions and binding of the co-repressor l-arginine, whilst the N-terminal domains containmore » a winged helix–turn–helix DNA-binding motif and are arranged around the periphery. The N-terminal domain of AhrC has been expressed, purified and characterized and it has been shown that the fragment still binds DNA operators as a recombinant monomer. The DNA-binding domain has also been crystallized and the crystal structure refined to 1.0 Å resolution is presented.« less

  7. Common functionally important motions of the nucleotide-binding domain of Hsp70.

    PubMed

    Gołaś, Ewa I; Czaplewski, Cezary; Scheraga, Harold A; Liwo, Adam

    2015-02-01

    The 70 kDa heat shock proteins (Hsp70) are a family of molecular chaperones involved in protein folding, aggregate prevention, and protein disaggregation. They consist of the substrate-binding domain (SBD) that binds client substrates, and the nucleotide-binding domain (NBD), whose cycles of nucleotide hydrolysis and exchange underpin the activity of the chaperone. To characterize the structure-function relationships that link the binding state of the NBD to its conformational behavior, we analyzed the dynamics of the NBD of the Hsp70 chaperone from Bos taurus (PDB 3C7N:B) by all-atom canonical molecular dynamics simulations. It was found that essential motions within the NBD fall into three major classes: the mutual class, reflecting tendencies common to all binding states, and the ADP- and ATP-unique classes, which reflect conformational trends that are unique to either the ADP- or ATP-bound states, respectively. "Mutual" class motions generally describe "in-plane" and/or "out-of-plane" (scissor-like) rotation of the subdomains within the NBD. This result is consistent with experimental nuclear magnetic resonance data on the NBD. The "unique" class motions target specific regions on the NBD, usually surface loops or sites involved in nucleotide binding and are, therefore, expected to be involved in allostery and signal transmission. For all classes, and especially for those of the "unique" type, regions of enhanced mobility can be identified; these are termed "hot spots," and their locations generally parallel those found by NMR spectroscopy. The presence of magnesium and potassium cations in the nucleotide-binding pocket was also found to influence the dynamics of the NBD significantly. © 2014 Wiley Periodicals, Inc.

  8. SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family.

    PubMed

    Antonets, Denis V; Nepomnyashchikh, Tatyana S; Shchelkunov, Sergei N

    2010-10-27

    Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.

  9. On the binding determinants of the glutamate agonist with the glutamate receptor ligand binding domain.

    PubMed

    Speranskiy, Kirill; Kurnikova, Maria

    2005-08-30

    Ionotropic glutamate receptors (GluRs) are ligand-gated membrane channel proteins found in the central neural system that mediate a fast excitatory response of neurons. In this paper, we report theoretical analysis of the ligand-protein interactions in the binding pocket of the S1S2 (ligand binding) domain of the GluR2 receptor in the closed conformation. By utilizing several theoretical methods ranging from continuum electrostatics to all-atom molecular dynamics simulations and quantum chemical calculations, we were able to characterize in detail glutamate agonist binding to the wild-type and E705D mutant proteins. A theoretical model of the protein-ligand interactions is validated via direct comparison of theoretical and Fourier transform infrared spectroscopy (FTIR) measured frequency shifts of the ligand's carboxylate group vibrations [Jayaraman et al. (2000) Biochemistry 39, 8693-8697; Cheng et al. (2002) Biochemistry 41, 1602-1608]. A detailed picture of the interactions in the binding site is inferred by analyzing contributions to vibrational frequencies produced by protein residues forming the ligand-binding pocket. The role of mobility and hydrogen-bonding network of water in the ligand-binding pocket and the contribution of protein residues exposed in the binding pocket to the binding and selectivity of the ligand are discussed. It is demonstrated that the molecular surface of the protein in the ligand-free state has mainly positive electrostatic potential attractive to the negatively charged ligand, and the potential produced by the protein in the ligand-binding pocket in the closed state is complementary to the distribution of the electrostatic potential produced by the ligand itself. Such charge complementarity ensures specificity to the unique charge distribution of the ligand.

  10. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

    PubMed Central

    Alejo, Alí; Ruiz-Argüello, M. Begoña; Ho, Yin; Smith, Vincent P.; Saraiva, Margarida; Alcami, Antonio

    2006-01-01

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis. PMID:16581912

  11. A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus.

    PubMed

    Alejo, Alí; Ruiz-Argüello, M Begoña; Ho, Yin; Smith, Vincent P; Saraiva, Margarida; Alcami, Antonio

    2006-04-11

    Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

  12. Evidence for a role for the phosphotyrosine-binding domain of Shc in interleukin 2 signaling.

    PubMed Central

    Ravichandran, K S; Igras, V; Shoelson, S E; Fesik, S W; Burakoff, S J

    1996-01-01

    Stimulation via the T-cell growth factor interleukin 2 (IL-2) leads to tyrosine phosphorylation of Shc, the interaction of Shc with Grb2, and the Ras GTP/GDP exchange factor, mSOS. Shc also coprecipitates with the IL-2 receptor (IL-2R), and therefore, may link IL-2R to Ras activation. We have further characterized the Shc-IL-2R interaction and have made the following observations. (i) Among the two phosphotyrosine-interaction domains present in Shc, the phosphotyrosine-binding (PTB) domain, rather than its SH2 domain, interacts with the tyrosine-phosphorylated IL-2R beta chain. Moreover, the Shc-PTB domain binds a phosphopeptide derived from the IL-2R beta chain (corresponding to residues surrounding Y338, SCFTNQGpYFF) with high affinity. (ii) In vivo, mutant IL-2R beta chains lacking the acidic region of IL-2Rbeta (which contains Y338) fail to phosphorylate Shc. Furthermore, when wild type or mutant Shc proteins that lack the PTB domain were expressed in the IL-2-dependent CTLL-20 cell line, an intact Shc-PTB domain was required for Shc phosphorylation by the IL-2R, which provides further support for a Shc-PTB-IL-2R interaction in vivo. (iii) PTB and SH2 domains of Shc associate with different proteins in IL-2- and T-cell-receptor-stimulated lysates, suggesting that Shc, through the concurrent use of its two different phosphotyrosine-binding domains, could assemble multiple protein complexes. Taken together, our in vivo and in vitro observations suggest that the PTB domain of Shc interacts with Y338 of the IL-2R and provide evidence for a functional role for the Shc-PTB domain in IL-2 signaling. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8643566

  13. Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization.

