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Sample records for compo composite motif

  1. Composite Materials Processing of Cast Iron and Ceramics Using Compo-Casting Technology

    NASA Astrophysics Data System (ADS)

    Tomita, Yoshihiro; Sumimoto, Haruyoshi

    The compo-casting technology of ceramics and cast iron is expected to be one of the major casting technologies that can expand the application fields of cast iron. This technique allows the heat energy of the molten metal to be utilized to produce cast iron products which are added with functions of ceramic materials. The largest problem in compo-casting technology is generation of cracks caused by thermal shock. Although this crack generation can be prevented by reducing the thermal stress by means of preheating ceramics, the necessary preheating temperature is considerably high and its precise controlling is difficult at the practical foundry working sites. In this study, we tried to numerically predict the critical preheating temperature of ceramics using the thermal stress analysis in unsteady heat transfer and the Newman's diagram, and found that the preheating of ceramics to reduce thermal stress could be substituted with placing an appropriate cast iron cover around the ceramics. Excellent results were obtained by using a method whereby a ceramic bar was covered with a flake graphite cast iron cover and fixed in a sand mold and then molten metal was poured. Then, two or three ceramics were examined at the same time under the compocasting condition. As a result, three specimens could be done at the same time by adjusting the cover space to 15mm. Moreover, irregular shape ceramics were examined under the compocasting condition. As a result, the compocasting could be done by devising the cover shape. In each condition, it was confirmed that the cover shape made from the analytical result was effective to the compocasting by doing the thermometry of the specimens.

  2. Factoring local sequence composition in motif significance analysis.

    PubMed

    Ng, Patrick; Keich, Uri

    2008-01-01

    We recently introduced a biologically realistic and reliable significance analysis of the output of a popular class of motif finders. In this paper we further improve our significance analysis by incorporating local base composition information. Relying on realistic biological data simulation, as well as on FDR analysis applied to real data, we show that our method is significantly better than the increasingly popular practice of using the normal approximation to estimate the significance of a finder's output. Finally we turn to leveraging our reliable significance analysis to improve the actual motif finding task. Specifically, endowing a variant of the Gibbs Sampler with our improved significance analysis we demonstrate that de novo finders can perform better than has been perceived. Significantly, our new variant outperforms all the finders reviewed in a recently published comprehensive analysis of the Harbison genome-wide binding location data. Interestingly, many of these finders incorporate additional information such as nucleosome positioning and the significance of binding data.

  3. Motif types, motif locations and base composition patterns around the RNA polyadenylation site in microorganisms, plants and animals

    PubMed Central

    2014-01-01

    Background The polyadenylation of RNA is critical for gene functioning, but the conserved sequence motifs (often called signal or signature motifs), motif locations and abundances, and base composition patterns around mRNA polyadenylation [poly(A)] sites are still uncharacterized in most species. The evolutionary tendency for poly(A) site selection is still largely unknown. Results We analyzed the poly(A) site regions of 31 species or phyla. Different groups of species showed different poly(A) signal motifs: UUACUU at the poly(A) site in the parasite Trypanosoma cruzi; UGUAAC (approximately 13 bases upstream of the site) in the alga Chlamydomonas reinhardtii; UGUUUG (or UGUUUGUU) at mainly the fourth base downstream of the poly(A) site in the parasite Blastocystis hominis; and AAUAAA at approximately 16 bases and approximately 19 bases upstream of the poly(A) site in animals and plants, respectively. Polyadenylation signal motifs are usually several hundred times more abundant around poly(A) sites than in whole genomes. These predominant motifs usually had very specific locations, whether upstream of, at, or downstream of poly(A) sites, depending on the species or phylum. The poly(A) site was usually an adenosine (A) in all analyzed species except for B. hominis, and there was weak A predominance in C. reinhardtii. Fungi, animals, plants, and the protist Phytophthora infestans shared a general base abundance pattern (or base composition pattern) of “U-rich—A-rich—U-rich—Poly(A) site—U-rich regions”, or U-A-U-A-U for short, with some variation for each kingdom or subkingdom. Conclusion This study identified the poly(A) signal motifs, motif locations, and base composition patterns around mRNA poly(A) sites in protists, fungi, plants, and animals and provided insight into poly(A) site evolution. PMID:25052519

  4. Composition of the Hemagglutinin Polybasic Proteolytic Cleavage Motif Mediates Variable Virulence of H7N7 Avian Influenza Viruses

    PubMed Central

    Abdelwhab, E. M.; Veits, Jutta; Ulrich, Reiner; Kasbohm, Elisa; Teifke, Jens P.; Mettenleiter, Thomas C.

    2016-01-01

    Acquisition of a polybasic cleavage site (pCS) in the hemagglutinin (HA) is a prerequisite for the shift of low pathogenic (LP) avian influenza virus (AIV) to the highly pathogenic (HP) form in chickens. Whereas presence of a pCS is required for high pathogenicity, less is known about the effect of composition of pCS on virulence of AIV particularly H7N7. Here, we investigated the virulence of four avian H7N7 viruses after insertion of different naturally occurring pCS from two HPAIV H7N7 (designated pCSGE and pCSUK) or from H7N1 (pCSIT). In vitro, the different pCS motifs modulated viral replication and the HA cleavability independent on the HA background. However, in vivo, the level of virulence conferred by the different pCS varied significantly. Within the respective viral backgrounds viruses with pCSIT and pCSGE were more virulent than those coding for pCSUK. The latter showed also the most restricted spread in inoculated birds. Besides the pCS, other gene segments modulated virulence of these H7N7 viruses. Together, the specific composition of the pCS significantly influences virulence of H7N7 viruses. Eurasian LPAIV H7N7 may shift to high pathogenicity after acquisition of “specific” pCS motifs and/or other gene segments from HPAIV. PMID:28004772

  5. Precision Composite Space Structures

    DTIC Science & Technology

    2007-10-15

    analysis of composite laminates with bolted joints under bending loads. J Compos Mater 1995;29(1):15-36. 283 [D.52]. Lee JD. Three dimensional...fiber reinforced composite bends . J Compos Mater 1986;20(1):30-45. [D.57]. Nagesh. Finite-element analysis of pressure vessels with progressive...composite cylinder subjected to three-point bending : Correlation of beam theory with experiment. Compos Struct 2004;63(3-4):439-445. [D.135]. Huang ZM

  6. Skin grafting in severely contracted socket with the use of 'Compo'.

    PubMed

    Betharia, S M; Kanthamani; Prakash, H; Kumar, S

    1990-01-01

    The results of split thickness autologous skin grafting along with the use of a dental impression material (Compo), a thermoplastic substance are presented in a series of 11 patients of acquired, severely contracted, anophthalmic sockets. Only the fornix fixation sutures and the central tarsorrhaphy were employed for the proper placement of graft without the use of retention devices. Artificial eyes were successfully fitted and retained subsequently after 6 weeks of grafting.

  7. Composite Conserved Promoter–Terminator Motifs (PeSLs) that Mediate Modular Shuffling in the Diverse T4-Like Myoviruses

    PubMed Central

    Comeau, André M.; Arbiol, Christine; Krisch, Henry M.

    2014-01-01

    The diverse T4-like phages (Tquatrovirinae) infect a wide array of gram-negative bacterial hosts. The genome architecture of these phages is generally well conserved, most of the phylogenetically variable genes being grouped together in a series hyperplastic regions (HPRs) that are interspersed among large blocks of conserved core genes. Recent evidence from a pair of closely related T4-like phages has suggested that small, composite terminator/promoter sequences (promoterearly stem loop [PeSLs]) were implicated in mediating the high levels of genetic plasticity by indels occurring within the HPRs. Here, we present the genome sequence analysis of two T4-like phages, PST (168 kb, 272 open reading frames [ORFs]) and nt-1 (248 kb, 405 ORFs). These two phages were chosen for comparative sequence analysis because, although they are closely related to phages that have been previously sequenced (T4 and KVP40, respectively), they have different host ranges. In each case, one member of the pair infects a bacterial strain that is a human pathogen, whereas the other phage’s host is a nonpathogen. Despite belonging to phylogenetically distant branches of the T4-likes, these pairs of phage have diverged from each other in part by a mechanism apparently involving PeSL-mediated recombination. This analysis confirms a role of PeSL sequences in the generation of genomic diversity by serving as a point of genetic exchange between otherwise unrelated sequences within the HPRs. Finally, the palette of divergent genes swapped by PeSL-mediated homologous recombination is discussed in the context of the PeSLs’ potentially important role in facilitating phage adaption to new hosts and environments. PMID:24951563

  8. The Motif of Meeting in Digital Education

    ERIC Educational Resources Information Center

    Sheail, Philippa

    2015-01-01

    This article draws on theoretical work which considers the composition of meetings, in order to think about the form of the meeting in digital environments for higher education. To explore the motif of meeting, I undertake a "compositional interpretation" (Rose, 2012) of the default interface offered by "Collaborate", an…

  9. Genome editing with CompoZr custom zinc finger nucleases (ZFNs).

    PubMed

    Hansen, Keith; Coussens, Matthew J; Sago, Jack; Subramanian, Shilpi; Gjoka, Monika; Briner, Dave

    2012-06-14

    Genome editing is a powerful technique that can be used to elucidate gene function and the genetic basis of disease. Traditional gene editing methods such as chemical-based mutagenesis or random integration of DNA sequences confer indiscriminate genetic changes in an overall inefficient manner and require incorporation of undesirable synthetic sequences or use of aberrant culture conditions, potentially confusing biological study. By contrast, transient ZFN expression in a cell can facilitate precise, heritable gene editing in a highly efficient manner without the need for administration of chemicals or integration of synthetic transgenes. Zinc finger nucleases (ZFNs) are enzymes which bind and cut distinct sequences of double-stranded DNA (dsDNA). A functional CompoZr ZFN unit consists of two individual monomeric proteins that bind a DNA "half-site" of approximately 15-18 nucleotides (see Figure 1). When two ZFN monomers "home" to their adjacent target sites the DNA-cleavage domains dimerize and create a double-strand break (DSB) in the DNA. Introduction of ZFN-mediated DSBs in the genome lays a foundation for highly efficient genome editing. Imperfect repair of DSBs in a cell via the non-homologous end-joining (NHEJ) DNA repair pathway can result in small insertions and deletions (indels). Creation of indels within the gene coding sequence of a cell can result in frameshift and subsequent functional knockout of a gene locus at high efficiency. While this protocol describes the use of ZFNs to create a gene knockout, integration of transgenes may also be conducted via homology-directed repair at the ZFN cut site. The CompoZr Custom ZFN Service represents a systematic, comprehensive, and well-characterized approach to targeted gene editing for the scientific community with ZFN technology. Sigma scientists work closely with investigators to 1) perform due diligence analysis including analysis of relevant gene structure, biology, and model system pursuant to the

  10. Protospacer recognition motifs

    PubMed Central

    Shah, Shiraz A.; Erdmann, Susanne; Mojica, Francisco J.M.; Garrett, Roger A.

    2013-01-01

    Protospacer adjacent motifs (PAMs) were originally characterized for CRISPR-Cas systems that were classified on the basis of their CRISPR repeat sequences. A few short 2–5 bp sequences were identified adjacent to one end of the protospacers. Experimental and bioinformatical results linked the motif to the excision of protospacers and their insertion into CRISPR loci. Subsequently, evidence accumulated from different virus- and plasmid-targeting assays, suggesting that these motifs were also recognized during DNA interference, at least for the recently classified type I and type II CRISPR-based systems. The two processes, spacer acquisition and protospacer interference, employ different molecular mechanisms, and there is increasing evidence to suggest that the sequence motifs that are recognized, while overlapping, are unlikely to be identical. In this article, we consider the properties of PAM sequences and summarize the evidence for their dual functional roles. It is proposed to use the terms protospacer associated motif (PAM) for the conserved DNA sequence and to employ spacer acqusition motif (SAM) and target interference motif (TIM), respectively, for acquisition and interference recognition sites. PMID:23403393

  11. Motif enrichment tool.

    PubMed

    Blatti, Charles; Sinha, Saurabh

    2014-07-01

    The Motif Enrichment Tool (MET) provides an online interface that enables users to find major transcriptional regulators of their gene sets of interest. MET searches the appropriate regulatory region around each gene and identifies which transcription factor DNA-binding specificities (motifs) are statistically overrepresented. Motif enrichment analysis is currently available for many metazoan species including human, mouse, fruit fly, planaria and flowering plants. MET also leverages high-throughput experimental data such as ChIP-seq and DNase-seq from ENCODE and ModENCODE to identify the regulatory targets of a transcription factor with greater precision. The results from MET are produced in real time and are linked to a genome browser for easy follow-up analysis. Use of the web tool is free and open to all, and there is no login requirement. ADDRESS: http://veda.cs.uiuc.edu/MET/.

  12. Seeing the B-A-C-H motif

    NASA Astrophysics Data System (ADS)

    Catravas, Palmyra

    2005-09-01

    Musical compositions can be thought of as complex, multidimensional data sets. Compositions based on the B-A-C-H motif (a four-note motif of the pitches of the last name of Johann Sebastian Bach) span several centuries of evolving compositional styles and provide an intriguing set for analysis since they contain a common feature, the motif, buried in dissimilar contexts. We will present analyses which highlight the content of this unusual set of pieces, with emphasis on visual display of information.

  13. [Personal motif in art].

    PubMed

    Gerevich, József

    2015-01-01

    One of the basic questions of the art psychology is whether a personal motif is to be found behind works of art and if so, how openly or indirectly it appears in the work itself. Analysis of examples and documents from the fine arts and literature allow us to conclude that the personal motif that can be identified by the viewer through symbols, at times easily at others with more difficulty, gives an emotional plus to the artistic product. The personal motif may be found in traumatic experiences, in communication to the model or with other emotionally important persons (mourning, disappointment, revenge, hatred, rivalry, revolt etc.), in self-searching, or self-analysis. The emotions are expressed in artistic activity either directly or indirectly. The intention nourished by the artist's identity (Kunstwollen) may stand in the way of spontaneous self-expression, channelling it into hidden paths. Under the influence of certain circumstances, the artist may arouse in the viewer, consciously or unconsciously, an illusionary, misleading image of himself. An examination of the personal motif is one of the important research areas of art therapy.

  14. Convergent evolution and mimicry of protein linear motifs in host-pathogen interactions.

    PubMed

    Chemes, Lucía Beatriz; de Prat-Gay, Gonzalo; Sánchez, Ignacio Enrique

    2015-06-01

    Pathogen linear motif mimics are highly evolvable elements that facilitate rewiring of host protein interaction networks. Host linear motifs and pathogen mimics differ in sequence, leading to thermodynamic and structural differences in the resulting protein-protein interactions. Moreover, the functional output of a mimic depends on the motif and domain repertoire of the pathogen protein. Regulatory evolution mediated by linear motifs can be understood by measuring evolutionary rates, quantifying positive and negative selection and performing phylogenetic reconstructions of linear motif natural history. Convergent evolution of linear motif mimics is widespread among unrelated proteins from viral, prokaryotic and eukaryotic pathogens and can also take place within individual protein phylogenies. Statistics, biochemistry and laboratory models of infection link pathogen linear motifs to phenotypic traits such as tropism, virulence and oncogenicity. In vitro evolution experiments and analysis of natural sequences suggest that changes in linear motif composition underlie pathogen adaptation to a changing environment.

  15. Cell-specific expression of the macrophage scavenger receptor gene is dependent on PU.1 and a composite AP-1/ets motif.

    PubMed Central

    Moulton, K S; Semple, K; Wu, H; Glass, C K

    1994-01-01

    The type I and II scavenger receptors (SRs) are highly restricted to cells of monocyte origin and become maximally expressed during the process of monocyte-to-macrophage differentiation. In this report, we present evidence that SR genomic sequences from -245 to +46 bp relative to the major transcriptional start site were sufficient to confer preferential expression of a reporter gene to cells of monocyte and macrophage origin. This profile of expression resulted from the combinatorial actions of multiple positive and negative regulatory elements. Positive transcriptional control was primarily determined by two elements, located 181 and 46 bp upstream of the major transcriptional start site. Transcriptional control via the -181 element was mediated by PU.1/Spi-1, a macrophage and B-cell-specific transcription factor that is a member of the ets domain gene family. Intriguingly, the -181 element represented a relatively low-affinity binding site for Spi-B, a closely related member of the ets domain family that has been shown to bind with relatively high affinity to other PU.1/Spi-1 binding sites. These observations support the idea that PU.1/Spi-1 and Spi-B regulate overlapping but nonidentical sets of genes. The -46 element represented a composite binding site for a distinct set of ets domain proteins that were preferentially expressed in monocyte and macrophage cell lines and that formed ternary complexes with members of the AP-1 gene family. In concert, these observations suggest a model for how interactions between cell-specific and more generally expressed transcription factors function to dictate the appropriate temporal and cell-specific patterns of SR expression during the process of macrophage differentiation. Images PMID:8007948

  16. Germination et texture du composé supraconducteur Nb3Sn

    NASA Astrophysics Data System (ADS)

    Taillard, R.; Ustinov, A. I.

    2002-07-01

    The composite design and/or manufacturing process of the Nb3Sn multifilamentary strands are continuously changed so as to improve the superconducting behaviour. Such an enhancement depends on both the amount and microstructure of the superconducting phase. The study of the parameters and of the mechanisms of the phase transformations is therefore of the higher importance. The stages of nucleation and growth of the Nb3Sn grains are mainly investigated by thin foil transmission electron microscopy and by X-ray diffraction. The results obtained with the various techniques are shown to be in accordance and to complete each other. An example establishes their usefulness in order to explain the evolution of the critical current density. The effect of the grain misorientation on the critical current density is also considered. L'amélioration du comportement supraconducteur des composites multifilantentaires à base de Nb3Sn passe par la définition de nouveaux designs et/ou de nouveaux procédés de fabrication. Le comportement supraconducteur est régi par la quantité et la microstructure de la phase supraconductrice. Ce dernier paramètre impose d'identifier la nature des mécanismes des transformations de phases et leurs paramèt res. La démarche met en oeuvre la microscopie électronique en transmission et la détermination des orientations cristallographiques aux rayons X. Elle est appliquée aux stades de germination et de croissance des grains de la phase Nb3Sn dans le procédé de la source d'étain interne. Les apports complémentaires et concordants des différentes techniques sont dégagés. L'importance des résultats pour l'interprétation des variations de la densité de courant critique est démontrée par un exemple. L'influence de la désorientation entre les grains sur la densité de courant critique est finalement considérée.