    PubMed

    Gong, Xin; Qian, Hongwu; Shao, Wei; Li, Jingxian; Wu, Jianping; Liu, Jun-Jie; Li, Wenqi; Wang, Hong-Wei; Espenshade, Peter; Yan, Nieng

    2016-11-01

    Sterol regulatory element-binding protein (SREBP) transcription factors are master regulators of cellular lipid homeostasis in mammals and oxygen-responsive regulators of hypoxic adaptation in fungi. SREBP C-terminus binds to the WD40 domain of SREBP cleavage-activating protein (SCAP), which confers sterol regulation by controlling the ER-to-Golgi transport of the SREBP-SCAP complex and access to the activating proteases in the Golgi. Here, we biochemically and structurally show that the carboxyl terminal domains (CTD) of Sre1 and Scp1, the fission yeast SREBP and SCAP, form a functional 4:4 oligomer and Sre1-CTD forms a dimer of dimers. The crystal structure of Sre1-CTD at 3.5 Å and cryo-EM structure of the complex at 5.4 Å together with in vitro biochemical evidence elucidate three distinct regions in Sre1-CTD required for Scp1 binding, Sre1-CTD dimerization and tetrameric formation. Finally, these structurally identified domains are validated in a cellular context, demonstrating that the proper 4:4 oligomeric complex formation is required for Sre1 activation.

  14. The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element

    PubMed Central

    Fukunaga, Junichi; Nomura, Yusuke; Tanaka, Yoichiro; Amano, Ryo; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Sakamoto, Taiichi; Kozu, Tomoko

    2013-01-01

    AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5′-NNCCAC-3′ and 5′-GCGMGN′N′-3′ (M:A or C; N and N′ form Watson–Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences. PMID:23709277

  15. In Silico Screening for Inhibitors of P-Glycoprotein That Target the Nucleotide Binding Domains

    PubMed Central

    Brewer, Frances K.; Follit, Courtney A.; Vogel, Pia D.

    2014-01-01

    Multidrug resistances and the failure of chemotherapies are often caused by the expression or overexpression of ATP-binding cassette transporter proteins such as the multidrug resistance protein, P-glycoprotein (P-gp). P-gp is expressed in the plasma membrane of many cell types and protects cells from accumulation of toxins. P-gp uses ATP hydrolysis to catalyze the transport of a broad range of mostly hydrophobic compounds across the plasma membrane and out of the cell. During cancer chemotherapy, the administration of therapeutics often selects for cells which overexpress P-gp, thereby creating populations of cancer cells resistant to a variety of chemically unrelated chemotherapeutics. The present study describes extremely high-throughput, massively parallel in silico ligand docking studies aimed at identifying reversible inhibitors of ATP hydrolysis that target the nucleotide-binding domains of P-gp. We used a structural model of human P-gp that we obtained from molecular dynamics experiments as the protein target for ligand docking. We employed a novel approach of subtractive docking experiments that identified ligands that bound predominantly to the nucleotide-binding domains but not the drug-binding domains of P-gp. Four compounds were found that inhibit ATP hydrolysis by P-gp. Using electron spin resonance spectroscopy, we showed that at least three of these compounds affected nucleotide binding to the transporter. These studies represent a successful proof of principle demonstrating the potential of targeted approaches for identifying specific inhibitors of P-gp. PMID:25270578

  16. Functional relationship between CABIT, SAM and 14-3-3 binding domains of GAREM1 that play a role in its subcellular localization

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

    Nishino, Tasuku; Matsunaga, Ryota; Konishi, Hiroaki, E-mail: hkonishi@pu-hiroshima.ac.jp

    2015-08-21

    GAREM1 (Grb2-associated regulator of Erk/MAPK1) is an adaptor protein that is involved in the epidermal growth factor (EGF) pathway. The nuclear localization of GAREM1 depends on the nuclear localization sequence (NLS), which is located at the N-terminal CABIT (cysteine-containing, all in Themis) domain. Here, we identified 14-3-3ε as a GAREM-binding protein, and its binding site is closely located to the NLS. This 14-3-3 binding site was of the atypical type and independent of GAREM phosphorylation. Moreover, the binding of 14-3-3 had an effect on the nuclear localization of GAREM1. Unexpectedly, we observed that the CABIT domain had intramolecular association withmore » the C-terminal SAM (sterile alpha motif) domain. This association might be inhibited by binding of 14-3-3 at the CABIT domain. Our results demonstrate that the mechanism underlying the nuclear localization of GAREM1 depends on its NLS in the CABIT domain, which is controlled by the binding of 14-3-3 and the C-terminal SAM domain. We suggest that the interplay between 14-3-3, SAM domain and CABIT domain might be responsible for the distribution of GAREM1 in mammalian cells. - Highlights: • 14-3-3ε regulated the nuclear localization of GAREM1 as its binding partner. • The atypical 14-3-3 binding site of GAREM1 is located near the NLS in CABIT domain. • The CABIT domain had intramolecular association with the SAM domain in GAREM1. • Subcellular localization of GAREM1 is affected with its CABIT-SAM interaction.« less

  17. Characterisation of single domain ATP-binding cassette protien homologues of Theileria parva.

    PubMed

    Kibe, M K; Macklin, M; Gobright, E; Bishop, R; Urakawa, T; ole-MoiYoi, O K

    2001-09-01

    Two distinct genes encoding single domain, ATP-binding cassette transport protein homologues of Theileria parva were cloned and sequenced. Neither of the genes is tandemly duplicated. One gene, TpABC1, encodes a predicted protein of 593 amino acids with an N-terminal hydrophobic domain containing six potential membrane-spanning segments. A single discontinuous ATP-binding element was located in the C-terminal region of TpABC1. The second gene, TpABC2, also contains a single C-terminal ATP-binding motif. Copies of TpABC2 were present at four loci in the T. parva genome on three different chromosomes. TpABC1 exhibited allelic polymorphism between stocks of the parasite. Comparison of cDNA and genomic sequences revealed that TpABC1 contained seven short introns, between 29 and 84 bp in length. The full-length TpABC1 protein was expressed in insect cells using the baculovirus system. Application of antibodies raised against the recombinant antigen to western blots of T. parva piroplasm lysates detected an 85 kDa protein in this life-cycle stage.

  18. A novel signal transduction protein: Combination of solute binding and tandem PAS-like sensor domains in one polypeptide chain.

    PubMed

    Wu, R; Wilton, R; Cuff, M E; Endres, M; Babnigg, G; Edirisinghe, J N; Henry, C S; Joachimiak, A; Schiffer, M; Pokkuluri, P R

    2017-04-01

    We report the structural and biochemical characterization of a novel periplasmic ligand-binding protein, Dret_0059, from Desulfohalobium retbaense DSM 5692, an organism isolated from Lake Retba, in Senegal. The structure of the protein consists of a unique combination of a periplasmic solute binding protein (SBP) domain at the N-terminal and a tandem PAS-like sensor domain at the C-terminal region. SBP domains are found ubiquitously, and their best known function is in solute transport across membranes. PAS-like sensor domains are commonly found in signal transduction proteins. These domains are widely observed as parts of many protein architectures and complexes but have not been observed previously within the same polypeptide chain. In the structure of Dret_0059, a ketoleucine moiety is bound to the SBP, whereas a cytosine molecule is bound in the distal PAS-like domain of the tandem PAS-like domain. Differential scanning flourimetry support the binding of ligands observed in the crystal structure. There is significant interaction between the SBP and tandem PAS-like domains, and it is possible that the binding of one ligand could have an effect on the binding of the other. We uncovered three other proteins with this structural architecture in the non-redundant sequence data base, and predict that they too bind the same substrates. The genomic context of this protein did not offer any clues for its function. We did not find any biological process in which the two observed ligands are coupled. The protein Dret_0059 could be involved in either signal transduction or solute transport. © 2017 The Protein Society.

  19. Specific phosphopeptide binding regulates a conformational change in the PI 3-kinase SH2 domain associated with enzyme activation.

    PubMed Central

    Shoelson, S E; Sivaraja, M; Williams, K P; Hu, P; Schlessinger, J; Weiss, M A

    1993-01-01

    SH2 (src-homology 2) domains define a newly recognized binding motif that mediates the physical association of target phosphotyrosyl proteins with downstream effector enzymes. An example of such phosphoprotein-effector coupling is provided by the association of phosphatidylinositol 3-kinase (PI 3-kinase) with specific phosphorylation sites within the PDGF receptor, the c-Src/polyoma virus middle T antigen complex and the insulin receptor substrate IRS-1. Notably, phosphoprotein association with the SH2 domains of p85 also stimulates an increase in catalytic activity of the PI 3-kinase p110 subunit, which can be mimicked by phosphopeptides corresponding to targeted phosphoprotein phosphorylation sites. To investigate how phosphoprotein binding to the p85 SH2 domain stimulates p110 catalytic activation, we have examined the differential effects of phosphotyrosine and PDGF receptor-, IRS-1- and c-Src-derived phosphopeptides on the conformation of an isolated SH2 domain of PI 3-kinase. Although phosphotyrosine and both activating and non-activating phosphopeptides bind to the SH2 domain, activating phosphopeptides bind with higher affinity and induce a qualitatively distinct conformational change as monitored by CD and NMR spectroscopy. Amide proton exchange and protease protection assays further show that high affinity, specific phosphopeptide binding induces non-local dynamic SH2 domain stabilization. Based on these findings we propose that specific phosphoprotein binding to the p85 subunit induces a change in SH2 domain structure which is transmitted to the p110 subunit and regulates enzymatic activity by an allosteric mechanism. Images PMID:8382612

  20. [Preparation of anti-hCG single domain antibody by antibody grafting technique using an antigen-binding peptide].