  17. MISCORE: a new scoring function for characterizing DNA regulatory motifs in promoter sequences

    PubMed Central

    2012-01-01

    Background Computational approaches for finding DNA regulatory motifs in promoter sequences are useful to biologists in terms of reducing the experimental costs and speeding up the discovery process of de novo binding sites. It is important for rule-based or clustering-based motif searching schemes to effectively and efficiently evaluate the similarity between a k-mer (a k-length subsequence) and a motif model, without assuming the independence of nucleotides in motif models or without employing computationally expensive Markov chain models to estimate the background probabilities of k-mers. Also, it is interesting and beneficial to use a priori knowledge in developing advanced searching tools. Results This paper presents a new scoring function, termed as MISCORE, for functional motif characterization and evaluation. Our MISCORE is free from: (i) any assumption on model dependency; and (ii) the use of Markov chain model for background modeling. It integrates the compositional complexity of motif instances into the function. Performance evaluations with comparison to the well-known Maximum a Posteriori (MAP) score and Information Content (IC) have shown that MISCORE has promising capabilities to separate and recognize functional DNA motifs and its instances from non-functional ones. Conclusions MISCORE is a fast computational tool for candidate motif characterization, evaluation and selection. It enables to embed priori known motif models for computing motif-to-motif similarity, which is more advantageous than IC and MAP score. In addition to these merits mentioned above, MISCORE can automatically filter out some repetitive k-mers from a motif model due to the introduction of the compositional complexity in the function. Consequently, the merits of our proposed MISCORE in terms of both motif signal modeling power and computational efficiency will make it more applicable in the development of computational motif discovery tools. PMID:23282090

  18. Motif Yggdrasil: sampling sequence motifs from a tree mixture model.

    PubMed

    Andersson, Samuel A; Lagergren, Jens

    2007-06-01

    In phylogenetic foot-printing, putative regulatory elements are found in upstream regions of orthologous genes by searching for common motifs. Motifs in different upstream sequences are subject to mutations along the edges of the corresponding phylogenetic tree, consequently taking advantage of the tree in the motif search is an appealing idea. We describe the Motif Yggdrasil sampler; the first Gibbs sampler based on a general tree that uses unaligned sequences. Previous tree-based Gibbs samplers have assumed a star-shaped tree or partially aligned upstream regions. We give a probabilistic model (MY model) describing upstream sequences with regulatory elements and build a Gibbs sampler with respect to this model. The model allows toggling, i.e., the restriction of a position to a subset of nucleotides, but does not require aligned sequences nor edge lengths, which may be difficult to come by. We apply the collapsing technique to eliminate the need to sample nuisance parameters, and give a derivation of the predictive update formula. We show that the MY model improves the modeling of difficult motif instances and that the use of the tree achieves a substantial increase in nucleotide level correlation coefficient both for synthetic data and 37 bacterial lexA genes. We investigate the sensitivity to errors in the tree and show that using random trees MY sampler still has a performance similar to the original version.

  19. Apport des neutrons à l'analyse structurale des composés partiellement désordonnés

    NASA Astrophysics Data System (ADS)

    Cousson, A.

    2003-02-01

    La cristallographie est un outil extrêmement puissant qui pourrait être utilisé par de nombreux scientifiques dont les sujets de recherche sont en fait très éloignés. L'évolution des techniques ces dernières années a relégué par exemple la cristallographie des rayons X des petites molécules à un rôle mineur, un rôle de service. Certains ont même le sentiment semble-t-il que toutes les connaissances sont contenues dans de multiples logiciels capables par eux-mêmes de conduire une analyse structurale à un résultat correct unique. Il est souhaitable que chacun soit capable de réaliser l'étude structurale du composé qui l'intéresse et bien entendu nécessaire de comprendre ce que l'on fait, la qualité des résultats et leur analyse en dépend. L'objet de cette présentation est de montrer l'apport spécifique de la diffraction de neutrons sur monocristaux à l'étude du désordre, en particulier des atomes d'hydrogène, et ses conséquences sur la compréhension des propriétés physiques, à partir de développements et d'exemples récents.

  20. [Prediction of Promoter Motifs in Virophages].

    PubMed

    Gong, Chaowen; Zhou, Xuewen; Pan, Yingjie; Wang, Yongjie

    2015-07-01

    Virophages have crucial roles in ecosystems and are the transport vectors of genetic materials. To shed light on regulation and control mechanisms in virophage--host systems as well as evolution between virophages and their hosts, the promoter motifs of virophages were predicted on the upstream regions of start codons using an analytical tool for prediction of promoter motifs: Multiple EM for Motif Elicitation. Seventeen potential promoter motifs were identified based on the E-value, location, number and length of promoters in genomes. Sputnik and zamilon motif 2 with AT-rich regions were distributed widely on genomes, suggesting that these motifs may be associated with regulation of the expression of various genes. Motifs containing the TCTA box were predicted to be late promoter motif in mavirus; motifs containing the ATCT box were the potential late promoter motif in the Ace Lake mavirus . AT-rich regions were identified on motif 2 in the Organic Lake virophage, motif 3 in Yellowstone Lake virophage (YSLV)1 and 2, motif 1 in YSLV3, and motif 1 and 2 in YSLV4, respectively. AT-rich regions were distributed widely on the genomes of virophages. All of these motifs may be promoter motifs of virophages. Our results provide insights into further exploration of temporal expression of genes in virophages as well as associations between virophages and giant viruses.

  1. Knowledge discovery of multilevel protein motifs

    SciTech Connect

    Conklin, D.; Glasgow, J.; Fortier, S.

    1994-12-31

    A new category of protein motif is introduced. This type of motif captures, in addition to global structure, the nested structure of its component parts. A dataset of four proteins is represented using this scheme. A structured machine discovery procedure is used to discover recurrent amino acid motifs and this knowledge is utilized for the expression of subsequent protein motif discoveries. Examples of discovered multilevel motifs are presented.

  2. Sequential visibility-graph motifs

    NASA Astrophysics Data System (ADS)

    Iacovacci, Jacopo; Lacasa, Lucas

    2016-04-01

    Visibility algorithms transform time series into graphs and encode dynamical information in their topology, paving the way for graph-theoretical time series analysis as well as building a bridge between nonlinear dynamics and network science. In this work we introduce and study the concept of sequential visibility-graph motifs, smaller substructures of n consecutive nodes that appear with characteristic frequencies. We develop a theory to compute in an exact way the motif profiles associated with general classes of deterministic and stochastic dynamics. We find that this simple property is indeed a highly informative and computationally efficient feature capable of distinguishing among different dynamics and robust against noise contamination. We finally confirm that it can be used in practice to perform unsupervised learning, by extracting motif profiles from experimental heart-rate series and being able, accordingly, to disentangle meditative from other relaxation states. Applications of this general theory include the automatic classification and description of physical, biological, and financial time series.

  3. Neural Circuits: Male Mating Motifs.

    PubMed

    Benton, Richard

    2015-09-02

    Characterizing microcircuit motifs in intact nervous systems is essential to relate neural computations to behavior. In this issue of Neuron, Clowney et al. (2015) identify recurring, parallel feedforward excitatory and inhibitory pathways in male Drosophila's courtship circuitry, which might explain decisive mate choice.

  4. The Thiamin Pyrophosphate-Motif

    NASA Technical Reports Server (NTRS)

    Dominiak, Paulina M.; Ciszak, Ewa M.

    2003-01-01

    Using databases the authors have identified a common thiamin pyrophosphate (TPP)-motif in the family of functionally diverse TPP-dependent enzymes. This common motif consists of multimeric organization of subunits, two catalytic centers, common amino acid sequence, and specific contacts to provide a flip-flop, or alternate site, mechanism of action. Each catalytic center [PP:PYR] is formed at the interface of the PP-domain binding the magnesium ion, pyrophosphate and aminopyrimidine ring of TPP, and the PYR-domain binding the aminopyrimidine ring of that cofactor. A pair of these catalytic centers constitutes the catalytic core [PP:PYR]* within these enzymes. Analysis of the structural elements of this catalytic core reveals novel definition of the common amino acid sequences, which are GX@&(G)@XXGQ, and GDGX25-30 within the PP- domain, and the E&(G)@XXG@ within the PYR-domain, where Q, corresponds to a hydrophobic amino acid. This TPP-motif provides a novel tool for annotation of TPP-dependent enzymes useful in advancing functional proteomics.

  5. The Thiamin Pyrophosphate-Motif

    NASA Technical Reports Server (NTRS)

    Dominiak, P.; Ciszak, E.

    2003-01-01

    Using databases the authors have identified a common thiamin pyrophosphate (TPP)-motif in the family of functionally diverse TPP-dependent enzymes. This common motif consists of multimeric organization of subunits and two catalytic centers. Each catalytic center (PP:PYR) is formed at the interface of the PP-domain binding the magnesium ion, pyrophosphate and amhopyrimidine ring of TPP, and the PYR-domain binding the aminopyrimidine ring of that cofactor. A pair of these catalytic centers constitutes the catalytic core (PP:PYR)(sub 2) within these enzymes. Analysis of the structural elements of this catalytic core reveals novel definition of the common amino acid sequences, which are GXPhiX(sub 4)(G)PhiXXGQ and GDGX(sub 25-30)NN in the PP-domain, and the EX(sub 4)(G)PhiXXGPhi in the PYR-domain, where Phi corresponds to a hydrophobic amino acid. This TPP-motif provides a novel tool for annotation of TPP-dependent enzymes useful in advancing functional proteomics.

  6. Comprehensive discovery of DNA motifs in 349 human cells and tissues reveals new features of motifs.

    PubMed

    Zheng, Yiyu; Li, Xiaoman; Hu, Haiyan

    2015-01-01

    Comprehensive motif discovery under experimental conditions is critical for the global understanding of gene regulation. To generate a nearly complete list of human DNA motifs under given conditions, we employed a novel approach to de novo discover significant co-occurring DNA motifs in 349 human DNase I hypersensitive site datasets. We predicted 845 to 1325 motifs in each dataset, for a total of 2684 non-redundant motifs. These 2684 motifs contained 54.02 to 75.95% of the known motifs in seven large collections including TRANSFAC. In each dataset, we also discovered 43 663 to 2 013 288 motif modules, groups of motifs with their binding sites co-occurring in a significant number of short DNA regions. Compared with known interacting transcription factors in eight resources, the predicted motif modules on average included 84.23% of known interacting motifs. We further showed new features of the predicted motifs, such as motifs enriched in proximal regions rarely overlapped with motifs enriched in distal regions, motifs enriched in 5' distal regions were often enriched in 3' distal regions, etc. Finally, we observed that the 2684 predicted motifs classified the cell or tissue types of the datasets with an accuracy of 81.29%. The resources generated in this study are available at http://server.cs.ucf.edu/predrem/.

  7. A survey of DNA motif finding algorithms

    PubMed Central

    Das, Modan K; Dai, Ho-Kwok

    2007-01-01

    Background Unraveling the mechanisms that regulate gene expression is a major challenge in biology. An important task in this challenge is to identify regulatory elements, especially the binding sites in deoxyribonucleic acid (DNA) for transcription factors. These binding sites are short DNA segments that are called motifs. Recent advances in genome sequence availability and in high-throughput gene expression analysis technologies have allowed for the development of computational methods for motif finding. As a result, a large number of motif finding algorithms have been implemented and applied to various motif models over the past decade. This survey reviews the latest developments in DNA motif finding algorithms. Results Earlier algorithms use promoter sequences of coregulated genes from single genome and search for statistically overrepresented motifs. Recent algorithms are designed to use phylogenetic footprinting or orthologous sequences and also an integrated approach where promoter sequences of coregulated genes and phylogenetic footprinting are used. All the algorithms studied have been reported to correctly detect the motifs that have been previously detected by laboratory experimental approaches, and some algorithms were able to find novel motifs. However, most of these motif finding algorithms have been shown to work successfully in yeast and other lower organisms, but perform significantly worse in higher organisms. Conclusion Despite considerable efforts to date, DNA motif finding remains a complex challenge for biologists and computer scientists. Researchers have taken many different approaches in developing motif discovery tools and the progress made in this area of research is very encouraging. Performance comparison of different motif finding tools and identification of the best tools have proven to be a difficult task because tools are designed based on algorithms and motif models that are diverse and complex and our incomplete understanding of

  8. The Overall Response of Composite Materials Undergoing Large Elastic Deformations

    DTIC Science & Technology

    1990-10-30

    procedure in general to es.et the energy of the composite W (i). For the linear case, it has been shown (MILTON, 1985; AVELLANEDA , 1987) that the DSC...No. 89-0288. 26 P. . CASTAFEDA REFRENcEs AVELLANEDA . M. 1987 Commun. Pure appi. Math. 40, 527. BOUCHER. S. 1974 J. Compos. Mater. 8, 82. BUDIANSKY, B

  9. The Thiamine-Pyrophosphate-Motif

    NASA Technical Reports Server (NTRS)

    Ciszak, Ewa; Dominiak, Paulina

    2004-01-01

    Thiamin pyrophosphate (TPP), a derivative of vitamin B1, is a cofactor for enzymes performing catalysis in pathways of energy production including the well known decarboxylation of a-keto acid dehydrogenases followed by transketolation. TPP-dependent enzymes constitute a structurally and functionally diverse group exhibiting multimeric subunit organization, multiple domains and two chemically equivalent catalytic centers. Annotation of functional TPP-dependcnt enzymes, therefore, has not been trivial due to low sequence similarity related to this complex organization. Our approach to analysis of structures of known TPP-dependent enzymes reveals for the first time features common to this group, which we have termed the TPP-motif. The TPP-motif consists of specific spatial arrangements of structural elements and their specific contacts to provide for a flip-flop, or alternate site, enzymatic mechanism of action. Analysis of structural elements entrained in the flip-flop action displayed by TPP-dependent enzymes reveals a novel definition of the common amino acid sequences. These sequences allow for annotation of TPP-dependent enzymes, thus advancing functional proteomics. Further details of three-dimensional structures of TPP-dependent enzymes will be discussed.

  10. Application de la topologie moléculaire à la prédiction de la viscosité liquide des composés organiques

    NASA Astrophysics Data System (ADS)

    García-Domenech, R.; Villanueva, A.; Gálvez, J.; Gozalbes, R.

    1999-07-01

    Molecular Topology has been applied to search for a mathematical model able to predict liquid viscosity values for an extensive group of organic compounds with C, H, O, N, S and halogenous atoms. The topological descriptors we have used are the connectivity indices from Kier et Hall -up to fourth order-, and the electrotopological indices. Quality of regression equation finally selected has been evaluated by a crossvalidation study. Viscosity of all compounds excepted 1,1,2-trichlorotrifluoro etane is correctly predicted by the model proposed. Nous avons appliqué la topologie moléculaire à la recherche d'un modèle mathématique capable de prédire la viscosité liquide d'un large groupe de composés organiques contenant C, H, O, N, S et des halogènes. Les descripteurs topologiques utilisés pour cette étude des relations quantitatives structure-propiété, R.Q.S.P., sont les indices de connectivité de Kier et Hall -jusqu'à l'ordre quatre- ainsi que les indices atomiques électrotopologiques. La qualité de l'équation de régression multilinéaire obtenue (aussi dite “fonction de connectivité") a été évaluée par une étude de validation croisée. Tous les composés excepté le 1,1,2-trichlorotrifluoréthane s'ajustent au modèle proposé.

  11. MSDmotif: exploring protein sites and motifs

    PubMed Central

    Golovin, Adel; Henrick, Kim

    2008-01-01

    Background Protein structures have conserved features – motifs, which have a sufficient influence on the protein function. These motifs can be found in sequence as well as in 3D space. Understanding of these fragments is essential for 3D structure prediction, modelling and drug-design. The Protein Data Bank (PDB) is the source of this information however present search tools have limited 3D options to integrate protein sequence with its 3D structure. Results We describe here a web application for querying the PDB for ligands, binding sites, small 3D structural and sequence motifs and the underlying database. Novel algorithms for chemical fragments, 3D motifs, ϕ/ψ sequences, super-secondary structure motifs and for small 3D structural motif associations searches are incorporated. The interface provides functionality for visualization, search criteria creation, sequence and 3D multiple alignment options. MSDmotif is an integrated system where a results page is also a search form. A set of motif statistics is available for analysis. This set includes molecule and motif binding statistics, distribution of motif sequences, occurrence of an amino-acid within a motif, correlation of amino-acids side-chain charges within a motif and Ramachandran plots for each residue. The binding statistics are presented in association with properties that include a ligand fragment library. Access is also provided through the distributed Annotation System (DAS) protocol. An additional entry point facilitates XML requests with XML responses. Conclusion MSDmotif is unique by combining chemical, sequence and 3D data in a single search engine with a range of search and visualisation options. It provides multiple views of data found in the PDB archive for exploring protein structures. PMID:18637174

  12. A survey of motif finding Web tools for detecting binding site motifs in ChIP-Seq data.

    PubMed

    Tran, Ngoc Tam L; Huang, Chun-Hsi

    2014-02-20

    ChIP-Seq (chromatin immunoprecipitation sequencing) has provided the advantage for finding motifs as ChIP-Seq experiments narrow down the motif finding to binding site locations. Recent motif finding tools facilitate the motif detection by providing user-friendly Web interface. In this work, we reviewed nine motif finding Web tools that are capable for detecting binding site motifs in ChIP-Seq data. We showed each motif finding Web tool has its own advantages for detecting motifs that other tools may not discover. We recommended the users to use multiple motif finding Web tools that implement different algorithms for obtaining significant motifs, overlapping resemble motifs, and non-overlapping motifs. Finally, we provided our suggestions for future development of motif finding Web tool that better assists researchers for finding motifs in ChIP-Seq data.

  13. Sampling Motif-Constrained Ensembles of Networks

    NASA Astrophysics Data System (ADS)

    Fischer, Rico; Leitão, Jorge C.; Peixoto, Tiago P.; Altmann, Eduardo G.

    2015-10-01

    The statistical significance of network properties is conditioned on null models which satisfy specified properties but that are otherwise random. Exponential random graph models are a principled theoretical framework to generate such constrained ensembles, but which often fail in practice, either due to model inconsistency or due to the impossibility to sample networks from them. These problems affect the important case of networks with prescribed clustering coefficient or number of small connected subgraphs (motifs). In this Letter we use the Wang-Landau method to obtain a multicanonical sampling that overcomes both these problems. We sample, in polynomial time, networks with arbitrary degree sequences from ensembles with imposed motifs counts. Applying this method to social networks, we investigate the relation between transitivity and homophily, and we quantify the correlation between different types of motifs, finding that single motifs can explain up to 60% of the variation of motif profiles.

  14. Temporal motifs in time-dependent networks

    NASA Astrophysics Data System (ADS)

    Kovanen, Lauri; Karsai, Márton; Kaski, Kimmo; Kertész, János; Saramäki, Jari

    2011-11-01

    Temporal networks are commonly used to represent systems where connections between elements are active only for restricted periods of time, such as telecommunication, neural signal processing, biochemical reaction and human social interaction networks. We introduce the framework of temporal motifs to study the mesoscale topological-temporal structure of temporal networks in which the events of nodes do not overlap in time. Temporal motifs are classes of similar event sequences, where the similarity refers not only to topology but also to the temporal order of the events. We provide a mapping from event sequences to coloured directed graphs that enables an efficient algorithm for identifying temporal motifs. We discuss some aspects of temporal motifs, including causality and null models, and present basic statistics of temporal motifs in a large mobile call network.

  15. Efficient motif search in ranked lists and applications to variable gap motifs.

    PubMed

    Leibovich, Limor; Yakhini, Zohar

    2012-07-01

    Sequence elements, at all levels-DNA, RNA and protein, play a central role in mediating molecular recognition and thereby molecular regulation and signaling. Studies that focus on -measuring and investigating sequence-based recognition make use of statistical and computational tools, including approaches to searching sequence motifs. State-of-the-art motif searching tools are limited in their coverage and ability to address large motif spaces. We develop and present statistical and algorithmic approaches that take as input ranked lists of sequences and return significant motifs. The efficiency of our approach, based on suffix trees, allows searches over motif spaces that are not covered by existing tools. This includes searching variable gap motifs-two half sites with a flexible length gap in between-and searching long motifs over large alphabets. We used our approach to analyze several high-throughput measurement data sets and report some validation results as well as novel suggested motifs and motif refinements. We suggest a refinement of the known estrogen receptor 1 motif in humans, where we observe gaps other than three nucleotides that also serve as significant recognition sites, as well as a variable length motif related to potential tyrosine phosphorylation.

  16. [Psychopathological study of lie motif in schizophrenia].

    PubMed

    Otsuka, Koichiro; Kato, Satoshi

    2006-01-01

    The theme of a statement is called "lie motif" by the authors when schizophrenic patients say "I have lied to anybody". We tried to analyse of the psychopathological characteristics and anthropological meanings of the lie motifs in schizophrenia, which has not been thematically examined until now, based on 4 cases, and contrasting with the lie motif (Lügenmotiv) in depression taken up by A. Kraus (1989). We classified the lie motifs in schizophrenia into the following two types: a) the past directive lie motif: the patients speak about their real lie regarding it as a 'petty fault' in their distant past with self-guilty feeling, b) the present directive lie motif: the patients say repeatedly 'I have lied' (about their present speech and behavior), retreating from their previous commitments. The observed false confessions of innocent fault by the patients seem to belong to the present directed lie motif. In comparison with the lie motif in depression, it is characteristic for the lie motif in schizophrenia that the patients feel themselves to already have been caught out by others before they confess the lie. The lie motif in schizophrenia seems to come into being through the attribution process of taking the others' blame on ones' own shoulders, which has been pointed out to be common in the guilt experience in schizophrenia. The others' blame on this occasion is due to "the others' gaze" in the experience of the initial self-centralization (i.e. non delusional self-referential experience) in the early stage of schizophrenia (S. Kato 1999). The others' gaze is supposed to bring about the feeling of amorphous self-revelation which could also be regarded as the guilt feeling without content, to the patients. When the guilt feeling is bound with a past concrete fault, the patients tell the past directive lie motif. On the other hand, when the patients cannot find a past fixed content, and feel their present actions as uncertain and experience them as lies, the

  17. Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction

    NASA Astrophysics Data System (ADS)

    Yeger-Lotem, Esti; Sattath, Shmuel; Kashtan, Nadav; Itzkovitz, Shalev; Milo, Ron; Pinter, Ron Y.; Alon, Uri; Margalit, Hanah

    2004-04-01

    Genes and proteins generate molecular circuitry that enables the cell to process information and respond to stimuli. A major challenge is to identify characteristic patterns in this network of interactions that may shed light on basic cellular mechanisms. Previous studies have analyzed aspects of this network, concentrating on either transcription-regulation or protein-protein interactions. Here we search for composite network motifs: characteristic network patterns consisting of both transcription-regulation and protein-protein interactions that recur significantly more often than in random networks. To this end we developed algorithms for detecting motifs in networks with two or more types of interactions and applied them to an integrated data set of protein-protein interactions and transcription regulation in Saccharomyces cerevisiae. We found a two-protein mixed-feedback loop motif, five types of three-protein motifs exhibiting coregulation and complex formation, and many motifs involving four proteins. Virtually all four-protein motifs consisted of combinations of smaller motifs. This study presents a basic framework for detecting the building blocks of networks with multiple types of interactions.

  18. VARUN: discovering extensible motifs under saturation constraints.

    PubMed

    Apostolico, Alberto; Comin, Matteo; Parida, Laxmi

    2010-01-01

    The discovery of motifs in biosequences is frequently torn between the rigidity of the model on one hand and the abundance of candidates on the other hand. In particular, motifs that include wild cards or "don't cares" escalate exponentially with their number, and this gets only worse if a don't care is allowed to stretch up to some prescribed maximum length. In this paper, a notion of extensible motif in a sequence is introduced and studied, which tightly combines the structure of the motif pattern, as described by its syntactic specification, with the statistical measure of its occurrence count. It is shown that a combination of appropriate saturation conditions and the monotonicity of probabilistic scores over regions of constant frequency afford us significant parsimony in the generation and testing of candidate overrepresented motifs. A suite of software programs called Varun is described, implementing the discovery of extensible motifs of the type considered. The merits of the method are then documented by results obtained in a variety of experiments primarily targeting protein sequence families. Of equal importance seems the fact that the sets of all surprising motifs returned in each experiment are extracted faster and come in much more manageable sizes than would be obtained in the absence of saturation constraints.

  19. Stochastic motif extraction using hidden Markov model

    SciTech Connect

    Fujiwara, Yukiko; Asogawa, Minoru; Konagaya, Akihiko

    1994-12-31

    In this paper, we study the application of an HMM (hidden Markov model) to the problem of representing protein sequences by a stochastic motif. A stochastic protein motif represents the small segments of protein sequences that have a certain function or structure. The stochastic motif, represented by an HMM, has conditional probabilities to deal with the stochastic nature of the motif. This HMM directive reflects the characteristics of the motif, such as a protein periodical structure or grouping. In order to obtain the optimal HMM, we developed the {open_quotes}iterative duplication method{close_quotes} for HMM topology learning. It starts from a small fully-connected network and iterates the network generation and parameter optimization until it achieves sufficient discrimination accuracy. Using this method, we obtained an HMM for a leucine zipper motif. Compared to the accuracy of a symbolic pattern representation with accuracy of 14.8 percent, an HMM achieved 79.3 percent in prediction. Additionally, the method can obtain an HMM for various types of zinc finger motifs, and it might separate the mixed data. We demonstrated that this approach is applicable to the validation of the protein databases; a constructed HMM b as indicated that one protein sequence annotated as {open_quotes}lencine-zipper like sequence{close_quotes} in the database is quite different from other leucine-zipper sequences in terms of likelihood, and we found this discrimination is plausible.

  20. Efficient motif search in ranked lists and applications to variable gap motifs

    PubMed Central

    Leibovich, Limor; Yakhini, Zohar

    2012-01-01

    Sequence elements, at all levels—DNA, RNA and protein, play a central role in mediating molecular recognition and thereby molecular regulation and signaling. Studies that focus on measuring and investigating sequence-based recognition make use of statistical and computational tools, including approaches to searching sequence motifs. State-of-the-art motif searching tools are limited in their coverage and ability to address large motif spaces. We develop and present statistical and algorithmic approaches that take as input ranked lists of sequences and return significant motifs. The efficiency of our approach, based on suffix trees, allows searches over motif spaces that are not covered by existing tools. This includes searching variable gap motifs—two half sites with a flexible length gap in between—and searching long motifs over large alphabets. We used our approach to analyze several high-throughput measurement data sets and report some validation results as well as novel suggested motifs and motif refinements. We suggest a refinement of the known estrogen receptor 1 motif in humans, where we observe gaps other than three nucleotides that also serve as significant recognition sites, as well as a variable length motif related to potential tyrosine phosphorylation. PMID:22416066

  1. RSAT peak-motifs: motif analysis in full-size ChIP-seq datasets.

    PubMed

    Thomas-Chollier, Morgane; Herrmann, Carl; Defrance, Matthieu; Sand, Olivier; Thieffry, Denis; van Helden, Jacques

    2012-02-01

    ChIP-seq is increasingly used to characterize transcription factor binding and chromatin marks at a genomic scale. Various tools are now available to extract binding motifs from peak data sets. However, most approaches are only available as command-line programs, or via a website but with size restrictions. We present peak-motifs, a computational pipeline that discovers motifs in peak sequences, compares them with databases, exports putative binding sites for visualization in the UCSC genome browser and generates an extensive report suited for both naive and expert users. It relies on time- and memory-efficient algorithms enabling the treatment of several thousand peaks within minutes. Regarding time efficiency, peak-motifs outperforms all comparable tools by several orders of magnitude. We demonstrate its accuracy by analyzing data sets ranging from 4000 to 1,28,000 peaks for 12 embryonic stem cell-specific transcription factors. In all cases, the program finds the expected motifs and returns additional motifs potentially bound by cofactors. We further apply peak-motifs to discover tissue-specific motifs in peak collections for the p300 transcriptional co-activator. To our knowledge, peak-motifs is the only tool that performs a complete motif analysis and offers a user-friendly web interface without any restriction on sequence size or number of peaks.

  2. Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas.

    PubMed

    Petrov, Anton I; Zirbel, Craig L; Leontis, Neocles B

    2013-10-01

    The analysis of atomic-resolution RNA three-dimensional (3D) structures reveals that many internal and hairpin loops are modular, recurrent, and structured by conserved non-Watson-Crick base pairs. Structurally similar loops define RNA 3D motifs that are conserved in homologous RNA molecules, but can also occur at nonhomologous sites in diverse RNAs, and which often vary in sequence. To further our understanding of RNA motif structure and sequence variability and to provide a useful resource for structure modeling and prediction, we present a new method for automated classification of internal and hairpin loop RNA 3D motifs and a new online database called the RNA 3D Motif Atlas. To classify the motif instances, a representative set of internal and hairpin loops is automatically extracted from a nonredundant list of RNA-containing PDB files. Their structures are compared geometrically, all-against-all, using the FR3D program suite. The loops are clustered into motif groups, taking into account geometric similarity and structural annotations and making allowance for a variable number of bulged bases. The automated procedure that we have implemented identifies all hairpin and internal loop motifs previously described in the literature. All motif instances and motif groups are assigned unique and stable identifiers and are made available in the RNA 3D Motif Atlas (http://rna.bgsu.edu/motifs), which is automatically updated every four weeks. The RNA 3D Motif Atlas provides an interactive user interface for exploring motif diversity and tools for programmatic data access.

  3. Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas

    PubMed Central

    Petrov, Anton I.; Zirbel, Craig L.; Leontis, Neocles B.

    2013-01-01

    The analysis of atomic-resolution RNA three-dimensional (3D) structures reveals that many internal and hairpin loops are modular, recurrent, and structured by conserved non-Watson–Crick base pairs. Structurally similar loops define RNA 3D motifs that are conserved in homologous RNA molecules, but can also occur at nonhomologous sites in diverse RNAs, and which often vary in sequence. To further our understanding of RNA motif structure and sequence variability and to provide a useful resource for structure modeling and prediction, we present a new method for automated classification of internal and hairpin loop RNA 3D motifs and a new online database called the RNA 3D Motif Atlas. To classify the motif instances, a representative set of internal and hairpin loops is automatically extracted from a nonredundant list of RNA-containing PDB files. Their structures are compared geometrically, all-against-all, using the FR3D program suite. The loops are clustered into motif groups, taking into account geometric similarity and structural annotations and making allowance for a variable number of bulged bases. The automated procedure that we have implemented identifies all hairpin and internal loop motifs previously described in the literature. All motif instances and motif groups are assigned unique and stable identifiers and are made available in the RNA 3D Motif Atlas (http://rna.bgsu.edu/motifs), which is automatically updated every four weeks. The RNA 3D Motif Atlas provides an interactive user interface for exploring motif diversity and tools for programmatic data access. PMID:23970545

  4. [Scanning electronmicroscopic study of 3 composite filling materials after 1 year's use].

    PubMed

    Triadan, H

    1976-05-01

    This is an in-vivo comparative test of two test materials, composites Compo-Cap and Cosmic against Adaptic on a monkey (Macaca speciosa) over one year. No significant differences could be found and the defects on margins and in the surface was similar. Undubitable secondary caries could--unlike in a previous test with Epoxylite--not be found with these fillings.

  5. Short sequence motifs, overrepresented in mammalian conservednon-coding sequences

    SciTech Connect

    Minovitsky, Simon; Stegmaier, Philip; Kel, Alexander; Kondrashov,Alexey S.; Dubchak, Inna

    2007-02-21

    Background: A substantial fraction of non-coding DNAsequences of multicellular eukaryotes is under selective constraint. Inparticular, ~;5 percent of the human genome consists of conservednon-coding sequences (CNSs). CNSs differ from other genomic sequences intheir nucleotide composition and must play important functional roles,which mostly remain obscure.Results: We investigated relative abundancesof short sequence motifs in all human CNSs present in the human/mousewhole-genome alignments vs. three background sets of sequences: (i)weakly conserved or unconserved non-coding sequences (non-CNSs); (ii)near-promoter sequences (located between nucleotides -500 and -1500,relative to a start of transcription); and (iii) random sequences withthe same nucleotide composition as that of CNSs. When compared tonon-CNSs and near-promoter sequences, CNSs possess an excess of AT-richmotifs, often containing runs of identical nucleotides. In contrast, whencompared to random sequences, CNSs contain an excess of GC-rich motifswhich, however, lack CpG dinucleotides. Thus, abundance of short sequencemotifs in human CNSs, taken as a whole, is mostly determined by theiroverall compositional properties and not by overrepresentation of anyspecific short motifs. These properties are: (i) high AT-content of CNSs,(ii) a tendency, probably due to context-dependent mutation, of A's andT's to clump, (iii) presence of short GC-rich regions, and (iv) avoidanceof CpG contexts, due to their hypermutability. Only a small number ofshort motifs, overrepresented in all human CNSs are similar to bindingsites of transcription factors from the FOX family.Conclusion: Human CNSsas a whole appear to be too broad a class of sequences to possess strongfootprints of any short sequence-specific functions. Such footprintsshould be studied at the level of functional subclasses of CNSs, such asthose which flank genes with a particular pattern of expression. Overallproperties of CNSs are affected by patterns in

  6. Network motif identification in stochastic networks

    NASA Astrophysics Data System (ADS)

    Jiang, Rui; Tu, Zhidong; Chen, Ting; Sun, Fengzhu

    2006-06-01

    Network motifs have been identified in a wide range of networks across many scientific disciplines and are suggested to be the basic building blocks of most complex networks. Nonetheless, many networks come with intrinsic and/or experimental uncertainties and should be treated as stochastic networks. The building blocks in these networks thus may also have stochastic properties. In this article, we study stochastic network motifs derived from families of mutually similar but not necessarily identical patterns of interconnections. We establish a finite mixture model for stochastic networks and develop an expectation-maximization algorithm for identifying stochastic network motifs. We apply this approach to the transcriptional regulatory networks of Escherichia coli and Saccharomyces cerevisiae, as well as the protein-protein interaction networks of seven species, and identify several stochastic network motifs that are consistent with current biological knowledge. expectation-maximization algorithm | mixture model | transcriptional regulatory network | protein-protein interaction network

  7. iMotifs: an integrated sequence motif visualization and analysis environment

    PubMed Central

    Piipari, Matias; Down, Thomas A.; Saini, Harpreet; Enright, Anton; Hubbard, Tim J.P.

    2010-01-01

    Motivation: Short sequence motifs are an important class of models in molecular biology, used most commonly for describing transcription factor binding site specificity patterns. High-throughput methods have been recently developed for detecting regulatory factor binding sites in vivo and in vitro and consequently high-quality binding site motif data are becoming available for increasing number of organisms and regulatory factors. Development of intuitive tools for the study of sequence motifs is therefore important. iMotifs is a graphical motif analysis environment that allows visualization of annotated sequence motifs and scored motif hits in sequences. It also offers motif inference with the sensitive NestedMICA algorithm, as well as overrepresentation and pairwise motif matching capabilities. All of the analysis functionality is provided without the need to convert between file formats or learn different command line interfaces. The application includes a bundled and graphically integrated version of the NestedMICA motif inference suite that has no outside dependencies. Problems associated with local deployment of software are therefore avoided. Availability: iMotifs is licensed with the GNU Lesser General Public License v2.0 (LGPL 2.0). The software and its source is available at http://wiki.github.com/mz2/imotifs and can be run on Mac OS X Leopard (Intel/PowerPC). We also provide a cross-platform (Linux, OS X, Windows) LGPL 2.0 licensed library libxms for the Perl, Ruby, R and Objective-C programming languages for input and output of XMS formatted annotated sequence motif set files. Contact: matias.piipari@gmail.com; imotifs@googlegroups.com PMID:20106815

  8. Characteristic motifs for families of allergenic proteins

    PubMed Central

    Ivanciuc, Ovidiu; Garcia, Tzintzuni; Torres, Miguel; Schein, Catherine H.; Braun, Werner

    2008-01-01

    The identification of potential allergenic proteins is usually done by scanning a database of allergenic proteins and locating known allergens with a high sequence similarity. However, there is no universally accepted cut-off value for sequence similarity to indicate potential IgE cross-reactivity. Further, overall sequence similarity may be less important than discrete areas of similarity in proteins with homologous structure. To identify such areas, we first classified all allergens and their subdomains in the Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/) to their closest protein families as defined in Pfam, and identified conserved physicochemical property motifs characteristic of each group of sequences. Allergens populate only a small subset of all known Pfam families, as all allergenic proteins in SDAP could be grouped to only 130 (of 9318 total) Pfams, and 31 families contain more than four allergens. Conserved physicochemical property motifs for the aligned sequences of the most populated Pfam families were identified with the PCPMer program suite and catalogued in the webserver Motif-Mate (http://born.utmb.edu/motifmate/summary.php). We also determined specific motifs for allergenic members of a family that could distinguish them from non-allergenic ones. These allergen specific motifs should be most useful in database searches for potential allergens. We found that sequence motifs unique to the allergens in three families (seed storage proteins, Bet v 1, and tropomyosin) overlap with known IgE epitopes, thus providing evidence that our motif based approach can be used to assess the potential allergenicity of novel proteins. PMID:18951633

  9. Modeling gene regulatory network motifs using statecharts

    PubMed Central

    2012-01-01

    Background Gene regulatory networks are widely used by biologists to describe the interactions among genes, proteins and other components at the intra-cellular level. Recently, a great effort has been devoted to give gene regulatory networks a formal semantics based on existing computational frameworks. For this purpose, we consider Statecharts, which are a modular, hierarchical and executable formal model widely used to represent software systems. We use Statecharts for modeling small and recurring patterns of interactions in gene regulatory networks, called motifs. Results We present an improved method for modeling gene regulatory network motifs using Statecharts and we describe the successful modeling of several motifs, including those which could not be modeled or whose models could not be distinguished using the method of a previous proposal. We model motifs in an easy and intuitive way by taking advantage of the visual features of Statecharts. Our modeling approach is able to simulate some interesting temporal properties of gene regulatory network motifs: the delay in the activation and the deactivation of the "output" gene in the coherent type-1 feedforward loop, the pulse in the incoherent type-1 feedforward loop, the bistability nature of double positive and double negative feedback loops, the oscillatory behavior of the negative feedback loop, and the "lock-in" effect of positive autoregulation. Conclusions We present a Statecharts-based approach for the modeling of gene regulatory network motifs in biological systems. The basic motifs used to build more complex networks (that is, simple regulation, reciprocal regulation, feedback loop, feedforward loop, and autoregulation) can be faithfully described and their temporal dynamics can be analyzed. PMID:22536967

  10. Identifying combinatorial regulation of transcription factors and binding motifs

    PubMed Central

    Kato, Mamoru; Hata, Naoya; Banerjee, Nilanjana; Futcher, Bruce; Zhang, Michael Q

    2004-01-01

    Background Combinatorial interaction of transcription factors (TFs) is important for gene regulation. Although various genomic datasets are relevant to this issue, each dataset provides relatively weak evidence on its own. Developing methods that can integrate different sequence, expression and localization data have become important. Results Here we use a novel method that integrates chromatin immunoprecipitation (ChIP) data with microarray expression data and with combinatorial TF-motif analysis. We systematically identify combinations of transcription factors and of motifs. The various combinations of TFs involved multiple binding mechanisms. We reconstruct a new combinatorial regulatory map of the yeast cell cycle in which cell-cycle regulation can be drawn as a chain of extended TF modules. We find that the pairwise combination of a TF for an early cell-cycle phase and a TF for a later phase is often used to control gene expression at intermediate times. Thus the number of distinct times of gene expression is greater than the number of transcription factors. We also see that some TF modules control branch points (cell-cycle entry and exit), and in the presence of appropriate signals they can allow progress along alternative pathways. Conclusions Combining different data sources can increase statistical power as demonstrated by detecting TF interactions and composite TF-binding motifs. The original picture of a chain of simple cell-cycle regulators can be extended to a chain of composite regulatory modules: different modules may share a common TF component in the same pathway or a TF component cross-talking to other pathways. PMID:15287978

  11. The Verrucomicrobia LexA-Binding Motif: Insights into the Evolutionary Dynamics of the SOS Response

    PubMed Central

    Erill, Ivan; Campoy, Susana; Kılıç, Sefa; Barbé, Jordi

    2016-01-01

    The SOS response is the primary bacterial mechanism to address DNA damage, coordinating multiple cellular processes that include DNA repair, cell division, and translesion synthesis. In contrast to other regulatory systems, the composition of the SOS genetic network and the binding motif of its transcriptional repressor, LexA, have been shown to vary greatly across bacterial clades, making it an ideal system to study the co-evolution of transcription factors and their regulons. Leveraging comparative genomics approaches and prior knowledge on the core SOS regulon, here we define the binding motif of the Verrucomicrobia, a recently described phylum of emerging interest due to its association with eukaryotic hosts. Site directed mutagenesis of the Verrucomicrobium spinosum recA promoter confirms that LexA binds a 14 bp palindromic motif with consensus sequence TGTTC-N4-GAACA. Computational analyses suggest that recognition of this novel motif is determined primarily by changes in base-contacting residues of the third alpha helix of the LexA helix-turn-helix DNA binding motif. In conjunction with comparative genomics analysis of the LexA regulon in the Verrucomicrobia phylum, electrophoretic shift assays reveal that LexA binds to operators in the promoter region of DNA repair genes and a mutagenesis cassette in this organism, and identify previously unreported components of the SOS response. The identification of tandem LexA-binding sites generating instances of other LexA-binding motifs in the lexA gene promoter of Verrucomicrobia species leads us to postulate a novel mechanism for LexA-binding motif evolution. This model, based on gene duplication, successfully addresses outstanding questions in the intricate co-evolution of the LexA protein, its binding motif and the regulatory network it controls. PMID:27489856

  12. A comparison between corn and grain sorghum fermentation rates, distillers dried grains with solubles composition, and lipid profiles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Interest in utilization of feedstocks other than corn for fuel ethanol production has been increasing due to political as well as environmental reasons. Grain sorghum is an identified alternative that has a number of potential benefits relative to corn in both composition and agronomic traits. Compo...