    PubMed

    Peng, Jing; Wang, Qiong; Cheng, Xiaoling; Liu, Mengwen; Wang, Mei; Xin, Huawei

    2018-04-25

    We used the antibody grafting technology to prepare anti-hCG single-domain antibodies on the basis of antigen-binding peptide to simplify the single-domain antibody preparation process and improving the biochemical stability of peptide. By using a universal single-domain antibody backbone (cAbBCII10), CDR1 or CDR3 was replaced by the hCG-binding peptide, and the grafted antibody gene sequences were synthesized and cloned into the prokaryotic expression vector pET30a(+) in fusion with a C-terminal sfGFP gene, i.e. pET30a-(His6)-cAbBCII10-CDR1/hCGBP1-sfGFP and pET30a-(His6)-cAbBCII10-CDR3/hCGBP3-sfGFP. The recombinant plasmids were transformed into E. coli BL21(DE3), and the fusion proteins were induced by IPTG. Highly soluble recombinant fusion proteins were obtained and purified by Ni-NTA affinity column. SDS-PAGE confirmed the purified protein as the target protein. The antigen-antibody binding assay showed that both the CDR1 and CDR3 grafted antibodies have hCG-binding activities. While the titers of the two grafted antibodies were similar, the binding affinity of CDR3 grafted antibody was higher than that of CDR1 grafted protein (about 2-3 times). The grafted antibodies retained the relatively high biochemical stability of the single-domain antibody backbone and were relatively thermostable and alkaline tolerant. The obtained antibodies also had a relatively high antigen-binding specificity to hCG. This study provided a reliable experimental basis for further optimization of anti-hCG single domain antibody by antibody grafting technology using antigen-binding peptide.

  1. Mechanism of Protein Denaturation: Partial Unfolding of the P22 Coat Protein I-Domain by Urea Binding.

    PubMed

    Newcomer, Rebecca L; Fraser, LaTasha C R; Teschke, Carolyn M; Alexandrescu, Andrei T

    2015-12-15

    The I-domain is an insertion domain of the bacteriophage P22 coat protein that drives rapid folding and accounts for over half of the stability of the full-length protein. We sought to determine the role of hydrogen bonds (H-bonds) in the unfolding of the I-domain by examining (3)JNC' couplings transmitted through H-bonds, the temperature and urea-concentration dependence of (1)HN and (15)N chemical shifts, and native-state hydrogen exchange at urea concentrations where the domain is predominantly folded. The native-state hydrogen-exchange data suggest that the six-stranded β-barrel core of the I-domain is more stable against unfolding than a smaller subdomain comprised of a short α-helix and three-stranded β-sheet. H-bonds, separately determined from solvent protection and (3)JNC' H-bond couplings, are identified with an accuracy of 90% by (1)HN temperature coefficients. The accuracy is improved to 95% when (15)N temperature coefficients are also included. In contrast, the urea dependence of (1)HN and (15)N chemical shifts is unrelated to H-bonding. The protein segments with the largest chemical-shift changes in the presence of urea show curved or sigmoidal titration curves suggestive of direct urea binding. Nuclear Overhauser effects to urea for these segments are also consistent with specific urea-binding sites in the I-domain. Taken together, the results support a mechanism of urea unfolding in which denaturant binds to distinct sites in the I-domain. Disordered segments bind urea more readily than regions in stable secondary structure. The locations of the putative urea-binding sites correlate with the lower stability of the structure against solvent exchange, suggesting that partial unfolding of the structure is related to urea accessibility. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Mechanism of Protein Denaturation: Partial Unfolding of the P22 Coat Protein I-Domain by Urea Binding

    PubMed Central

    Newcomer, Rebecca L.; Fraser, LaTasha C.R.; Teschke, Carolyn M.; Alexandrescu, Andrei T.

    2015-01-01

    The I-domain is an insertion domain of the bacteriophage P22 coat protein that drives rapid folding and accounts for over half of the stability of the full-length protein. We sought to determine the role of hydrogen bonds (H-bonds) in the unfolding of the I-domain by examining 3JNC’ couplings transmitted through H-bonds, the temperature and urea-concentration dependence of 1HN and 15N chemical shifts, and native-state hydrogen exchange at urea concentrations where the domain is predominantly folded. The native-state hydrogen-exchange data suggest that the six-stranded β-barrel core of the I-domain is more stable against unfolding than a smaller subdomain comprised of a short α-helix and three-stranded β-sheet. H-bonds, separately determined from solvent protection and 3JNC’ H-bond couplings, are identified with an accuracy of 90% by 1HN temperature coefficients. The accuracy is improved to 95% when 15N temperature coefficients are also included. In contrast, the urea dependence of 1HN and 15N chemical shifts is unrelated to H-bonding. The protein segments with the largest chemical-shift changes in the presence of urea show curved or sigmoidal titration curves suggestive of direct urea binding. Nuclear Overhauser effects to urea for these segments are also consistent with specific urea-binding sites in the I-domain. Taken together, the results support a mechanism of urea unfolding in which denaturant binds to distinct sites in the I-domain. Disordered segments bind urea more readily than regions in stable secondary structure. The locations of the putative urea-binding sites correlate with the lower stability of the structure against solvent exchange, suggesting that partial unfolding of the structure is related to urea accessibility. PMID:26682823

  3. Extrinsic pinning of magnetic domain walls in CoFeB-MgO nanowires with perpendicular anisotropy

    NASA Astrophysics Data System (ADS)

    Zhang, Xueying; Vernier, Nicolas; Zhao, Weisheng; Vila, Laurent; Ravelosona, Dafiné

    2018-05-01

    In this work, we have studied the mechanism of domain wall motion in 0.2-1.5 μm wide nanowires based on Ta/CoFeB/MgO films with perpendicular magnetic anisotropy. We show that domain wall propagation can be completely stopped due to the presence of strong pinning sites along the nanowires. From the analysis of the distribution of the strongest depinning fields as a function of the wire width, we evidence the presence of extrinsic pinning sites in nanowires, probably induced by edge damages, that dominate over the intrinsic pinning of the magnetic films even for these large wire widths.

  4. Structure of the C-terminal effector-binding domain of AhrC bound to its corepressor l-arginine

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

    Garnett, James A.; Baumberg, Simon; Stockley, Peter G.

    2007-11-01

    The crystal structure of the C-terminal domain hexameric core of AhrC, with bound corepressor (l-arginine), has been solved at 1.95 Å resolution. Binding of l-arginine results in a rotation between the two trimers of the hexamer, leading to the activation of the DNA-binding state. The arginine repressor/activator protein (AhrC) from Bacillus subtilis belongs to a large family of multifunctional transcription factors that are involved in the regulation of bacterial arginine metabolism. AhrC interacts with operator sites in the promoters of arginine biosynthetic and catabolic operons, acting as a transcriptional repressor at biosynthetic sites and an activator of transcription at catabolicmore » sites. AhrC is a hexamer of identical subunits, each having two domains. The C-terminal domains form the core of the protein and are involved in oligomerization and l-arginine binding. The N-terminal domains lie on the outside of the compact core and play a role in binding to 18 bp DNA operators called ARG boxes. The C-terminal domain of AhrC has been expressed, purified and characterized, and also crystallized as a hexamer with the bound corepressor l-arginine. Here, the crystal structure refined to 1.95 Å is presented.« less

  5. Biosensor-based approach identifies four distinct calmodulin-binding domains in the G protein-coupled estrogen receptor 1.

    PubMed

    Tran, Quang-Kim; Vermeer, Mark

    2014-01-01

    The G protein-coupled estrogen receptor 1 (GPER) has been demonstrated to participate in many cellular functions, but its regulatory inputs are not clearly understood. Here we describe a new approach that identifies GPER as a calmodulin-binding protein, locates interaction sites, and characterizes their binding properties. GPER coimmunoprecipitates with calmodulin in primary vascular smooth muscle cells under resting conditions, which is enhanced upon acute treatment with either specific ligands or a Ca(2+)-elevating agent. To confirm direct interaction and locate the calmodulin-binding domain(s), we designed a series of FRET biosensors that consist of enhanced cyan and yellow fluorescent proteins flanking each of GPER's submembrane domains (SMDs). Responses of these biosensors showed that all four submembrane domains directly bind calmodulin. Modifications of biosensor linker identified domains that display the strongest calmodulin-binding affinities and largest biosensor dynamics, including a.a. 83-93, 150-175, 242-259, 330-351, corresponding respectively to SMDs 1, 2, 3, and the juxta-membranous section of SMD4. These biosensors bind calmodulin in a strictly Ca(2+)-dependent fashion and with disparate affinities in the order SMD2>SMD4>SMD3>SMD1, apparent K d values being 0.44 ± 0.03, 1.40 ± 0.16, 8.01 ± 0.29, and 136.62 ± 6.56 µM, respectively. Interestingly, simultaneous determinations of biosensor responses and suitable Ca(2+) indicators identified separate Ca(2+) sensitivities for their interactions with calmodulin. SMD1-CaM complexes display a biphasic Ca(2+) response, representing two distinct species (SMD1 sp1 and SMD1 sp2) with drastically different Ca(2+) sensitivities. The Ca(2+) sensitivities of CaM-SMDs interactions follow the order SMD1sp1>SMD4>SMD2>SMD1sp2>SMD3, EC50(Ca(2+)) values being 0.13 ± 0.02, 0.75 ± 0.05, 2.38 ± 0.13, 3.71 ± 0.13, and 5.15 ± 0.25 µM, respectively. These data indicate that calmodulin may regulate GPER

  6. The HhH(2)/NDD Domain of the Drosophila Nod Chromokinesin-like Protein Is Required for Binding to Chromosomes in the Oocyte Nucleus

    PubMed Central

    Cui, Wei; Hawley, R. Scott

    2005-01-01

    Nod is a chromokinesin-like protein that plays a critical role in segregating achiasmate chromosomes during female meiosis. The C-terminal half of the Nod protein contains two putative DNA-binding domains. The first of these domains, known as the HMGN domain, consists of three tandemly repeated high-mobility group N motifs. This domain was previously shown to be both necessary and sufficient for binding of the C-terminal half of Nod to mitotic chromosomes in embryos. The second putative DNA-binding domain, denoted HhH(2)/NDD, is a helix-hairpin-helix(2)/Nod-like DNA-binding domain. Although the HhH(2)/NDD domain is not required or sufficient for chromosome binding in embryos, several well-characterized nod mutations have been mapped in this domain. To characterize the role of the HhH(2)/NDD domain in mediating Nod function, we created a series of UAS-driven transgene constructs capable of expressing either a wild-type Nod-GFP fusion protein or proteins in which the HhH(2)/NDD domain had been altered by site-directed mutagenesis. Although wild-type Nod-GFP localizes to the oocyte chromosomes and rescues the segregation defect in nod mutant oocytes, two of three proteins carrying mutants in the HhH(2)/NDD domain fail to either rescue the nod mutant phenotype or bind to oocyte chromosomes. However, these mutant proteins do bind to the polytene chromosomes in nurse-cell nuclei and enter the oocyte nucleus. Thus, even though the HhH(2)/NDD domain is not essential for chromosome binding in other cell types, it is required for chromosome binding in the oocyte. These HhH(2)/NDD mutants also block the localization of Nod to the posterior pole of stage 9–10A oocytes, a process that is thought to facilitate the interaction of Nod with the plus ends of microtubules (Cui et al. 2005). This observation suggests that the Nod HhH2/NDD domain may play other roles in addition to binding Nod to meiotic chromosomes. PMID:16143607