  13. Motif-based embedding for graph clustering

    NASA Astrophysics Data System (ADS)

    Lim, Sungsu; Lee, Jae-Gil

    2016-12-01

    Community detection in complex networks is a fundamental problem that has been extensively studied owing to its wide range of applications. However, because community detection methods typically rely on the relations between vertices in networks, they may fail to discover higher-order graph substructures, called the network motifs. In this paper, we propose a novel embedding method for graph clustering that considers higher-order relationships involving multiple vertices. We show that our embedding method, which we call motif-based embedding, is more effective in detecting communities than existing graph embedding methods, spectral embedding and force-directed embedding, both theoretically and experimentally.

  14. Calendar motifs on Getashen hydria

    NASA Astrophysics Data System (ADS)

    Vrtanesyan, Garegin

    2015-07-01

    Getashen hydria was found in the tombs of the middle bronze age (the first third of the second Millennium B.C.) in Armenia (Lake Sevan). It shows a scene consisting of three friezes. On the lower frieze depicts six zoomorphic figures, on an average six frieze waterfowl, and on top, is the graphic signs. Calendar motives of this composition have a numeric expression, six zoomorphic figures on the lower and middle friezes. Division of the annual cycle into two parts is known in the calendars of the ancient Indo-Iranian ("great summer" and "the great winter"). Animals on the lower frieze of the second mark, "winter" road of the Sun, because in this period are the most important events, ensuring the reproduction of the economy of the society. This rut ungulates - wild (deer) and domestic (goats). Moreover, the gon goats end in December, almost coinciding with the onset of the winter solstice. A couple of dogs on the lower frieze marks the version of the myth, imprisoned in the rock hero - the Sun (Mihr - Artavazd), to which his dogs have to chew the chains, anticipating his exit at the winter solstice. This is indicated by the direction of their movement, the Sun moves from left to right for an observer, only when located on the South side of the sky (i.e., beginning with the autumnal equinox). The most important event of the period of "summer road" of the Sun is the vernal equinox, which coincide with the arrival of waterfowl (ducks, geese). Their direction on the second frieze (left to right) corresponds to the position of the observer, facing North.

  15. Inhibition de la corrosion d'acier au carbone en milieu H3PO4 2M par des composés organiques de type ``triazine''

    NASA Astrophysics Data System (ADS)

    Bekkouch, K.; Aouniti, A.; Hammouti, B.; Kertit, S.

    1999-05-01

    The effect of addition of some triazine compounds on the corrosion behaviour of steel in 2M H3PO4 has been studied by weight loss and electrochemical polarisation methods. Both methods showed that the dissolution rate was dependent on the chemical properties and concentration of the product. From comparison of results, it was found that 6-azathymine (T6) is the best inhibitor and its inhibition efficiency reaches a maximum value of 86% at 10-3 M. Polarisation measurements indicated that T6 acts as cathodic inhibitor by merely blocking the reaction sites without changing the mechanism of the hydrogen evolution reaction. It was found that T6 was adsorbed on steel surface according to a Langmuir isotherm model. The effect of temperature indicated that inhibition efficiency of T6 is dependent on the temperature in the range 25-50 circC. L'effet de l'addition de certains composés organiques de type triazine sur la corrosion d'un acier en milieu H3PO4 2M a été étudié à l'aide des méthodes électrochimiques et gravimétriques. Les résultats obtenus ont montré que la vitesse de dissolution de l'acier dépend de la structure moléculaire et de la concentration du produit. La comparaison des efficacités inhibitrices montre que le 6-azathymine (T6) est le meilleur inhibiteur de la série des triazines testés. L'efficacité inhibitrice du T6 atteint une valeur maximale de 86 % à 10-3 M. L'allure des courbes de polarisation indique que le T6 agit essentiellement comme inhibiteur de type cathodique par adsorption à la surface de l'acier selon le modèle de l'isotherme de Langmuir. L'efficacité inhibitrice du T6 dépend de la température dans le domaine allant de 25 à 50 circC.

  16. Genomic analysis of membrane protein families: abundance and conserved motifs

    PubMed Central

    Liu, Yang; Engelman, Donald M; Gerstein, Mark

    2002-01-01

    Background Polytopic membrane proteins can be related to each other on the basis of the number of transmembrane helices and sequence similarities. Building on the Pfam classification of protein domain families, and using transmembrane-helix prediction and sequence-similarity searching, we identified a total of 526 well-characterized membrane protein families in 26 recently sequenced genomes. To this we added a clustering of a number of predicted but unclassified membrane proteins, resulting in a total of 637 membrane protein families. Results Analysis of the occurrence and composition of these families revealed several interesting trends. The number of assigned membrane protein domains has an approximately linear relationship to the total number of open reading frames (ORFs) in 26 genomes studied. Caenorhabditis elegans is an apparent outlier, because of its high representation of seven-span transmembrane (7-TM) chemoreceptor families. In all genomes, including that of C. elegans, the number of distinct membrane protein families has a logarithmic relation to the number of ORFs. Glycine, proline, and tyrosine locations tend to be conserved in transmembrane regions within families, whereas isoleucine, valine, and methionine locations are relatively mutable. Analysis of motifs in putative transmembrane helices reveals that GxxxG and GxxxxxxG (which can be written GG4 and GG7, respectively; see Materials and methods) are among the most prevalent. This was noted in earlier studies; we now find these motifs are particularly well conserved in families, however, especially those corresponding to transporters, symporters, and channels. Conclusions We carried out a genome-wide analysis on patterns of the classified polytopic membrane protein families and analyzed the distribution of conserved amino acids and motifs in the transmembrane helix regions in these families. PMID:12372142

  17. Network motifs modulate druggability of cellular targets

    PubMed Central

    Wu, Fan; Ma, Cong; Tan, Cheemeng

    2016-01-01

    Druggability refers to the capacity of a cellular target to be modulated by a small-molecule drug. To date, druggability is mainly studied by focusing on direct binding interactions between a drug and its target. However, druggability is impacted by cellular networks connected to a drug target. Here, we use computational approaches to reveal basic principles of network motifs that modulate druggability. Through quantitative analysis, we find that inhibiting self-positive feedback loop is a more robust and effective treatment strategy than inhibiting other regulations, and adding direct regulations to a drug-target generally reduces its druggability. The findings are explained through analytical solution of the motifs. Furthermore, we find that a consensus topology of highly druggable motifs consists of a negative feedback loop without any positive feedback loops, and consensus motifs with low druggability have multiple positive direct regulations and positive feedback loops. Based on the discovered principles, we predict potential genetic targets in Escherichia coli that have either high or low druggability based on their network context. Our work establishes the foundation toward identifying and predicting druggable targets based on their network topology. PMID:27824147

  18. Motifs and structural blocks retrieval by GHT

    NASA Astrophysics Data System (ADS)

    Cantoni, Virginio; Ferone, Alessio; Petrosino, Alfredo; Polat, Ozlem

    2014-06-01

    The structure of a protein gives more insight on the protein function than its amino acid sequence. Protein structure analysis and comparison are important for understanding the evolutionary relationships among proteins, predicting protein functions, and predicting protein folding. Proteins are formed by two basic regular 3D structural patterns, called Secondary Structures (SSs): helices and sheets. A structural motif is a compact 3D protein block referring to a small specific combination of secondary structural elements, which appears in a variety of molecules. In this paper we compare a few approaches for motif retrieval based on the Generalized Hough Transform (GHT). A primary technique is to adopt the single SS as structural primitives; alternatives are to adopt a SSs pair as primitive structural element, or a SSs triplet, and so on up-to an entire motif. The richer the primitive, the higher the time for pre-analysis and search, and the simpler the inspection process on the parameter space for analyzing the peaks. Performance comparisons, in terms of precision and computation time, are here presented considering the retrieval of motifs composed by three to five SSs for more than 15 million searches. The approach can be easily applied to the retrieval of greater blocks, up to protein domains, or even entire proteins.

  19. Inorganic Composite Materials in Japan: Status and Trends

    DTIC Science & Technology

    1989-11-01

    Figure 7. Static specific strength versus specific modulus of aluminum and titanium base metal matrix composites (MMC) at room temperature. Redrawn...is planned with have already done some preliminary work) more sayby engineers and scientists and less on titanium and aluminide matrix compos- by... Young B. Kim and Seikob Sakivamna. Office of Naval Research. Tokyo. Deceumber 1983 Lirly monographs, which were authored in various elements of the ONR

  20. A survey of motif finding Web tools for detecting binding site motifs in ChIP-Seq data

    PubMed Central

    2014-01-01

    Abstract ChIP-Seq (chromatin immunoprecipitation sequencing) has provided the advantage for finding motifs as ChIP-Seq experiments narrow down the motif finding to binding site locations. Recent motif finding tools facilitate the motif detection by providing user-friendly Web interface. In this work, we reviewed nine motif finding Web tools that are capable for detecting binding site motifs in ChIP-Seq data. We showed each motif finding Web tool has its own advantages for detecting motifs that other tools may not discover. We recommended the users to use multiple motif finding Web tools that implement different algorithms for obtaining significant motifs, overlapping resemble motifs, and non-overlapping motifs. Finally, we provided our suggestions for future development of motif finding Web tool that better assists researchers for finding motifs in ChIP-Seq data. Reviewers This article was reviewed by Prof. Sandor Pongor, Dr. Yuriy Gusev, and Dr. Shyam Prabhakar (nominated by Prof. Limsoon Wong). PMID:24555784

  1. CombiMotif: A new algorithm for network motifs discovery in protein-protein interaction networks

    NASA Astrophysics Data System (ADS)

    Luo, Jiawei; Li, Guanghui; Song, Dan; Liang, Cheng

    2014-12-01

    Discovering motifs in protein-protein interaction networks is becoming a current major challenge in computational biology, since the distribution of the number of network motifs can reveal significant systemic differences among species. However, this task can be computationally expensive because of the involvement of graph isomorphic detection. In this paper, we present a new algorithm (CombiMotif) that incorporates combinatorial techniques to count non-induced occurrences of subgraph topologies in the form of trees. The efficiency of our algorithm is demonstrated by comparing the obtained results with the current state-of-the art subgraph counting algorithms. We also show major differences between unicellular and multicellular organisms. The datasets and source code of CombiMotif are freely available upon request.

  2. Overlapping ETS and CRE Motifs ((G/C)CGGAAGTGACGTCA) preferentially bound by GABPα and CREB proteins.

    PubMed

    Chatterjee, Raghunath; Zhao, Jianfei; He, Ximiao; Shlyakhtenko, Andrey; Mann, Ishminder; Waterfall, Joshua J; Meltzer, Paul; Sathyanarayana, B K; FitzGerald, Peter C; Vinson, Charles

    2012-10-01

    Previously, we identified 8-bps long DNA sequences (8-mers) that localize in human proximal promoters and grouped them into known transcription factor binding sites (TFBS). We now examine split 8-mers consisting of two 4-mers separated by 1-bp to 30-bps (X(4)-N(1-30)-X(4)) to identify pairs of TFBS that localize in proximal promoters at a precise distance. These include two overlapping TFBS: the ETS⇔ETS motif ((C/G)CCGGAAGCGGAA) and the ETS⇔CRE motif ((C/G)CGGAAGTGACGTCAC). The nucleotides in bold are part of both TFBS. Molecular modeling shows that the ETS⇔CRE motif can be bound simultaneously by both the ETS and the B-ZIP domains without protein-protein clashes. The electrophoretic mobility shift assay (EMSA) shows that the ETS protein GABPα and the B-ZIP protein CREB preferentially bind to the ETS⇔CRE motif only when the two TFBS overlap precisely. In contrast, the ETS domain of ETV5 and CREB interfere with each other for binding the ETS⇔CRE. The 11-mer (CGGAAGTGACG), the conserved part of the ETS⇔CRE motif, occurs 226 times in the human genome and 83% are in known regulatory regions. In vivo GABPα and CREB ChIP-seq peaks identified the ETS⇔CRE as the most enriched motif occurring in promoters of genes involved in mRNA processing, cellular catabolic processes, and stress response, suggesting that a specific class of genes is regulated by this composite motif.

  3. Pressure-dependent formation of i-motif and G-quadruplex DNA structures.

    PubMed

    Takahashi, S; Sugimoto, N

    2015-12-14

    Pressure is an important physical stimulus that can influence the fate of cells by causing structural changes in biomolecules such as DNA. We investigated the effect of high pressure on the folding of duplex, DNA i-motif, and G-quadruplex (G4) structures; the non-canonical structures may be modulators of expression of genes involved in cancer progression. The i-motif structure was stabilized by high pressure, whereas the G4 structure was destabilized. The melting temperature of an intramolecular i-motif formed by 5'-dCGG(CCT)10CGG-3' increased from 38.8 °C at atmospheric pressure to 61.5 °C at 400 MPa. This effect was also observed in the presence of 40 wt% ethylene glycol, a crowding agent. In the presence of 40 wt% ethylene glycol, the G4 structure was less destabilized than in the absence of the crowding agent. P-T stability diagrams of duplex DNA with a telomeric sequence indicated that the duplex is more stable than G4 and i-motif structures under low pressure, but the i-motif dominates the structural composition under high pressure. Under crowding conditions, the P-T diagrams indicated that the duplex does not form under high pressure, and i-motif and G4 structures dominate. Our findings imply that temperature regulates the formation of the duplex structure, whereas pressure triggers the formation of non-canonical DNA structures like i-motif and G4. These results suggest that pressure impacts the function of nucleic acids by stabilizing non-canonical structures; this may be relevant to deep sea organisms and during evolution under prebiotic conditions.

  4. Discovery and validation of information theory-based transcription factor and cofactor binding site motifs.

    PubMed

    Lu, Ruipeng; Mucaki, Eliseos J; Rogan, Peter K

    2016-11-28

    Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs. We obtained contiguous and bipartite information theory-based position weight matrices (iPWMs) for 93 sequence-specific TFs, discovered 23 cofactor motifs for 127 TFs and revealed six high-confidence novel motifs. The reliability and accuracy of these iPWMs were determined via four independent validation methods, including the detection of experimentally proven binding sites, explanation of effects of characterized SNPs, comparison with previously published motifs and statistical analyses. We also predict previously unreported TF coregulatory interactions (e.g. TF complexes). These iPWMs constitute a powerful tool for predicting the effects of sequence variants in known binding sites, performing mutation analysis on regulatory SNPs and predicting previously unrecognized binding sites and target genes.

  5. A Review of Functional Motifs Utilized by Viruses

    PubMed Central

    Sobhy, Haitham

    2016-01-01

    Short linear motifs (SLiM) are short peptides that facilitate protein function and protein-protein interactions. Viruses utilize these motifs to enter into the host, interact with cellular proteins, or egress from host cells. Studying functional motifs may help to predict protein characteristics, interactions, or the putative cellular role of a protein. In virology, it may reveal aspects of the virus tropism and help find antiviral therapeutics. This review highlights the recent understanding of functional motifs utilized by viruses. Special attention was paid to the function of proteins harboring these motifs, and viruses encoding these proteins. The review highlights motifs involved in (i) immune response and post-translational modifications (e.g., ubiquitylation, SUMOylation or ISGylation); (ii) virus-host cell interactions, including virus attachment, entry, fusion, egress and nuclear trafficking; (iii) virulence and antiviral activities; (iv) virion structure; and (v) low-complexity regions (LCRs) or motifs enriched with residues (Xaa-rich motifs). PMID:28248213

  6. Functional Motifs in Biochemical Reaction Networks

    PubMed Central

    Tyson, John J.; Novák, Béla

    2013-01-01

    The signal-response characteristics of a living cell are determined by complex networks of interacting genes, proteins, and metabolites. Understanding how cells respond to specific challenges, how these responses are contravened in diseased cells, and how to intervene pharmacologically in the decision-making processes of cells requires an accurate theory of the information-processing capabilities of macromolecular regulatory networks. Adopting an engineer’s approach to control systems, we ask whether realistic cellular control networks can be decomposed into simple regulatory motifs that carry out specific functions in a cell. We show that such functional motifs exist and review the experimental evidence that they control cellular responses as expected. PMID:20055671

  7. On the Kernelization Complexity of Colorful Motifs

    NASA Astrophysics Data System (ADS)

    Ambalath, Abhimanyu M.; Balasundaram, Radheshyam; Rao H., Chintan; Koppula, Venkata; Misra, Neeldhara; Philip, Geevarghese; Ramanujan, M. S.

    The Colorful Motif problem asks if, given a vertex-colored graph G, there exists a subset S of vertices of G such that the graph induced by G on S is connected and contains every color in the graph exactly once. The problem is motivated by applications in computational biology and is also well-studied from the theoretical point of view. In particular, it is known to be NP-complete even on trees of maximum degree three [Fellows et al, ICALP 2007]. In their pioneering paper that introduced the color-coding technique, Alon et al. [STOC 1995] show, inter alia, that the problem is FPT on general graphs. More recently, Cygan et al. [WG 2010] showed that Colorful Motif is NP-complete on comb graphs, a special subclass of the set of trees of maximum degree three. They also showed that the problem is not likely to admit polynomial kernels on forests.

  8. Sequential motif profile of natural visibility graphs

    NASA Astrophysics Data System (ADS)

    Iacovacci, Jacopo; Lacasa, Lucas

    2016-11-01

    The concept of sequential visibility graph motifs—subgraphs appearing with characteristic frequencies in the visibility graphs associated to time series—has been advanced recently along with a theoretical framework to compute analytically the motif profiles associated to horizontal visibility graphs (HVGs). Here we develop a theory to compute the profile of sequential visibility graph motifs in the context of natural visibility graphs (VGs). This theory gives exact results for deterministic aperiodic processes with a smooth invariant density or stochastic processes that fulfill the Markov property and have a continuous marginal distribution. The framework also allows for a linear time numerical estimation in the case of empirical time series. A comparison between the HVG and the VG case (including evaluation of their robustness for short series polluted with measurement noise) is also presented.

  9. Chiral Alkyl Halides: Underexplored Motifs in Medicine

    PubMed Central

    Gál, Bálint; Bucher, Cyril; Burns, Noah Z.

    2016-01-01

    While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and medicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biological systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the role that chiral alkyl halides can play in drug discovery. Through a series of case studies, we demonstrate in this review that these motifs can indeed be stable under physiological conditions, and that halogenation can enhance bioactivity through both steric and electronic effects. Our hope is that, by placing such compounds in the minds of the chemical community, they may gain more traction in drug discovery and inspire more synthetic chemists to develop methods for selective halogenation. PMID:27827902

  10. Anticipated synchronization in neuronal network motifs

    NASA Astrophysics Data System (ADS)

    Matias, F. S.; Gollo, L. L.; Carelli, P. V.; Copelli, M.; Mirasso, C. R.

    2013-01-01

    Two identical dynamical systems coupled unidirectionally (in a so called master-slave configuration) exhibit anticipated synchronization (AS) if the one which receives the coupling (the slave) also receives a negative delayed self-feedback. In oscillatory neuronal systems AS is characterized by a phase-locking with negative time delay τ between the spikes of the master and of the slave (slave fires before the master), while in the usual delayed synchronization (DS) regime τ is positive (slave fires after the master). A 3-neuron motif in which the slave self-feedback is replaced by a feedback loop mediated by an interneuron can exhibits both AS and DS regimes. Here we show that AS is robust in the presence of noise in a 3 Hodgkin-Huxley type neuronal motif. We also show that AS is stable for large values of τ in a chain of connected slaves-interneurons.

  11. Analyzing network reliability using structural motifs.

    PubMed

    Khorramzadeh, Yasamin; Youssef, Mina; Eubank, Stephen; Mowlaei, Shahir

    2015-04-01

    This paper uses the reliability polynomial, introduced by Moore and Shannon in 1956, to analyze the effect of network structure on diffusive dynamics such as the spread of infectious disease. We exhibit a representation for the reliability polynomial in terms of what we call structural motifs that is well suited for reasoning about the effect of a network's structural properties on diffusion across the network. We illustrate by deriving several general results relating graph structure to dynamical phenomena.

  12. Dynamic motifs in socio-economic networks

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Shao, Shuai; Stanley, H. Eugene; Havlin, Shlomo

    2014-12-01

    Socio-economic networks are of central importance in economic life. We develop a method of identifying and studying motifs in socio-economic networks by focusing on “dynamic motifs,” i.e., evolutionary connection patterns that, because of “node acquaintances” in the network, occur much more frequently than random patterns. We examine two evolving bi-partite networks: i) the world-wide commercial ship chartering market and ii) the ship build-to-order market. We find similar dynamic motifs in both bipartite networks, even though they describe different economic activities. We also find that “influence” and “persistence” are strong factors in the interaction behavior of organizations. When two companies are doing business with the same customer, it is highly probable that another customer who currently only has business relationship with one of these two companies, will become customer of the second in the future. This is the effect of influence. Persistence means that companies with close business ties to customers tend to maintain their relationships over a long period of time.

  13. Composites

    NASA Astrophysics Data System (ADS)

    Taylor, John G.

    The Composites market is arguably the most challenging and profitable market for phenolic resins aside from electronics. The variety of products and processes encountered creates the challenges, and the demand for high performance in critical operations brings value. Phenolic composite materials are rendered into a wide range of components to supply a diverse and fragmented commercial base that includes customers in aerospace (Space Shuttle), aircraft (interiors and brakes), mass transit (interiors), defense (blast protection), marine, mine ducting, off-shore (ducts and grating) and infrastructure (architectural) to name a few. For example, phenolic resin is a critical adhesive in the manufacture of honeycomb sandwich panels. Various solvent and water based resins are described along with resin characteristics and the role of metal ions for enhanced thermal stability of the resin used to coat the honeycomb. Featured new developments include pultrusion of phenolic grating, success in RTM/VARTM fabricated parts, new ballistic developments for military vehicles and high char yield carbon-carbon composites along with many others. Additionally, global regional market resin volumes and sales are presented and compared with other thermosetting resin systems.

  14. Occurrence probability of structured motifs in random sequences.

    PubMed

    Robin, S; Daudin, J-J; Richard, H; Sagot, M-F; Schbath, S

    2002-01-01

    The problem of extracting from a set of nucleic acid sequences motifs which may have biological function is more and more important. In this paper, we are interested in particular motifs that may be implicated in the transcription process. These motifs, called structured motifs, are composed of two ordered parts separated by a variable distance and allowing for substitutions. In order to assess their statistical significance, we propose approximations of the probability of occurrences of such a structured motif in a given sequence. An application of our method to evaluate candidate promoters in E. coli and B. subtilis is presented. Simulations show the goodness of the approximations.

  15. CLIMP: Clustering Motifs via Maximal Cliques with Parallel Computing Design

    PubMed Central

    Chen, Yong

    2016-01-01

    A set of conserved binding sites recognized by a transcription factor is called a motif, which can be found by many applications of comparative genomics for identifying over-represented segments. Moreover, when numerous putative motifs are predicted from a collection of genome-wide data, their similarity data can be represented as a large graph, where these motifs are connected to one another. However, an efficient clustering algorithm is desired for clustering the motifs that belong to the same groups and separating the motifs that belong to different groups, or even deleting an amount of spurious ones. In this work, a new motif clustering algorithm, CLIMP, is proposed by using maximal cliques and sped up by parallelizing its program. When a synthetic motif dataset from the database JASPAR, a set of putative motifs from a phylogenetic foot-printing dataset, and a set of putative motifs from a ChIP dataset are used to compare the performances of CLIMP and two other high-performance algorithms, the results demonstrate that CLIMP mostly outperforms the two algorithms on the three datasets for motif clustering, so that it can be a useful complement of the clustering procedures in some genome-wide motif prediction pipelines. CLIMP is available at http://sqzhang.cn/climp.html. PMID:27487245

  16. No tradeoff between versatility and robustness in gene circuit motifs

    NASA Astrophysics Data System (ADS)

    Payne, Joshua L.

    2016-05-01

    Circuit motifs are small directed subgraphs that appear in real-world networks significantly more often than in randomized networks. In the Boolean model of gene circuits, most motifs are realized by multiple circuit genotypes. Each of a motif's constituent circuit genotypes may have one or more functions, which are embodied in the expression patterns the circuit forms in response to specific initial conditions. Recent enumeration of a space of nearly 17 million three-gene circuit genotypes revealed that all circuit motifs have more than one function, with the number of functions per motif ranging from 12 to nearly 30,000. This indicates that some motifs are more functionally versatile than others. However, the individual circuit genotypes that constitute each motif are less robust to mutation if they have many functions, hinting that functionally versatile motifs may be less robust to mutation than motifs with few functions. Here, I explore the relationship between versatility and robustness in circuit motifs, demonstrating that functionally versatile motifs are robust to mutation despite the inherent tradeoff between versatility and robustness at the level of an individual circuit genotype.

  17. RNA structural motif recognition based on least-squares distance.

    PubMed

    Shen, Ying; Wong, Hau-San; Zhang, Shaohong; Zhang, Lin

    2013-09-01

    RNA structural motifs are recurrent structural elements occurring in RNA molecules. RNA structural motif recognition aims to find RNA substructures that are similar to a query motif, and it is important for RNA structure analysis and RNA function prediction. In view of this, we propose a new method known as RNA Structural Motif Recognition based on Least-Squares distance (LS-RSMR) to effectively recognize RNA structural motifs. A test set consisting of five types of RNA structural motifs occurring in Escherichia coli ribosomal RNA is compiled by us. Experiments are conducted for recognizing these five types of motifs. The experimental results fully reveal the superiority of the proposed LS-RSMR compared with four other state-of-the-art methods.

  18. Chaotic motif sampler: detecting motifs from biological sequences by using chaotic neurodynamics

    NASA Astrophysics Data System (ADS)

    Matsuura, Takafumi; Ikeguchi, Tohru

    Identification of a region in biological sequences, motif extraction problem (MEP) is solved in bioinformatics. However, the MEP is an NP-hard problem. Therefore, it is almost impossible to obtain an optimal solution within a reasonable time frame. To find near optimal solutions for NP-hard combinatorial optimization problems such as traveling salesman problems, quadratic assignment problems, and vehicle routing problems, chaotic search, which is one of the deterministic approaches, has been proposed and exhibits better performance than stochastic approaches. In this paper, we propose a new alignment method that employs chaotic dynamics to solve the MEPs. It is called the Chaotic Motif Sampler. We show that the performance of the Chaotic Motif Sampler is considerably better than that of the conventional methods such as the Gibbs Site Sampler and the Neighborhood Optimization for Multiple Alignment Discovery.

  19. Bases of motifs for generating repeated patterns with wild cards.

    PubMed

    Pisanti, Nadia; Crochemore, Maxime; Grossi, Roberto; Sagot, Marie-France

    2005-01-01

    Motif inference represents one of the most important areas of research in computational biology, and one of its oldest ones. Despite this, the problem remains very much open in the sense that no existing definition is fully satisfying, either in formal terms, or in relation to the biological questions that involve finding such motifs. Two main types of motifs have been considered in the literature: matrices (of letter frequency per position in the motif) and patterns. There is no conclusive evidence in favor of either, and recent work has attempted to integrate the two types into a single model. In this paper, we address the formal issue in relation to motifs as patterns. This is essential to get at a better understanding of motifs in general. In particular, we consider a promising idea that was recently proposed, which attempted to avoid the combinatorial explosion in the number of motifs by means of a generator set for the motifs. Instead of exhibiting a complete list of motifs satisfying some input constraints, what is produced is a basis of such motifs from which all the other ones can be generated. We study the computational cost of determining such a basis of repeated motifs with wild cards in a sequence. We give new upper and lower bounds on such a cost, introducing a notion of basis that is provably contained in (and, thus, smaller) than previously defined ones. Our basis can be computed in less time and space, and is still able to generate the same set of motifs. We also prove that the number of motifs in all bases defined so far grows exponentially with the quorum, that is, with the minimal number of times a motif must appear in a sequence, something unnoticed in previous work. We show that there is no hope to efficiently compute such bases unless the quorum is fixed.

  20. MINER: software for phylogenetic motif identification.

    PubMed

    La, David; Livesay, Dennis R

    2005-07-01

    MINER is web-based software for phylogenetic motif (PM) identification. PMs are sequence regions (fragments) that conserve the overall familial phylogeny. PMs have been shown to correspond to a wide variety of catalytic regions, substrate-binding sites and protein interfaces, making them ideal functional site predictions. The MINER output provides an intuitive interface for interactive PM sequence analysis and structural visualization. The web implementation of MINER is freely available at http://www.pmap.csupomona.edu/MINER/. Source code is available to the academic community on request.

  1. A designed DNA binding motif that recognizes extended sites and spans two adjacent major grooves†

    PubMed Central

    Rodríguez, Jéssica; Mosquera, Jesús; García-Fandiño, Rebeca; Vázquez, M. Eugenio; Mascareñas, José L.

    2016-01-01

    We report the rational design of a DNA-binding peptide construct composed of the DNA-contacting regions of two transcription factors (GCN4 and GAGA) linked through an AT-hook DNA anchor. The resulting chimera, which represents a new, non-natural DNA binding motif, binds with high affinity and selectivity to a long composite sequence of 13 base pairs (TCAT-AATT-GAGAG). PMID:27252825

  2. Transcription factor motif quality assessment requires systematic comparative analysis

    PubMed Central

    Kibet, Caleb Kipkurui; Machanick, Philip

    2016-01-01

    Transcription factor (TF) binding site prediction remains a challenge in gene regulatory research due to degeneracy and potential variability in binding sites in the genome. Dozens of algorithms designed to learn binding models (motifs) have generated many motifs available in research papers with a subset making it to databases like JASPAR, UniPROBE and Transfac. The presence of many versions of motifs from the various databases for a single TF and the lack of a standardized assessment technique makes it difficult for biologists to make an appropriate choice of binding model and for algorithm developers to benchmark, test and improve on their models. In this study, we review and evaluate the approaches in use, highlight differences and demonstrate the difficulty of defining a standardized motif assessment approach. We review scoring functions, motif length, test data and the type of performance metrics used in prior studies as some of the factors that influence the outcome of a motif assessment. We show that the scoring functions and statistics used in motif assessment influence ranking of motifs in a TF-specific manner. We also show that TF binding specificity can vary by source of genomic binding data. We also demonstrate that information content of a motif is not in isolation a measure of motif quality but is influenced by TF binding behaviour. We conclude that there is a need for an easy-to-use tool that presents all available evidence for a comparative analysis. PMID:27092243

  3. Cross-disciplinary detection and analysis of network motifs.

    PubMed

    Tran, Ngoc Tam L; DeLuccia, Luke; McDonald, Aidan F; Huang, Chun-Hsi

    2015-01-01

    The detection of network motifs has recently become an important part of network analysis across all disciplines. In this work, we detected and analyzed network motifs from undirected and directed networks of several different disciplines, including biological network, social network, ecological network, as well as other networks such as airlines, power grid, and co-purchase of political books networks. Our analysis revealed that undirected networks are similar at the basic three and four nodes, while the analysis of directed networks revealed the distinction between networks of different disciplines. The study showed that larger motifs contained the three-node motif as a subgraph. Topological analysis revealed that similar networks have similar small motifs, but as the motif size increases, differences arise. Pearson correlation coefficient showed strong positive relationship between some undirected networks but inverse relationship between some directed networks. The study suggests that the three-node motif is a building block of larger motifs. It also suggests that undirected networks share similar low-level structures. Moreover, similar networks share similar small motifs, but larger motifs define the unique structure of individuals. Pearson correlation coefficient suggests that protein structure networks, dolphin social network, and co-authorships in network science belong to a superfamily. In addition, yeast protein-protein interaction network, primary school contact network, Zachary's karate club network, and co-purchase of political books network can be classified into a superfamily.

  4. Promoter Motifs in NCLDVs: An Evolutionary Perspective.

    PubMed

    Oliveira, Graziele Pereira; Andrade, Ana Cláudia Dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Arantes, Thalita Souza; Boratto, Paulo Victor Miranda; Silva, Ludmila Karen Dos Santos; Dornas, Fábio Pio; Trindade, Giliane de Souza; Drumond, Betânia Paiva; La Scola, Bernard; Kroon, Erna Geessien; Abrahão, Jônatas Santos

    2017-01-20

    For many years, gene expression in the three cellular domains has been studied in an attempt to discover sequences associated with the regulation of the transcription process. Some specific transcriptional features were described in viruses, although few studies have been devoted to understanding the evolutionary aspects related to the spread of promoter motifs through related viral families. The discovery of giant viruses and the proposition of the new viral order Megavirales that comprise a monophyletic group, named nucleo-cytoplasmic large DNA viruses (NCLDV), raised new questions in the field. Some putative promoter sequences have already been described for some NCLDV members, bringing new insights into the evolutionary history of these complex microorganisms. In this review, we summarize the main aspects of the transcription regulation process in the three domains of life, followed by a systematic description of what is currently known about promoter regions in several NCLDVs. We also discuss how the analysis of the promoter sequences could bring new ideas about the giant viruses' evolution. Finally, considering a possible common ancestor for the NCLDV group, we discussed possible promoters' evolutionary scenarios and propose the term "MEGA-box" to designate an ancestor promoter motif ('TATATAAAATTGA') that could be evolved gradually by nucleotides' gain and loss and point mutations.

  5. Motif-directed redesign of enzyme specificity.

    PubMed

    Borgo, Benjamin; Havranek, James J

    2014-03-01

    Computational protein design relies on several approximations, including the use of fixed backbones and rotamers, to reduce protein design to a computationally tractable problem. However, allowing backbone and off-rotamer flexibility leads to more accurate designs and greater conformational diversity. Exhaustive sampling of this additional conformational space is challenging, and often impossible. Here, we report a computational method that utilizes a preselected library of native interactions to direct backbone flexibility to accommodate placement of these functional contacts. Using these native interaction modules, termed motifs, improves the likelihood that the interaction can be realized, provided that suitable backbone perturbations can be identified. Furthermore, it allows a directed search of the conformational space, reducing the sampling needed to find low energy conformations. We implemented the motif-based design algorithm in Rosetta, and tested the efficacy of this method by redesigning the substrate specificity of methionine aminopeptidase. In summary, native enzymes have evolved to catalyze a wide range of chemical reactions with extraordinary specificity. Computational enzyme design seeks to generate novel chemical activities by altering the target substrates of these existing enzymes. We have implemented a novel approach to redesign the specificity of an enzyme and demonstrated its effectiveness on a model system.

  6. Promoter Motifs in NCLDVs: An Evolutionary Perspective

    PubMed Central

    Oliveira, Graziele Pereira; Andrade, Ana Cláudia dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Arantes, Thalita Souza; Boratto, Paulo Victor Miranda; Silva, Ludmila Karen dos Santos; Dornas, Fábio Pio; Trindade, Giliane de Souza; Drumond, Betânia Paiva; La Scola, Bernard; Kroon, Erna Geessien; Abrahão, Jônatas Santos

    2017-01-01

    For many years, gene expression in the three cellular domains has been studied in an attempt to discover sequences associated with the regulation of the transcription process. Some specific transcriptional features were described in viruses, although few studies have been devoted to understanding the evolutionary aspects related to the spread of promoter motifs through related viral families. The discovery of giant viruses and the proposition of the new viral order Megavirales that comprise a monophyletic group, named nucleo-cytoplasmic large DNA viruses (NCLDV), raised new questions in the field. Some putative promoter sequences have already been described for some NCLDV members, bringing new insights into the evolutionary history of these complex microorganisms. In this review, we summarize the main aspects of the transcription regulation process in the three domains of life, followed by a systematic description of what is currently known about promoter regions in several NCLDVs. We also discuss how the analysis of the promoter sequences could bring new ideas about the giant viruses’ evolution. Finally, considering a possible common ancestor for the NCLDV group, we discussed possible promoters’ evolutionary scenarios and propose the term “MEGA-box” to designate an ancestor promoter motif (‘TATATAAAATTGA’) that could be evolved gradually by nucleotides’ gain and loss and point mutations. PMID:28117683

  7. Probabilistic models for semisupervised discriminative motif discovery in DNA sequences.

    PubMed

    Kim, Jong Kyoung; Choi, Seungjin

    2011-01-01

    Methods for discriminative motif discovery in DNA sequences identify transcription factor binding sites (TFBSs), searching only for patterns that differentiate two sets (positive and negative sets) of sequences. On one hand, discriminative methods increase the sensitivity and specificity of motif discovery, compared to generative models. On the other hand, generative models can easily exploit unlabeled sequences to better detect functional motifs when labeled training samples are limited. In this paper, we develop a hybrid generative/discriminative model which enables us to make use of unlabeled sequences in the framework of discriminative motif discovery, leading to semisupervised discriminative motif discovery. Numerical experiments on yeast ChIP-chip data for discovering DNA motifs demonstrate that the best performance is obtained between the purely-generative and the purely-discriminative and the semisupervised learning improves the performance when labeled sequences are limited.