  7. Structural Basis and Function of XRN2-Binding by XTB Domains

    PubMed Central

    Richter, Hannes; Katic, Iskra; Gut, Heinz; Großhans, Helge

    2016-01-01

    The ribonuclease XRN2 is an essential player in RNA metabolism. In Caenorhabditis elegans, XRN2 functions with PAXT-1, which shares a putative XRN2-binding domain (XTBD) with otherwise unrelated mammalian proteins. Here, we characterize structure and function of an XTBD – XRN2 complex. Although XTBD stably interconnects two XRN2 domains through numerous interacting residues, mutation of a single critical residue suffices to disrupt XTBD – XRN2 complexes in vitro, and recapitulates paxt-1 null mutant phenotypes in vivo. Demonstrating conservation of function, vertebrate XTBD-containing proteins bind XRN2 in vitro, and human CDKN2AIPNL (C2AIL) can substitute for PAXT-1 in vivo. In vertebrates, where three distinct XTBD-containing proteins exist, XRN2 may partition to distinct stable heterodimeric complexes, likely differing in subcellular localization or function. In C. elegans, complex formation with the unique PAXT-1 serves to preserve the stability of XRN2 in the absence of substrate. PMID:26779609

  8. SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family

    PubMed Central

    2010-01-01

    Background Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. Findings De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Conclusions Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein. PMID:20979600

  9. Kinesin-1 and mitochondrial motility control by discrimination of structurally equivalent but distinct subdomains in Ran-GTP-binding domains of Ran-binding protein 2.

    PubMed

    Patil, Hemangi; Cho, Kyoung-in; Lee, James; Yang, Yi; Orry, Andrew; Ferreira, Paulo A

    2013-03-27

    The pleckstrin homology (PH) domain is a versatile fold that mediates a variety of protein-protein and protein-phosphatidylinositol lipid interactions. The Ran-binding protein 2 (RanBP2) contains four interspersed Ran GTPase-binding domains (RBD(n = 1-4)) with close structural homology to the PH domain of Bruton's tyrosine kinase. The RBD2, kinesin-binding domain (KBD) and RBD3 comprise a tripartite domain (R2KR3) of RanBP2 that causes the unfolding, microtubule binding and biphasic activation of kinesin-1, a crucial anterograde motor of mitochondrial motility. However, the interplay between Ran GTPase and R2KR3 of RanBP2 in kinesin-1 activation and mitochondrial motility is elusive. We use structure-function, biochemical, kinetic and cell-based assays with time-lapse live-cell microscopy of over 260,000 mitochondrial-motility-related events to find mutually exclusive subdomains in RBD2 and RBD3 towards Ran GTPase binding, kinesin-1 activation and mitochondrial motility regulation. The RBD2 and RBD3 exhibit Ran-GTP-independent, subdomain and stereochemical-dependent discrimination on the biphasic kinetics of kinesin-1 activation or regulation of mitochondrial motility. Further, KBD alone and R2KR3 stimulate and suppress, respectively, multiple biophysical parameters of mitochondrial motility. The regulation of the bidirectional transport of mitochondria by either KBD or R2KR3 is highly coordinated, because their kinetic effects are accompanied always by changes in mitochondrial motile events of either transport polarity. These studies uncover novel roles in Ran GTPase-independent subdomains of RBD2 and RBD3, and KBD of RanBP2, that confer antagonizing and multi-modal mechanisms of kinesin-1 activation and regulation of mitochondrial motility. These findings open new venues towards the pharmacological harnessing of cooperative and competitive mechanisms regulating kinesins, RanBP2 or mitochondrial motility in disparate human disorders.

  10. Domain wall oscillation in magnetic nanowire with a geometrically confined region

    NASA Astrophysics Data System (ADS)

    Sbiaa, R.; Bahri, M. Al; Piramanayagam, S. N.

    2018-06-01

    In conventional magnetic devices such as magnetic tunnel junctions, a steady oscillation of a soft layer magnetization could find its application in various electronic systems. However, these devices suffer from their low output signal and large spectral linewidth. A more elegant scheme based on domain wall oscillation could be a solution to these issues if DW dynamics could be controlled precisely in space and time. In fact, in DW devices, the magnetic configuration of domain wall and its position are strongly dependent on the device geometry and material properties. Here we show that in a constricted device with judiciously adjusted dimensions, a DW can be trapped within the central part and keep oscillating with a single frequency f. For 200 nm by 40 nm nanowire, f was found to vary from 2 GHz to 3 GHz for a current density between 4.8 × 1012 A/m2 and 5.6 × 1012 A/m2. More interestingly, the device fabrication is simply based on two long nanowires connected by adjusting the offset in both x and y directions. This new type of devices enables the conversion of dc-current to an ac-voltage in a controllable manner opening thus the possibility of a new nano-oscillators with better performance.

  11. Conserved Receptor-Binding Domains of Lake Victoria Marburgvirus and Zaire Ebolavirus Bind a Shared Receptor

    DTIC Science & Technology

    2006-04-14

    virion, because of the functional importance of and limited variation in this region (44, 45). In some cases, such as murine and feline leukemia viruses ...murine leukemia virus ; PBS, phos- phate-buffered saline; RBD, receptor-binding domain; SARS, severe acute respiratory syndrome; VSV, vesicular stomatitis...entryofpseudotypedret- roviruses. A Moloney murine leukemia virus vector expressing GFP was pseudotyped with the GP1,2 of MARV-Mus (MARV/MLV), a mucin-like

  12. Analysis of the hormone-binding domain of steroid receptors using chimeras generated by homologous recombination

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

    Martinez, Elisabeth D.; Pattabiraman, Nagarajan; Department of Oncology, Georgetown University School of Medicine, Washington, DC 20057