  8. An Affinity Propagation-Based DNA Motif Discovery Algorithm.

    PubMed

    Sun, Chunxiao; Huo, Hongwei; Yu, Qiang; Guo, Haitao; Sun, Zhigang

    2015-01-01

    The planted (l, d) motif search (PMS) is one of the fundamental problems in bioinformatics, which plays an important role in locating transcription factor binding sites (TFBSs) in DNA sequences. Nowadays, identifying weak motifs and reducing the effect of local optimum are still important but challenging tasks for motif discovery. To solve the tasks, we propose a new algorithm, APMotif, which first applies the Affinity Propagation (AP) clustering in DNA sequences to produce informative and good candidate motifs and then employs Expectation Maximization (EM) refinement to obtain the optimal motifs from the candidate motifs. Experimental results both on simulated data sets and real biological data sets show that APMotif usually outperforms four other widely used algorithms in terms of high prediction accuracy.

  9. Network Motifs: Simple Building Blocks of Complex Networks

    NASA Astrophysics Data System (ADS)

    Milo, R.; Shen-Orr, S.; Itzkovitz, S.; Kashtan, N.; Chklovskii, D.; Alon, U.

    2002-10-01

    Complex networks are studied across many fields of science. To uncover their structural design principles, we defined ``network motifs,'' patterns of interconnections occurring in complex networks at numbers that are significantly higher than those in randomized networks. We found such motifs in networks from biochemistry, neurobiology, ecology, and engineering. The motifs shared by ecological food webs were distinct from the motifs shared by the genetic networks of Escherichia coli and Saccharomyces cerevisiae or from those found in the World Wide Web. Similar motifs were found in networks that perform information processing, even though they describe elements as different as biomolecules within a cell and synaptic connections between neurons in Caenorhabditis elegans. Motifs may thus define universal classes of networks. This approach may uncover the basic building blocks of most networks.

  10. Detecting DNA regulatory motifs by incorporating positional trendsin information content

    SciTech Connect

    Kechris, Katherina J.; van Zwet, Erik; Bickel, Peter J.; Eisen,Michael B.

    2004-05-04

    On the basis of the observation that conserved positions in transcription factor binding sites are often clustered together, we propose a simple extension to the model-based motif discovery methods. We assign position-specific prior distributions to the frequency parameters of the model, penalizing deviations from a specified conservation profile. Examples with both simulated and real data show that this extension helps discover motifs as the data become noisier or when there is a competing false motif.

  11. A Multi-Scale Framework for Multi-Field Analyses of Smart Composites

    DTIC Science & Technology

    2015-01-15

    AFRL-OSR-VA-TR-2015-0034 A MULTI--SCALE FRAMEWORK FOR MULTI-- FIELD ANALYSES OF SMART COMPOS Anastasia Muliana TEXAS ENGINEERING EXPERIMENT STATION...Oct 15, 2009-Oct 14 2014 4. TITLE AND SUBTITLE AFOSR PECASE Grant A multi-scale framework for multi- field analyses of smart composites 5a. CONTRACT...mechanical responses, including loading rate (time) effect, of the constituents (piezoelectric ceramics and polymers) on the overall multi- field responses

  12. Gibbs motif sampling: detection of bacterial outer membrane protein repeats.

    PubMed Central

    Neuwald, A. F.; Liu, J. S.; Lawrence, C. E.

    1995-01-01

    The detection and alignment of locally conserved regions (motifs) in multiple sequences can provide insight into protein structure, function, and evolution. A new Gibbs sampling algorithm is described that detects motif-encoding regions in sequences and optimally partitions them into distinct motif models; this is illustrated using a set of immunoglobulin fold proteins. When applied to sequences sharing a single motif, the sampler can be used to classify motif regions into related submodels, as is illustrated using helix-turn-helix DNA-binding proteins. Other statistically based procedures are described for searching a database for sequences matching motifs found by the sampler. When applied to a set of 32 very distantly related bacterial integral outer membrane proteins, the sampler revealed that they share a subtle, repetitive motif. Although BLAST (Altschul SF et al., 1990, J Mol Biol 215:403-410) fails to detect significant pairwise similarity between any of the sequences, the repeats present in these outer membrane proteins, taken as a whole, are highly significant (based on a generally applicable statistical test for motifs described here). Analysis of bacterial porins with known trimeric beta-barrel structure and related proteins reveals a similar repetitive motif corresponding to alternating membrane-spanning beta-strands. These beta-strands occur on the membrane interface (as opposed to the trimeric interface) of the beta-barrel. The broad conservation and structural location of these repeats suggests that they play important functional roles. PMID:8520488

  13. Discriminative motif analysis of high-throughput dataset

    PubMed Central

    Yao, Zizhen; MacQuarrie, Kyle L.; Fong, Abraham P.; Tapscott, Stephen J.; Ruzzo, Walter L.; Gentleman, Robert C.

    2014-01-01

    Motivation: High-throughput ChIP-seq studies typically identify thousands of peaks for a single transcription factor (TF). It is common for traditional motif discovery tools to predict motifs that are statistically significant against a naïve background distribution but are of questionable biological relevance. Results: We describe a simple yet effective algorithm for discovering differential motifs between two sequence datasets that is effective in eliminating systematic biases and scalable to large datasets. Tested on 207 ENCODE ChIP-seq datasets, our method identifies correct motifs in 78% of the datasets with known motifs, demonstrating improvement in both accuracy and efficiency compared with DREME, another state-of-art discriminative motif discovery tool. More interestingly, on the remaining more challenging datasets, we identify common technical or biological factors that compromise the motif search results and use advanced features of our tool to control for these factors. We also present case studies demonstrating the ability of our method to detect single base pair differences in DNA specificity of two similar TFs. Lastly, we demonstrate discovery of key TF motifs involved in tissue specification by examination of high-throughput DNase accessibility data. Availability: The motifRG package is publically available via the bioconductor repository. Contact: yzizhen@fhcrc.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24162561

  14. An RNA motif that binds ATP

    NASA Technical Reports Server (NTRS)

    Sassanfar, M.; Szostak, J. W.

    1993-01-01

    RNAs that contain specific high-affinity binding sites for small molecule ligands immobilized on a solid support are present at a frequency of roughly one in 10(10)-10(11) in pools of random sequence RNA molecules. Here we describe a new in vitro selection procedure designed to ensure the isolation of RNAs that bind the ligand of interest in solution as well as on a solid support. We have used this method to isolate a remarkably small RNA motif that binds ATP, a substrate in numerous biological reactions and the universal biological high-energy intermediate. The selected ATP-binding RNAs contain a consensus sequence, embedded in a common secondary structure. The binding properties of ATP analogues and modified RNAs show that the binding interaction is characterized by a large number of close contacts between the ATP and RNA, and by a change in the conformation of the RNA.

  15. Complex lasso: new entangled motifs in proteins

    NASA Astrophysics Data System (ADS)

    Niemyska, Wanda; Dabrowski-Tumanski, Pawel; Kadlof, Michal; Haglund, Ellinor; Sułkowski, Piotr; Sulkowska, Joanna I.

    2016-11-01

    We identify new entangled motifs in proteins that we call complex lassos. Lassos arise in proteins with disulfide bridges (or in proteins with amide linkages), when termini of a protein backbone pierce through an auxiliary surface of minimal area, spanned on a covalent loop. We find that as much as 18% of all proteins with disulfide bridges in a non-redundant subset of PDB form complex lassos, and classify them into six distinct geometric classes, one of which resembles supercoiling known from DNA. Based on biological classification of proteins we find that lassos are much more common in viruses, plants and fungi than in other kingdoms of life. We also discuss how changes in the oxidation/reduction potential may affect the function of proteins with lassos. Lassos and associated surfaces of minimal area provide new, interesting and possessing many potential applications geometric characteristics not only of proteins, but also of other biomolecules.

  16. Complex lasso: new entangled motifs in proteins

    PubMed Central

    Niemyska, Wanda; Dabrowski-Tumanski, Pawel; Kadlof, Michal; Haglund, Ellinor; Sułkowski, Piotr; Sulkowska, Joanna I.

    2016-01-01

    We identify new entangled motifs in proteins that we call complex lassos. Lassos arise in proteins with disulfide bridges (or in proteins with amide linkages), when termini of a protein backbone pierce through an auxiliary surface of minimal area, spanned on a covalent loop. We find that as much as 18% of all proteins with disulfide bridges in a non-redundant subset of PDB form complex lassos, and classify them into six distinct geometric classes, one of which resembles supercoiling known from DNA. Based on biological classification of proteins we find that lassos are much more common in viruses, plants and fungi than in other kingdoms of life. We also discuss how changes in the oxidation/reduction potential may affect the function of proteins with lassos. Lassos and associated surfaces of minimal area provide new, interesting and possessing many potential applications geometric characteristics not only of proteins, but also of other biomolecules. PMID:27874096

  17. A Novel Method for Dynamic Short-Beam Shear Testing of 3D Woven Composites

    DTIC Science & Technology

    2011-08-11

    Yip MC, Lin JL (1998) Effects of low-energy impact on the fatigue behavior of carbon /epoxy composites. Composites Science and Technology 58(1):1–8 5...Compos- ite Materials 42(20):2111–2122 12. Davis DC, Whelan BD (2012) An experimental study of interlam- inar shear fracture toughness of a nanotube ...delamination toughness of stitched graphite/epoxy textile composites. Composites Science and Technology 57(7):729–737 15. Chen L, Ifju PG, Sankar BV (2001) A

  18. Motif-role-fingerprints: the building-blocks of motifs, clustering-coefficients and transitivities in directed networks.

    PubMed

    McDonnell, Mark D; Yaveroğlu, Ömer Nebil; Schmerl, Brett A; Iannella, Nicolangelo; Ward, Lawrence M

    2014-01-01

    Complex networks are frequently characterized by metrics for which particular subgraphs are counted. One statistic from this category, which we refer to as motif-role fingerprints, differs from global subgraph counts in that the number of subgraphs in which each node participates is counted. As with global subgraph counts, it can be important to distinguish between motif-role fingerprints that are 'structural' (induced subgraphs) and 'functional' (partial subgraphs). Here we show mathematically that a vector of all functional motif-role fingerprints can readily be obtained from an arbitrary directed adjacency matrix, and then converted to structural motif-role fingerprints by multiplying that vector by a specific invertible conversion matrix. This result demonstrates that a unique structural motif-role fingerprint exists for any given functional motif-role fingerprint. We demonstrate a similar result for the cases of functional and structural motif-fingerprints without node roles, and global subgraph counts that form the basis of standard motif analysis. We also explicitly highlight that motif-role fingerprints are elemental to several popular metrics for quantifying the subgraph structure of directed complex networks, including motif distributions, directed clustering coefficient, and transitivity. The relationships between each of these metrics and motif-role fingerprints also suggest new subtypes of directed clustering coefficients and transitivities. Our results have potential utility in analyzing directed synaptic networks constructed from neuronal connectome data, such as in terms of centrality. Other potential applications include anomaly detection in networks, identification of similar networks and identification of similar nodes within networks. Matlab code for calculating all stated metrics following calculation of functional motif-role fingerprints is provided as S1 Matlab File.

  19. Motif-Role-Fingerprints: The Building-Blocks of Motifs, Clustering-Coefficients and Transitivities in Directed Networks

    PubMed Central

    McDonnell, Mark D.; Yaveroğlu, Ömer Nebil; Schmerl, Brett A.; Iannella, Nicolangelo; Ward, Lawrence M.

    2014-01-01

    Complex networks are frequently characterized by metrics for which particular subgraphs are counted. One statistic from this category, which we refer to as motif-role fingerprints, differs from global subgraph counts in that the number of subgraphs in which each node participates is counted. As with global subgraph counts, it can be important to distinguish between motif-role fingerprints that are ‘structural’ (induced subgraphs) and ‘functional’ (partial subgraphs). Here we show mathematically that a vector of all functional motif-role fingerprints can readily be obtained from an arbitrary directed adjacency matrix, and then converted to structural motif-role fingerprints by multiplying that vector by a specific invertible conversion matrix. This result demonstrates that a unique structural motif-role fingerprint exists for any given functional motif-role fingerprint. We demonstrate a similar result for the cases of functional and structural motif-fingerprints without node roles, and global subgraph counts that form the basis of standard motif analysis. We also explicitly highlight that motif-role fingerprints are elemental to several popular metrics for quantifying the subgraph structure of directed complex networks, including motif distributions, directed clustering coefficient, and transitivity. The relationships between each of these metrics and motif-role fingerprints also suggest new subtypes of directed clustering coefficients and transitivities. Our results have potential utility in analyzing directed synaptic networks constructed from neuronal connectome data, such as in terms of centrality. Other potential applications include anomaly detection in networks, identification of similar networks and identification of similar nodes within networks. Matlab code for calculating all stated metrics following calculation of functional motif-role fingerprints is provided as S1 Matlab File. PMID:25486535

  20. Mitochondrial and Y chromosome haplotype motifs as diagnostic markers of Jewish ancestry: a reconsideration.

    PubMed

    Tofanelli, Sergio; Taglioli, Luca; Bertoncini, Stefania; Francalacci, Paolo; Klyosov, Anatole; Pagani, Luca

    2014-01-01

    Several authors have proposed haplotype motifs based on site variants at the mitochondrial genome (mtDNA) and the non-recombining portion of the Y chromosome (NRY) to trace the genealogies of Jewish people. Here, we analyzed their main approaches and test the feasibility of adopting motifs as ancestry markers through construction of a large database of mtDNA and NRY haplotypes from public genetic genealogical repositories. We verified the reliability of Jewish ancestry prediction based on the Cohen and Levite Modal Haplotypes in their "classical" 6 STR marker format or in the "extended" 12 STR format, as well as four founder mtDNA lineages (HVS-I segments) accounting for about 40% of the current population of Ashkenazi Jews. For this purpose we compared haplotype composition in individuals of self-reported Jewish ancestry with the rest of European, African or Middle Eastern samples, to test for non-random association of ethno-geographic groups and haplotypes. Overall, NRY and mtDNA based motifs, previously reported to differentiate between groups, were found to be more represented in Jewish compared to non-Jewish groups. However, this seems to stem from common ancestors of Jewish lineages being rather recent respect to ancestors of non-Jewish lineages with the same "haplotype signatures." Moreover, the polyphyly of haplotypes which contain the proposed motifs and the misuse of constant mutation rates heavily affected previous attempts to correctly dating the origin of common ancestries. Accordingly, our results stress the limitations of using the above haplotype motifs as reliable Jewish ancestry predictors and show its inadequacy for forensic or genealogical purposes.

  1. MADMX: a strategy for maximal dense motif extraction.

    PubMed

    Grossi, Roberto; Pietracaprina, Andrea; Pisanti, Nadia; Pucci, Geppino; Upfal, Eli; Vandin, Fabio

    2011-04-01

    We develop, analyze, and experiment with a new tool, called MADMX, which extracts frequent motifs from biological sequences. We introduce the notion of density to single out the "significant" motifs. The density is a simple and flexible measure for bounding the number of don't cares in a motif, defined as the fraction of solid (i.e., different from don't care) characters in the motif. A maximal dense motif has density above a certain threshold, and any further specialization of a don't care symbol in it or any extension of its boundaries decreases its number of occurrences in the input sequence. By extracting only maximal dense motifs, MADMX reduces the output size and improves performance, while enhancing the quality of the discoveries. The efficiency of our approach relies on a newly defined combining operation, dubbed fusion, which allows for the construction of maximal dense motifs in a bottom-up fashion, while avoiding the generation of nonmaximal ones. We provide experimental evidence of the efficiency and the quality of the motifs returned by MADMX.

  2. DETAIL VIEW, MAIN ENTRANCE GATES, SHOWING A WINGED HOURGLASS MOTIF, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW, MAIN ENTRANCE GATES, SHOWING A WINGED HOURGLASS MOTIF, WHICH REFERS TO THE QUICK PASSAGE OF TIME AND THE SHORTNESS OF HUMAN LIFE. USE OF THIS MOTIF WAS A CARRYOVER FROM THE MCARTHUR GATES. - Woodlands Cemetery, 4000 Woodlands Avenue, Philadelphia, Philadelphia County, PA

  3. Dynamic motifs of strategies in prisoner's dilemma games

    NASA Astrophysics Data System (ADS)

    Kim, Young Jin; Roh, Myungkyoon; Jeong, Seon-Young; Son, Seung-Woo

    2014-12-01

    We investigate the win-lose relations between strategies of iterated prisoner's dilemma games by using a directed network concept to display the replicator dynamics results. In the giant strongly-connected component of the win/lose network, we find win-lose circulations similar to rock-paper-scissors and analyze the fixed point and its stability. Applying the network motif concept, we introduce dynamic motifs, which describe the population dynamics relations among the three strategies. Through exact enumeration, we find 22 dynamic motifs and display their phase portraits. Visualization using directed networks and motif analysis is a useful method to make complex dynamic behavior simple in order to understand it more intuitively. Dynamic motifs can be building blocks for dynamic behavior among strategies when they are applied to other types of games.

  4. Crossover among structural motifs in Pd-Au nanoalloys.

    PubMed

    Zhu, Beien; Guesmi, Hazar; Creuze, Jérôme; Legrand, Bernard; Mottet, Christine

    2015-11-14

    The crossovers among the most abundant structural motifs (icosahedra, decahedra and truncated octahedra) of Pd-Au nanoalloys have been determined theoretically in a size range between 2 and 7 nm and for three compositions equivalent to Pd3Au, PdAu and PdAu3. The chemical ordering and segregation optimisation are performed via Monte Carlo simulations using semi-empirical tight-binding potentials fitted to ab initio calculations. The chemical configurations are then quenched via molecular dynamic simulations in order to compare their energy and characterize the equilibrium structures as a function of the cluster size. For the smaller sizes (of around 300 atoms and fewer) the structures are also optimized at the electronic level within ab initio calculations in order to validate the semi-empirical potential. The predictions of the crossover sizes for the nanoalloys cannot be simply extrapolated from the crossover of the pure nanoparticles but imply stress release phenomena related to the size misfit between the two metals. Indeed, alloying extends the range of stability of the icosahedron beyond that of the pure systems and the energy differences between decahedra and truncated octahedra become asymptotic, around the sizes of 5-6 nm. Nevertheless, such equilibrium results should be modulated regarding kinetic considerations or possible gas adsorption under experimental conditions.