    2005-08-15

    The glucocorticoid receptor and the mineralocorticoid receptor are members of the steroid receptor family that exhibit ligand cross-reactivity. Specificity of steroid receptor action is investigated in the present work by the construction and characterization of chimeras between the glucocorticoid receptor and the mineralocorticoid receptor. We used an innovative approach to make novel steroid receptor proteins in vivo that in general, contrary to our expectations, show increased ligand specificity compared to the parental receptors. We describe a receptor that is specific for the potent synthetic glucocorticoid triamcinolone acetonide and does not bind aldosterone. A further set of chimeras has an increasedmore » ability to discriminate between ligands, responding potently to mineralocorticoids and only very weakly to synthetic glucocorticoids. A chimera with the fusion site in the hinge highlights the importance of the region between the DNA-binding and the hormone-binding domains since, unlike both the glucocorticoid and mineralocorticoid receptors, it only responds to mineralocorticoids. One chimera has reduced specificity in that it acts as a general corticoid receptor, responding to glucocorticoids and mineralocorticoids with similar potency and efficacy. Our data suggest that regions of the glucocorticoid and mineralocorticoid receptor hormone-binding domains are functionally non-reciprocal. We present transcriptional, hormone-binding, and structure-modeling evidence that suggests that receptor-specific interactions within and across domains mediate aspects of specificity in transcriptional responses to steroids.« less

  13. Mapping EBNA-1 Domains Involved in Binding to Metaphase Chromosomes

    PubMed Central

    Marechal, Vincent; Dehee, Axelle; Chikhi-Brachet, Roxane; Piolot, Tristan; Coppey-Moisan, Maité; Nicolas, Jean-Claude

    1999-01-01

    The Epstein-Barr virus (EBV) genome can persist in dividing human B cells as multicopy circular episomes. Viral episomes replicate in synchrony with host cell DNA and are maintained at a relatively constant copy number for a long time. Only two viral elements, the replication origin OriP and the EBNA-1 protein, are required for the persistence of viral genomes during latency. EBNA-1 activates OriP during the S phase and may also contribute to the partition and/or retention of viral genomes during mitosis. Indeed, EBNA-1 has been shown to interact with mitotic chromatin. Moreover, viral genomes are noncovalently associated with metaphase chromosomes. This suggests that EBNA-1 may facilitate the anchorage of viral genomes on cellular chromosomes, thus ensuring proper partition and retention. In the present paper, we have investigated the chromosome-binding activity of EBV EBNA-1, herpesvirus papio (HVP) EBNA-1, and various derivatives of EBV EBNA-1, fused to a variant of the green fluorescent protein. The results show that binding to metaphase chromosomes is a common property of EBV and HVP EBNA-1. Further studies indicated that at least three independent domains (CBS-1, -2, and -3) mediate EBNA-1 binding to metaphase chromosomes. In agreement with the anchorage model, two of these domains mapped to a region that has been previously demonstrated to be required for the long-term persistence of OriP-containing plasmids. PMID:10196336

  14. WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer.

    PubMed

    Chen, Shuai; Wang, Han; Huang, Yu-Fan; Li, Ming-Li; Cheng, Jiang-Hong; Hu, Peng; Lu, Chuan-Hui; Zhang, Ya; Liu, Na; Tzeng, Chi-Meng; Zhang, Zhi-Ming

    2017-07-19

    The WW domain is composed of 38 to 40 semi-conserved amino acids shared with structural, regulatory, and signaling proteins. WW domain-binding protein 2 (WBP2), as a binding partner of WW domain protein, interacts with several WW-domain-containing proteins, such as Yes kinase-associated protein (Yap), paired box gene 8 (Pax8), WW-domain-containing transcription regulator protein 1 (TAZ), and WW-domain-containing oxidoreductase (WWOX) through its PPxY motifs within C-terminal region, and further triggers the downstream signaling pathway in vitro and in vivo. Studies have confirmed that phosphorylated form of WBP2 can move into nuclei and activate the transcription of estrogen receptor (ER) and progesterone receptor (PR), whose expression were the indicators of breast cancer development, indicating that WBP2 may participate in the progression of breast cancer. Both overexpression of WBP2 and activation of tyrosine phosphorylation upregulate the signal cascades in the cross-regulation of the Wnt and ER signaling pathways in breast cancer. Following the binding of WBP2 to the WW domain region of TAZ which can accelerate migration, invasion and is required for the transformed phenotypes of breast cancer cells, the transformation of epithelial to mesenchymal of MCF10A is activated, suggesting that WBP2 is a key player in regulating cell migration. When WBP2 binds with WWOX, a tumor suppressor, ER transactivation and tumor growth can be suppressed. Thus, WBP2 may serve as a molecular on/off switch that controls the crosstalk between E2, WWOX, Wnt, TAZ, and other oncogenic signaling pathways. This review interprets the relationship between WBP2 and breast cancer, and provides comprehensive views about the function of WBP2 in the regulation of the pathogenesis of breast cancer and endocrine therapy in breast cancer treatment.

  15. Gravitational domain walls and the dynamics of the gravitational constant G

    NASA Astrophysics Data System (ADS)

    Bunster, Claudio; Gomberoff, Andrés

    2017-07-01

    From the point of view of elementary particle physics, the gravitational constant G is extraordinarily small. This has led to asking whether it could have decayed to its present value from an initial one commensurate with microscopical units. A mechanism that leads to such a decay is proposed herein. It is based on assuming that G may take different values within regions of the universe separated by a novel kind of domain wall, a "G -wall." The idea is implemented by introducing a gauge potential Aμ ν ρ, and its conjugate D , which determines the value of G as an integration constant rather than a fundamental constant. The value of G jumps when one goes through a G -wall. The procedure extends one previously developed for the cosmological constant, but the generalization is far from straightforward: (i) The intrinsic geometry of a G -wall is not the same as seen from its two sides because the second law of black hole thermodynamics mandates that the jump in G must cause a discontinuity in the scale of length. (ii) The size of the decay step in G is controlled by a function G (D ) which may be chosen so as to diminish the value of G towards the asymptote G =0 . It is shown that: (i) The dynamics of the gravitational field with G treated as a dynamical variable, coupled to G -walls and matter, follows from an action principle, which is given. (ii) A particle that impinges on a G -wall may be refracted or reflected. (iii) The various forces between two particles change when a G -wall is inserted in between them. (iv) G -walls may be nucleated trough tunneling and thermal effects, whose semiclassical probabilities are evaluated. (v) If the action principle is constructed properly, the entropy of a black hole increases when the value of the gravitational constant is changed through the absorption of a G-wall by the hole.

  16. Methods of detection using a cellulose binding domain fusion product

    DOEpatents

    Shoseyov, O.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1999-01-05

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 34 figs.

  17. Methods of detection using a cellulose binding domain fusion product

    DOEpatents

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1999-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  18. Structural and mutational analyses of the receptor binding domain of botulinum D/C mosaic neurotoxin: Insight into the ganglioside binding mechanism

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

    Nuemket, Nipawan; Tanaka, Yoshikazu; Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810

    2011-07-29

    Highlights: {yields} We determined the crystal structure of the receptor binding domain of BoNT in complex with 3'-sialyllactose. {yields} An electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. {yields} Alanine site-directed mutagenesis showed that GBS and GBL are important for ganglioside binding. {yields} A cell binding mechanism, which involves cooperative contribution of two sites, was proposed. -- Abstract: Clostridium botulinum type D strain OFD05, which produces the D/C mosaic neurotoxin, was isolated from cattle killed by the recent botulism outbreak in Japan. The D/C mosaic neurotoxin is the most toxic of the botulinummore » neurotoxins (BoNT) characterized to date. Here, we determined the crystal structure of the receptor binding domain of BoNT from strain OFD05 in complex with 3'-sialyllactose at a resolution of 3.0 A. In the structure, an electron density derived from the 3'-sialyllactose was confirmed at the cleft in the C-terminal subdomain. Alanine site-directed mutagenesis showed the significant contribution of the residues surrounding the cleft to ganglioside recognition. In addition, a loop adjoining the cleft also plays an important role in ganglioside recognition. In contrast, little effect was observed when the residues located around the surface previously identified as the protein receptor binding site in other BoNTs were substituted. The results of cell binding analysis of the mutants were significantly correlated with the ganglioside binding properties. Based on these observations, a cell binding mechanism of BoNT from strain OFD05 is proposed, which involves cooperative contribution of two ganglioside binding sites.« less

  19. Takifugu rubripes cation independent mannose 6-phosphate receptor: Cloning, expression and functional characterization of the IGF-II binding domain.

    PubMed

    A, Ajith Kumar; Nadimpalli, Siva Kumar

    2018-07-01

    Mannose 6-phosphate/IGF-II receptor mediated lysosomal clearance of insulin-like growth factor-II is significantly associated with the evolution of placental mammals. The protein is also referred to as the IGF-II receptor. Earlier studies suggested relatively low binding affinity between the receptor and ligand in prototherian and metatherian mammals. In the present study, we cloned the IGF-II binding domain of the early vertebrate fugu fish and expressed it in bacteria. A 72000Da truncated receptor containing the IGF-II binding domain was obtained. Analysis of this protein (covering domains 11-13 of the CIMPR) for its affinity to fish and human IGF-II by ligand blot assays and ELISA showed that the expressed receptor can specifically bind to both fish and human IGF-II. Additionally, a peptide-specific antibody raised against the region of the IGF-II binding domain also was able to recognize the IGF-II binding regions of mammalian and non-mammalian cation independent MPR protein. These interactions were further characterized by Surface Plasma resonance support that the receptor binds to fish IGF-II, with a dissociation constant of 548nM. Preliminary analysis suggests that the binding mechanism as well as the affinity of the fish and human receptor for IGF-II may have varied according to different evolutionary pressures. Copyright © 2018. Published by Elsevier B.V.

  20. In silico screening for inhibitors of p-glycoprotein that target the nucleotide binding domains.

    PubMed

    Brewer, Frances K; Follit, Courtney A; Vogel, Pia D; Wise, John G

    2014-12-01

    Multidrug resistances and the failure of chemotherapies are often caused by the expression or overexpression of ATP-binding cassette transporter proteins such as the multidrug resistance protein, P-glycoprotein (P-gp). P-gp is expressed in the plasma membrane of many cell types and protects cells from accumulation of toxins. P-gp uses ATP hydrolysis to catalyze the transport of a broad range of mostly hydrophobic compounds across the plasma membrane and out of the cell. During cancer chemotherapy, the administration of therapeutics often selects for cells which overexpress P-gp, thereby creating populations of cancer cells resistant to a variety of chemically unrelated chemotherapeutics. The present study describes extremely high-throughput, massively parallel in silico ligand docking studies aimed at identifying reversible inhibitors of ATP hydrolysis that target the nucleotide-binding domains of P-gp. We used a structural model of human P-gp that we obtained from molecular dynamics experiments as the protein target for ligand docking. We employed a novel approach of subtractive docking experiments that identified ligands that bound predominantly to the nucleotide-binding domains but not the drug-binding domains of P-gp. Four compounds were found that inhibit ATP hydrolysis by P-gp. Using electron spin resonance spectroscopy, we showed that at least three of these compounds affected nucleotide binding to the transporter. These studies represent a successful proof of principle demonstrating the potential of targeted approaches for identifying specific inhibitors of P-gp. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.