  5. De Novo Regulatory Motif Discovery Identifies Significant Motifs in Promoters of Five Classes of Plant Dehydrin Genes

    PubMed Central

    Zolotarov, Yevgen; Strömvik, Martina

    2015-01-01

    Plants accumulate dehydrins in response to osmotic stresses. Dehydrins are divided into five different classes, which are thought to be regulated in different manners. To better understand differences in transcriptional regulation of the five dehydrin classes, de novo motif discovery was performed on 350 dehydrin promoter sequences from a total of 51 plant genomes. Overrepresented motifs were identified in the promoters of five dehydrin classes. The Kn dehydrin promoters contain motifs linked with meristem specific expression, as well as motifs linked with cold/dehydration and abscisic acid response. KS dehydrin promoters contain a motif with a GATA core. SKn and YnSKn dehydrin promoters contain motifs that match elements connected with cold/dehydration, abscisic acid and light response. YnKn dehydrin promoters contain motifs that match abscisic acid and light response elements, but not cold/dehydration response elements. Conserved promoter motifs are present in the dehydrin classes and across different plant lineages, indicating that dehydrin gene regulation is likely also conserved. PMID:26114291

  6. Single promoters as regulatory network motifs

    NASA Astrophysics Data System (ADS)

    Zopf, Christopher; Maheshri, Narendra

    2012-02-01

    At eukaryotic promoters, chromatin can influence the relationship between a gene's expression and transcription factor (TF) activity. This additional complexity might allow single promoters to exhibit dynamical behavior commonly attributed to regulatory motifs involving multiple genes. We investigate the role of promoter chromatin architecture in the kinetics of gene activation using a previously described set of promoter variants based on the phosphate-regulated PHO5 promoter in S. cerevisiae. Accurate quantitative measurement of transcription activation kinetics is facilitated by a controllable and observable TF input to a promoter of interest leading to an observable expression output in single cells. We find the particular architecture of these promoters can result in a significant delay in activation, filtering of noisy TF signals, and a memory of previous activation -- dynamical behaviors reminiscent of a feed-forward loop but only requiring a single promoter. We suggest this is a consequence of chromatin transactions at the promoter, likely passing through a long-lived ``primed'' state between its inactive and competent states. Finally, we show our experimental setup can be generalized as a ``gene oscilloscope'' to probe the kinetics of heterologous promoter architectures.

  7. Triadic motifs in the dependence networks of virtual societies.

    PubMed

    Xie, Wen-Jie; Li, Ming-Xia; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-06-10

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs.

  8. Triadic motifs in the dependence networks of virtual societies

    PubMed Central

    Xie, Wen-Jie; Li, Ming-Xia; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-01-01

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs. PMID:24912755

  9. The TRTGn motif stabilizes the transcription initiation open complex.

    PubMed

    Voskuil, Martin I; Chambliss, Glenn H

    2002-09-20

    The effect on transcription initiation by the extended -10 motif (5'-TRTG(n)-3'), positioned upstream of the -10 region, was investigated using a series of base substitution mutations in the alpha-amylase promoter (amyP). The extended -10 motif, previously referred to as the -16 region, is found frequently in Gram-positive bacterial promoters and several extended -10 promoters from Escherichia coli. The inhibitory effects of the non-productive promoter site (amyP2), which overlaps the upstream region of amyP, were eliminated by mutagenesis of the -35 region and the TRTG motif of amyP2. Removal by mutagenesis of the competitive effects of amyP2 resulted in a reduced dependence of amyP on the TRTG motif. In the absence of the second promoter, mutations in the TRTG motif of amyP destabilized the open complex and prevented the maintenance of open complexes at low temperatures. The open complex half-life was up to 26-fold shorter in the mutant TRTG motif promoters than in the wild-type promoter. We demonstrate that the amyP TRTG motif dramatically stabilizes the open complex intermediate during transcription initiation. Even though the open complex is less stable in the mutant promoters, the region of melted DNA is the same in the wild-type and mutant promoters. However, upon addition of the first three nucleotides, which trap RNAP (RNA polymerase) in a stable initiating complex, the melted DNA region contracts at the 5'-end in a TRTG motif promoter mutant but not at the wild-type promoter, indicating that the motif contributes to maintaining DNA-strand separation.

  10. Automated motif extraction and classification in RNA tertiary structures

    PubMed Central

    Djelloul, Mahassine; Denise, Alain

    2008-01-01

    We used a novel graph-based approach to extract RNA tertiary motifs. We cataloged them all and clustered them using an innovative graph similarity measure. We applied our method to three widely studied structures: Haloarcula marismortui 50S (H.m 50S), Escherichia coli 50S (E. coli 50S), and Thermus thermophilus 16S (T.th 16S) RNAs. We identified 10 known motifs without any prior knowledge of their shapes or positions. We additionally identified four putative new motifs. PMID:18957493

  11. Coherent feedforward transcriptional regulatory motifs enhance drug resistance

    NASA Astrophysics Data System (ADS)

    Charlebois, Daniel A.; Balázsi, Gábor; Kærn, Mads

    2014-05-01

    Fluctuations in gene expression give identical cells access to a spectrum of phenotypes that can serve as a transient, nongenetic basis for natural selection by temporarily increasing drug resistance. In this study, we demonstrate using mathematical modeling and simulation that certain gene regulatory network motifs, specifically coherent feedforward loop motifs, can facilitate the development of nongenetic resistance by increasing cell-to-cell variability and the time scale at which beneficial phenotypic states can be maintained. Our results highlight how regulatory network motifs enabling transient, nongenetic inheritance play an important role in defining reproductive fitness in adverse environments and provide a selective advantage subject to evolutionary pressure.

  12. Targeting functional motifs of a protein family

    NASA Astrophysics Data System (ADS)

    Bhadola, Pradeep; Deo, Nivedita

    2016-10-01

    The structural organization of a protein family is investigated by devising a method based on the random matrix theory (RMT), which uses the physiochemical properties of the amino acid with multiple sequence alignment. A graphical method to represent protein sequences using physiochemical properties is devised that gives a fast, easy, and informative way of comparing the evolutionary distances between protein sequences. A correlation matrix associated with each property is calculated, where the noise reduction and information filtering is done using RMT involving an ensemble of Wishart matrices. The analysis of the eigenvalue statistics of the correlation matrix for the β -lactamase family shows the universal features as observed in the Gaussian orthogonal ensemble (GOE). The property-based approach captures the short- as well as the long-range correlation (approximately following GOE) between the eigenvalues, whereas the previous approach (treating amino acids as characters) gives the usual short-range correlations, while the long-range correlations are the same as that of an uncorrelated series. The distribution of the eigenvector components for the eigenvalues outside the bulk (RMT bound) deviates significantly from RMT observations and contains important information about the system. The information content of each eigenvector of the correlation matrix is quantified by introducing an entropic estimate, which shows that for the β -lactamase family the smallest eigenvectors (low eigenmodes) are highly localized as well as informative. These small eigenvectors when processed gives clusters involving positions that have well-defined biological and structural importance matching with experiments. The approach is crucial for the recognition of structural motifs as shown in β -lactamase (and other families) and selectively identifies the important positions for targets to deactivate (activate) the enzymatic actions.

  13. Targeting functional motifs of a protein family.

    PubMed

    Bhadola, Pradeep; Deo, Nivedita

    2016-10-01

    The structural organization of a protein family is investigated by devising a method based on the random matrix theory (RMT), which uses the physiochemical properties of the amino acid with multiple sequence alignment. A graphical method to represent protein sequences using physiochemical properties is devised that gives a fast, easy, and informative way of comparing the evolutionary distances between protein sequences. A correlation matrix associated with each property is calculated, where the noise reduction and information filtering is done using RMT involving an ensemble of Wishart matrices. The analysis of the eigenvalue statistics of the correlation matrix for the β-lactamase family shows the universal features as observed in the Gaussian orthogonal ensemble (GOE). The property-based approach captures the short- as well as the long-range correlation (approximately following GOE) between the eigenvalues, whereas the previous approach (treating amino acids as characters) gives the usual short-range correlations, while the long-range correlations are the same as that of an uncorrelated series. The distribution of the eigenvector components for the eigenvalues outside the bulk (RMT bound) deviates significantly from RMT observations and contains important information about the system. The information content of each eigenvector of the correlation matrix is quantified by introducing an entropic estimate, which shows that for the β-lactamase family the smallest eigenvectors (low eigenmodes) are highly localized as well as informative. These small eigenvectors when processed gives clusters involving positions that have well-defined biological and structural importance matching with experiments. The approach is crucial for the recognition of structural motifs as shown in β-lactamase (and other families) and selectively identifies the important positions for targets to deactivate (activate) the enzymatic actions.

  14. Thermodynamic Features of Structural Motifs Formed by β-L-RNA

    PubMed Central

    Szabat, Marta; Gudanis, Dorota; Kotkowiak, Weronika; Gdaniec, Zofia; Kierzek, Ryszard; Pasternak, Anna

    2016-01-01

    This is the first report to provide comprehensive thermodynamic and structural data concerning duplex, hairpin, quadruplex and i-motif structures in β-L-RNA series. Herein we confirm that, within the limits of experimental error, the thermodynamic stability of enantiomeric structural motifs is the same as that of naturally occurring D-RNA counterparts. In addition, formation of D-RNA/L-RNA heterochiral duplexes is also observed; however, their thermodynamic stability is significantly reduced in reference to homochiral D-RNA duplexes. The presence of three locked nucleic acid (LNA) residues within the D-RNA strand diminishes the negative effect of the enantiomeric, complementary L-RNA strand in the formation of heterochiral RNA duplexes. Similar behavior is also observed for heterochiral LNA-2′-O-methyl-D-RNA/L-RNA duplexes. The formation of heterochiral duplexes was confirmed by 1H NMR spectroscopy. The CD curves of homochiral L-RNA structural motifs are always reversed, whereas CD curves of heterochiral duplexes present individual features dependent on the composition of chiral strands. PMID:26908023

  15. A million peptide motifs for the molecular biologist.

    PubMed

    Tompa, Peter; Davey, Norman E; Gibson, Toby J; Babu, M Madan

    2014-07-17

    A molecular description of functional modules in the cell is the focus of many high-throughput studies in the postgenomic era. A large portion of biomolecular interactions in virtually all cellular processes is mediated by compact interaction modules, referred to as peptide motifs. Such motifs are typically less than ten residues in length, occur within intrinsically disordered regions, and are recognized and/or posttranslationally modified by structured domains of the interacting partner. In this review, we suggest that there might be over a million instances of peptide motifs in the human proteome. While this staggering number suggests that peptide motifs are numerous and the most understudied functional module in the cell, it also holds great opportunities for new discoveries.

  16. DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT SHADES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT SHADES OF GOLD LEAF AND BURNISHED GOLD LEAF WERE USED FOR THE INTERIOR FINISHES. - Anaconda Historic District, Washoe Theater, 305 Main Street, Anaconda, Deer Lodge County, MT

  17. 10. DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT SHADES OF GOLD LEAF AND BURNISHED GOLD LEAF WERE USED FOR THE INTERIOR FINISHES - Anaconda Historic District, Washoe Theater, 305 Main Street, Anaconda, Deer Lodge County, MT

  18. Three-Dimensional DNA Nanostructures Assembled from DNA Star Motifs.

    PubMed

    Tian, Cheng; Zhang, Chuan

    2017-01-01

    Tile-based DNA self-assembly is a promising method in DNA nanotechnology and has produced a wide range of nanostructures by using a small set of unique DNA strands. DNA star motif, as one of DNA tiles, has been employed to assemble varieties of symmetric one-, two-, three-dimensional (1, 2, 3D) DNA nanostructures. Herein, we describe the design principles, assembly methods, and characterization methods of 3D DNA nanostructures assembled from the DNA star motifs.

  19. Finding specific RNA motifs: Function in a zeptomole world?

    PubMed Central

    KNIGHT, ROB; YARUS, MICHAEL

    2003-01-01

    We have developed a new method for estimating the abundance of any modular (piecewise) RNA motif within a longer random region. We have used this method to estimate the size of the active motifs available to modern SELEX experiments (picomoles of unique sequences) and to a plausible RNA World (zeptomoles of unique sequences: 1 zmole = 602 sequences). Unexpectedly, activities such as specific isoleucine binding are almost certainly present in zeptomoles of molecules, and even ribozymes such as self-cleavage motifs may appear (depending on assumptions about the minimal structures). The number of specified nucleotides is not the only important determinant of a motif’s rarity: The number of modules into which it is divided, and the details of this division, are also crucial. We propose three maxims for easily isolated motifs: the Maxim of Minimization, the Maxim of Multiplicity, and the Maxim of the Median. These maxims together state that selected motifs should be small and composed of as many separate, equally sized modules as possible. For evenly divided motifs with four modules, the largest accessible activity in picomole scale (1–1000 pmole) pools of length 100 is about 34 nucleotides; while for zeptomole scale (1–1000 zmole) pools it is about 20 specific nucleotides (50% probability of occurrence). This latter figure includes some ribozymes and aptamers. Consequently, an RNA metabolism apparently could have begun with only zeptomoles of RNA molecules. PMID:12554865

  20. Selection of peptide entry motifs by bacterial surface display.

    PubMed Central

    Taschner, Sabine; Meinke, Andreas; von Gabain, Alexander; Boyd, Aoife P

    2002-01-01

    Surface display technologies have been established previously to select peptides and polypeptides that interact with purified immobilized ligands. In the present study, we designed and implemented a surface display-based technique to identify novel peptide motifs that mediate entry into eukaryotic cells. An Escherichia coli library expressing surface-displayed peptides was combined with eukaryotic cells and the gentamicin protection assay was performed to select recombinant E. coli, which were internalized into eukaryotic cells by virtue of the displayed peptides. To establish the proof of principle of this approach, the fibronectin-binding motifs of the fibronectin-binding protein A of Staphylococcus aureus were inserted into the E. coli FhuA protein. Surface expression of the fusion proteins was demonstrated by functional assays and by FACS analysis. The fibronectin-binding motifs were shown to mediate entry of the bacteria into non-phagocytic eukaryotic cells and brought about the preferential selection of these bacteria over E. coli expressing parental FhuA, with an enrichment of 100000-fold. Four entry sequences were selected and identified using an S. aureus library of peptides displayed in the FhuA protein on the surface of E. coli. These sequences included novel entry motifs as well as integrin-binding Arg-Gly-Asp (RGD) motifs and promoted a high degree of bacterial entry. Bacterial surface display is thus a powerful tool to effectively select and identify entry peptide motifs. PMID:12144529

  1. Discovering Multidimensional Motifs in Physiological Signals for Personalized Healthcare.

    PubMed

    Balasubramanian, Arvind; Wang, Jun; Prabhakaran, Balakrishnan

    2016-08-01

    Personalized diagnosis and therapy requires monitoring patient activity using various body sensors. Sensor data generated during personalized exercises or tasks may be too specific or inadequate to be evaluated using supervised methods such as classification. We propose multidimensional motif (MDM) discovery as a means for patient activity monitoring, since such motifs can capture repeating patterns across multiple dimensions of the data, and can serve as conformance indicators. Previous studies pertaining to mining MDMs have proposed approaches that lack the capability of concurrently processing multiple dimensions, thus limiting their utility in online scenarios. In this paper, we propose an efficient real-time approach to MDM discovery in body sensor generated time series data for monitoring performance of patients during therapy. We present two alternative models for MDMs based on motif co-occurrences and temporal ordering among motifs across multiple dimensions, with detailed formulation of the concepts proposed. The proposed method uses an efficient hashing based record to enable speedy update and retrieval of motif sets, and identification of MDMs. Performance evaluation using synthetic and real body sensor data in unsupervised motif discovery tasks shows that the approach is effective for (a) concurrent processing of multidimensional time series information suitable for real-time applications, (b) finding unknown naturally occurring patterns with minimal delay, and

  2. The distribution of RNA motifs in natural sequences.

    PubMed

    Bourdeau, V; Ferbeyre, G; Pageau, M; Paquin, B; Cedergren, R

    1999-11-15

    Functional analysis of genome sequences has largely ignored RNA genes and their structures. We introduce here the notion of 'ribonomics' to describe the search for the distribution of and eventually the determination of the physiological roles of these RNA structures found in the sequence databases. The utility of this approach is illustrated here by the identification in the GenBank database of RNA motifs having known binding or chemical activity. The frequency of these motifs indicates that most have originated from evolutionary drift and are selectively neutral. On the other hand, their distribution among species and their location within genes suggest that the destiny of these motifs may be more elaborate. For example, the hammerhead motif has a skewed organismal presence, is phylogenetically stable and recent work on a schistosome version confirms its in vivo biological activity. The under-representation of the valine-binding motif and the Rev-binding element in GenBank hints at a detrimental effect on cell growth or viability. Data on the presence and the location of these motifs may provide critical guidance in the design of experiments directed towards the understanding and the manipulation of RNA complexes and activities in vivo.

  3. cWINNOWER Algorithm for Finding Fuzzy DNA Motifs

    NASA Technical Reports Server (NTRS)

    Liang, Shoudan

    2003-01-01

    The cWINNOWER algorithm detects fuzzy motifs in DNA sequences rich in protein-binding signals. A signal is defined as any short nucleotide pattern having up to d mutations differing from a motif of length l. The algorithm finds such motifs if multiple mutated copies of the motif (i.e., the signals) are present in the DNA sequence in sufficient abundance. The cWINNOWER algorithm substantially improves the sensitivity of the winnower method of Pevzner and Sze by imposing a consensus constraint, enabling it to detect much weaker signals. We studied the minimum number of detectable motifs qc as a function of sequence length N for random sequences. We found that qc increases linearly with N for a fast version of the algorithm based on counting three-member sub-cliques. Imposing consensus constraints reduces qc, by a factor of three in this case, which makes the algorithm dramatically more sensitive. Our most sensitive algorithm, which counts four-member sub-cliques, needs a minimum of only 13 signals to detect motifs in a sequence of length N = 12000 for (l,d) = (15,4).

  4. Transcriptional Network Growing Models Using Motif-Based Preferential Attachment.

    PubMed

    Abdelzaher, Ahmed F; Al-Musawi, Ahmad F; Ghosh, Preetam; Mayo, Michael L; Perkins, Edward J

    2015-01-01

    Understanding relationships between architectural properties of gene-regulatory networks (GRNs) has been one of the major goals in systems biology and bioinformatics, as it can provide insights into, e.g., disease dynamics and drug development. Such GRNs are characterized by their scale-free degree distributions and existence of network motifs - i.e., small-node subgraphs that occur more abundantly in GRNs than expected from chance alone. Because these transcriptional modules represent "building blocks" of complex networks and exhibit a wide range of functional and dynamical properties, they may contribute to the remarkable robustness and dynamical stability associated with the whole of GRNs. Here, we developed network-construction models to better understand this relationship, which produce randomized GRNs by using transcriptional motifs as the fundamental growth unit in contrast to other methods that construct similar networks on a node-by-node basis. Because this model produces networks with a prescribed lower bound on the number of choice transcriptional motifs (e.g., downlinks, feed-forward loops), its fidelity to the motif distributions observed in model organisms represents an improvement over existing methods, which we validated by contrasting their resultant motif and degree distributions against existing network-growth models and data from the model organism of the bacterium Escherichia coli. These models may therefore serve as novel testbeds for further elucidating relationships between the topology of transcriptional motifs and network-wide dynamical properties.

  5. Specific regulatory motifs predict glucocorticoid responsiveness of hippocampal gene expression.

    PubMed

    Datson, N A; Polman, J A E; de Jonge, R T; van Boheemen, P T M; van Maanen, E M T; Welten, J; McEwen, B S; Meiland, H C; Meijer, O C

    2011-10-01

    The glucocorticoid receptor (GR) is an ubiquitously expressed ligand-activated transcription factor that mediates effects of cortisol in relation to adaptation to stress. In the brain, GR affects the hippocampus to modulate memory processes through direct binding to glucocorticoid response elements (GREs) in the DNA. However, its effects are to a high degree cell specific, and its target genes in different cell types as well as the mechanisms conferring this specificity are largely unknown. To gain insight in hippocampal GR signaling, we characterized to which GRE GR binds in the rat hippocampus. Using a position-specific scoring matrix, we identified evolutionary-conserved putative GREs from a microarray based set of hippocampal target genes. Using chromatin immunoprecipitation, we were able to confirm GR binding to 15 out of a selection of 32 predicted sites (47%). The majority of these 15 GREs are previously undescribed and thus represent novel GREs that bind GR and therefore may be functional in the rat hippocampus. GRE nucleotide composition was not predictive for binding of GR to a GRE. A search for conserved flanking sequences that may predict GR-GRE interaction resulted in the identification of GC-box associated motifs, such as Myc-associated zinc finger protein 1, within 2 kb of GREs with GR binding in the hippocampus. This enrichment was not present around nonbinding GRE sequences nor around proven GR-binding sites from a mesenchymal stem-like cell dataset that we analyzed. GC-binding transcription factors therefore may be unique partners for DNA-bound GR and may in part explain cell-specific transcriptional regulation by glucocorticoids in the context of the hippocampus.

  6. Mechanisms of Zero-Lag Synchronization in Cortical Motifs

    PubMed Central

    Gollo, Leonardo L.; Mirasso, Claudio; Sporns, Olaf; Breakspear, Michael

    2014-01-01

    Zero-lag synchronization between distant cortical areas has been observed in a diversity of experimental data sets and between many different regions of the brain. Several computational mechanisms have been proposed to account for such isochronous synchronization in the presence of long conduction delays: Of these, the phenomenon of “dynamical relaying” – a mechanism that relies on a specific network motif – has proven to be the most robust with respect to parameter mismatch and system noise. Surprisingly, despite a contrary belief in the community, the common driving motif is an unreliable means of establishing zero-lag synchrony. Although dynamical relaying has been validated in empirical and computational studies, the deeper dynamical mechanisms and comparison to dynamics on other motifs is lacking. By systematically comparing synchronization on a variety of small motifs, we establish that the presence of a single reciprocally connected pair – a “resonance pair” – plays a crucial role in disambiguating those motifs that foster zero-lag synchrony in the presence of conduction delays (such as dynamical relaying) from those that do not (such as the common driving triad). Remarkably, minor structural changes to the common driving motif that incorporate a reciprocal pair recover robust zero-lag synchrony. The findings are observed in computational models of spiking neurons, populations of spiking neurons and neural mass models, and arise whether the oscillatory systems are periodic, chaotic, noise-free or driven by stochastic inputs. The influence of the resonance pair is also robust to parameter mismatch and asymmetrical time delays amongst the elements of the motif. We call this manner of facilitating zero-lag synchrony resonance-induced synchronization, outline the conditions for its occurrence, and propose that it may be a general mechanism to promote zero-lag synchrony in the brain. PMID:24763382

  7. NetMODE: Network Motif Detection without Nauty

    PubMed Central

    Wang, Haidong; Deng, Hualiang; Liu, Xiaoguang; Wang, Gang

    2012-01-01

    A motif in a network is a connected graph that occurs significantly more frequently as an induced subgraph than would be expected in a similar randomized network. By virtue of being atypical, it is thought that motifs might play a more important role than arbitrary subgraphs. Recently, a flurry of advances in the study of network motifs has created demand for faster computational means for identifying motifs in increasingly larger networks. Motif detection is typically performed by enumerating subgraphs in an input network and in an ensemble of comparison networks; this poses a significant computational problem. Classifying the subgraphs encountered, for instance, is typically performed using a graph canonical labeling package, such as Nauty, and will typically be called billions of times. In this article, we describe an implementation of a network motif detection package, which we call NetMODE. NetMODE can only perform motif detection for -node subgraphs when , but does so without the use of Nauty. To avoid using Nauty, NetMODE has an initial pretreatment phase, where -node graph data is stored in memory (). For we take a novel approach, which relates to the Reconstruction Conjecture for directed graphs. We find that NetMODE can perform up to around times faster than its predecessors when and up to around times faster when (the exact improvement varies considerably). NetMODE also (a) includes a method for generating comparison graphs uniformly at random, (b) can interface with external packages (e.g. R), and (c) can utilize multi-core architectures. NetMODE is available from netmode.sf.net. PMID:23272055

  8. Construction of validated, non-redundant composite protein sequence databases.

    PubMed

    Bleasby, A J; Wootton, J C

    1990-01-01

    A strategy has been developed for the construction of a validated, comprehensive composite protein sequence database. Entries are amalgamated from primary source data bases by a largely automated set of processes in which redundant and trivially different entries are eliminated. A modular approach has been adopted to allow scientific judgement to be used at each stage of database processing and amalgamation. Source databases are assigned a priority depending on the quality of sequence validation and commenting. Rejection of entries from the lower priority database, in each pairwise comparison of databases, is carried out according to optionally defined redundancy criteria based on sequence segment mismatches. Efficient algorithms for this methodology are embodied in the COMPO software system. COMPO has been applied for over 2 years in construction and regular updating of the OWL composite protein sequence database from the source databases NBRF-PIR, SWISS-PROT, a GenBank translation retrieved from the feature tables, NBRF-NEW, NEWAT86, PSD-KYOTO and the sequences contained in the Brookhaven protein structure databank. OWL is part of the ISIS integrated data resource of protein sequence and structure [Akrigg et al. (1988) Nature, 335, 745-746]. The modular nature of the integration process greatly facilitates the frequent updating of OWL following releases of the source databases. The extent of redundancy in these sources is revealed by the comparison process. The advantages of a robust composite database for sequence similarity searching and information retrieval are discussed.

  9. IQ-motif peptides as novel anti-microbial agents.

    PubMed

    McLean, Denise T F; Lundy, Fionnuala T; Timson, David J

    2013-04-01

    The IQ-motif is an amphipathic, often positively charged, α-helical, calmodulin binding sequence found in a number of eukaryote signalling, transport and cytoskeletal proteins. They share common biophysical characteristics with established, cationic α-helical antimicrobial peptides, such as the human cathelicidin LL-37. Therefore, we tested eight peptides encoding the sequences of IQ-motifs derived from the human cytoskeletal scaffolding proteins IQGAP2 and IQGAP3. Some of these peptides were able to inhibit the growth of Escherichia coli and Staphylococcus aureus with minimal inhibitory concentrations (MIC) comparable to LL-37. In addition some IQ-motifs had activity against the fungus Candida albicans. This antimicrobial activity is combined with low haemolytic activity (comparable to, or lower than, that of LL-37). Those IQ-motifs with anti-microbial activity tended to be able to bind to lipopolysaccharide. Some of these were also able to permeabilise the cell membranes of both Gram positive and Gram negative bacteria. These results demonstrate that IQ-motifs are viable lead sequences for the identification and optimisation of novel anti-microbial peptides. Thus, further investigation of the anti-microbial properties of this diverse group of sequences is merited.

  10. Interconnected Network Motifs Control Podocyte Morphology and Kidney Function

    PubMed Central

    Azeloglu, Evren U.; Hardy, Simon V.; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y.; Fang, Wei; Xiong, Huabao; Neves, Susana R.; Jain, Mohit R.; Li, Hong; Ma’ayan, Avi; Gordon, Ronald E.; He, John Cijiang; Iyengar, Ravi

    2014-01-01

    Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3′,5′-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element–binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor–driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease. PMID:24497609

  11. cWINNOWER algorithm for finding fuzzy dna motifs

    NASA Technical Reports Server (NTRS)

    Liang, S.; Samanta, M. P.; Biegel, B. A.

    2004-01-01

    The cWINNOWER algorithm detects fuzzy motifs in DNA sequences rich in protein-binding signals. A signal is defined as any short nucleotide pattern having up to d mutations differing from a motif of length l. The algorithm finds such motifs if a clique consisting of a sufficiently large number of mutated copies of the motif (i.e., the signals) is present in the DNA sequence. The cWINNOWER algorithm substantially improves the sensitivity of the winnower method of Pevzner and Sze by imposing a consensus constraint, enabling it to detect much weaker signals. We studied the minimum detectable clique size qc as a function of sequence length N for random sequences. We found that qc increases linearly with N for a fast version of the algorithm based on counting three-member sub-cliques. Imposing consensus constraints reduces qc by a factor of three in this case, which makes the algorithm dramatically more sensitive. Our most sensitive algorithm, which counts four-member sub-cliques, needs a minimum of only 13 signals to detect motifs in a sequence of length N = 12,000 for (l, d) = (15, 4). Copyright Imperial College Press.

  12. Fitting a mixture model by expectation maximization to discover motifs in biopolymers

    SciTech Connect

    Bailey, T.L.; Elkan, C.

    1994-12-31

    The algorithm described in this paper discovers one or more motifs in a collection of DNA or protein sequences by using the technique of expectation maximization to fit a two-component finite mixture model to the set of sequences. Multiple motifs are found by fitting a mixture model to the data, probabilistically erasing the occurrences of the motif thus found, and repeating the process to find successive motifs. The algorithm requires only a set of unaligned sequences and a number specifying the width of the motifs as input. It returns a model of each motif and a threshold which together can be used as a Bayes-optimal classifier for searching for occurrences of the motif in other databases. The algorithm estimates how many times each motif occurs in each sequence in the dataset and outputs an alignment of the occurrences of the motif. The algorithm is capable of discovering several different motifs with differing numbers of occurrences in a single dataset.

  13. Novel Structural and Functional Motifs in cellulose synthase (CesA) Genes of Bread Wheat (Triticum aestivum, L.)

    PubMed Central

    Kaur, Simerjeet; Dhugga, Kanwarpal S.; Gill, Kulvinder; Singh, Jaswinder

    2016-01-01

    Cellulose is the primary determinant of mechanical strength in plant tissues. Late-season lodging is inversely related to the amount of cellulose in a unit length of the stem. Wheat is the most widely grown of all the crops globally, yet information on its CesA gene family is limited. We have identified 22 CesA genes from bread wheat, which include homoeologs from each of the three genomes, and named them as TaCesAXA, TaCesAXB or TaCesAXD, where X denotes the gene number and the last suffix stands for the respective genome. Sequence analyses of the CESA proteins from wheat and their orthologs from barley, maize, rice, and several dicot species (Arabidopsis, beet, cotton, poplar, potato, rose gum and soybean) revealed motifs unique to monocots (Poales) or dicots. Novel structural motifs CQIC and SVICEXWFA were identified, which distinguished the CESAs involved in the formation of primary and secondary cell wall (PCW and SCW) in all the species. We also identified several new motifs specific to monocots or dicots. The conserved motifs identified in this study possibly play functional roles specific to PCW or SCW formation. The new insights from this study advance our knowledge about the structure, function and evolution of the CesA family in plants in general and wheat in particular. This information will be useful in improving culm strength to reduce lodging or alter wall composition to improve biofuel production. PMID:26771740

  14. Novel Structural and Functional Motifs in cellulose synthase (CesA) Genes of Bread Wheat (Triticum aestivum, L.).

    PubMed

    Kaur, Simerjeet; Dhugga, Kanwarpal S; Gill, Kulvinder; Singh, Jaswinder

    2016-01-01

    Cellulose is the primary determinant of mechanical strength in plant tissues. Late-season lodging is inversely related to the amount of cellulose in a unit length of the stem. Wheat is the most widely grown of all the crops globally, yet information on its CesA gene family is limited. We have identified 22 CesA genes from bread wheat, which include homoeologs from each of the three genomes, and named them as TaCesAXA, TaCesAXB or TaCesAXD, where X denotes the gene number and the last suffix stands for the respective genome. Sequence analyses of the CESA proteins from wheat and their orthologs from barley, maize, rice, and several dicot species (Arabidopsis, beet, cotton, poplar, potato, rose gum and soybean) revealed motifs unique to monocots (Poales) or dicots. Novel structural motifs CQIC and SVICEXWFA were identified, which distinguished the CESAs involved in the formation of primary and secondary cell wall (PCW and SCW) in all the species. We also identified several new motifs specific to monocots or dicots. The conserved motifs identified in this study possibly play functional roles specific to PCW or SCW formation. The new insights from this study advance our knowledge about the structure, function and evolution of the CesA family in plants in general and wheat in particular. This information will be useful in improving culm strength to reduce lodging or alter wall composition to improve biofuel production.

  15. Selection against spurious promoter motifs correlates withtranslational efficiency across bacteria

    SciTech Connect

    Froula, Jeffrey L.; Francino, M. Pilar

    2007-05-01

    Because binding of RNAP to misplaced sites could compromise the efficiency of transcription, natural selection for the optimization of gene expression should regulate the distribution of DNA motifs capable of RNAP-binding across the genome. Here we analyze the distribution of the -10 promoter motifs that bind the {sigma}{sup 70} subunit of RNAP in 42 bacterial genomes. We show that selection on these motifs operates across the genome, maintaining an over-representation of -10 motifs in regulatory sequences while eliminating them from the nonfunctional and, in most cases, from the protein coding regions. In some genomes, however, -10 sites are over-represented in the coding sequences; these sites could induce pauses effecting regulatory roles throughout the length of a transcriptional unit. For nonfunctional sequences, the extent of motif under-representation varies across genomes in a manner that broadly correlates with the number of tRNA genes, a good indicator of translational speed and growth rate. This suggests that minimizing the time invested in gene transcription is an important selective pressure against spurious binding. However, selection against spurious binding is detectable in the reduced genomes of host-restricted bacteria that grow at slow rates, indicating that components of efficiency other than speed may also be important. Minimizing the number of RNAP molecules per cell required for transcription, and the corresponding energetic expense, may be most relevant in slow growers. These results indicate that genome-level properties affecting the efficiency of transcription and translation can respond in an integrated manner to optimize gene expression. The detection of selection against promoter motifs in nonfunctional regions also implies that no sequence may evolve free of selective constraints, at least in the relatively small and unstructured genomes of bacteria.

  16. [Specific motifs in the genomes of the family Chlamydiaceae].

    PubMed

    Demkin, V V; Kirillova, N V

    2012-01-01

    Specific motifs in the genomes of the family Chlamydiaceae were discussed. The search for genetic markers ofbacteria identification and typing is an urgent problem. The progress in sequencing technology resulted in compilation of the database of genomic nucleotide sequences of bacteria. This raised the problem of the search and selection of genetic targets for identification and typing in bacterial genes based on comparative analysis of complete genomic sequences. The goal of this work was to implement comparative genetic analysis of different species of the family Chlamydiaceae. This analysis was focused to detection of specific motifs capable of serving as genetic marker of this family. The consensus domains were detected using the Visual Basic for Application software for MS Excel. Complete coincidence of segments 25 nucleotide long was used as the test for consensus domain selection. One complete genomic sequence for each of 8 bacterial species was taken for the experiment. The experimental sample did not contain complete sequence of C. suis, because at the moment of this research this species was absence in the database GenBank. Comparative assay of the sequences of the C. trachomatis and other representatives of the family Chlamydiaceae revealed 41 common motifs for 8 Chlamydiaceae species tested in this work. The maximal number of consensus motifs was observed in genes of ribosomal RNA and t-RNA. In addition to genes of r-RNA and t-RNA consensus motifs were observed in 5 genes and 6 intergene segments. The gene CTL0299, CTLO800, dagA, and hctA consensus motifs detected in this work can be regarded as identification domains of the family Chlamydiaceae.

  17. Specific RNA self-assembly with minimal paranemic motifs.

    PubMed

    Afonin, Kirill A; Cieply, Dennis J; Leontis, Neocles B

    2008-01-09

    The paranemic crossover (PX) is a motif for assembling two nucleic acid molecules using Watson-Crick (WC) basepairing without unfolding preformed secondary structure in the individual molecules. Once formed, the paranemic assembly motif comprises adjacent parallel double helices that crossover at every possible point over the length of the motif. The interaction is reversible as it does not require denaturation of basepairs internal to each interacting molecular unit. Paranemic assembly has been demonstrated for DNA but not for RNA and only for motifs with four or more crossover points and lengths of five or more helical half-turns. Here we report the design of RNA molecules that paranemically assemble with the minimum number of two crossovers spanning the major groove to form paranemic motifs with a length of three half turns (3HT). Dissociation constants (Kd's) were measured for a series of molecules in which the number of basepairs between the crossover points was varied from five to eight basepairs. The paranemic 3HT complex with six basepairs (3HT_6M) was found to be the most stable with Kd = 1 x 10-8 M. The half-time for kinetic exchange of the 3HT_6M complex was determined to be approximately 100 min, from which we calculated association and dissociation rate constants ka = 5.11 x 103 M-1s-1 and kd = 5.11 x 10-5 s-1. RNA paranemic assembly of 3HT and 5HT complexes is blocked by single-base substitutions that disrupt individual intermolecular Watson-Crick basepairs and is restored by compensatory substitutions that restore those basepairs. The 3HT motif appears suitable for specific, programmable, and reversible tecto-RNA self-assembly for constructing artificial RNA molecular machines.

  18. Characterizing regulatory path motifs in integrated networks using perturbational data

    PubMed Central

    2010-01-01

    We introduce Pathicular http://bioinformatics.psb.ugent.be/software/details/Pathicular, a Cytoscape plugin for studying the cellular response to perturbations of transcription factors by integrating perturbational expression data with transcriptional, protein-protein and phosphorylation networks. Pathicular searches for 'regulatory path motifs', short paths in the integrated physical networks which occur significantly more often than expected between transcription factors and their targets in the perturbational data. A case study in Saccharomyces cerevisiae identifies eight regulatory path motifs and demonstrates their biological significance. PMID:20230615

  19. A Command Editor Tool for X and Motif

    DTIC Science & Technology

    1993-07-01

    1of 16 h.. . . .. .. . . . . . .I .... . . . .. . . . . . . .- I m arble X/Motlf Design Document for Contract # DAAH01-93-C-R013 minimal implementation...Motif 2 of 18 m arble X/Motif Design Document for Contract # DAAH01-93-C-R013 ing of modified system widgets, proides to the developer the full source...oa’rutmz ol"croidctv fteseilmd h A iandEio olfrX n oi f1 i~lol’lot m arble Xfflotlf De*ign Documnent for Contract # DAAHOI-93-C-R013 user has just

  20. Nephila clavipes Flagelliform Silk-like GGX Motifs Contribute to Extensibility and Spacer Motifs Contribute to Strength in Synthetic Spider Silk Fibers

    PubMed Central

    Adrianos, Sherry L.; Teulé, Florence; Hinman, Michael B.; Jones, Justin A.; Weber, Warner S.; Yarger, Jeffery L.; Lewis, Randolph V.

    2013-01-01

    Flagelliform spider silk is the most extensible silk fiber produced by orb weaver spiders, though not as strong as the dragline silk of the spider. The motifs found in the core of the Nephila clavipes flagelliform Flag protein are: GGX, spacer, and GPGGX. Flag does not contain the polyalanine motif known to provide the strength of dragline silk. To investigate the source of flagelliform fiber strength, four recombinant proteins were produced containing variations of the three core motifs of the Nephila clavipes flagelliform Flag protein that produces this type of fiber. The as-spun fibers were processed in 80% aqueous isopropanol using a standardized process for all four fiber types, which produced improved mechanical properties. Mechanical testing of the recombinant proteins determined that the GGX motif contributes extensibility and the spacer motif contributes strength to the recombinant fibers. Recombinant protein fibers containing the spacer motif were stronger than the proteins constructed without the spacer that contained only the GGX motif or the combination of the GGX and GPGGX motifs. The mechanical and structural X-ray diffraction analysis of the recombinant fibers provide data that suggests a functional role of the spacer motif that produces tensile strength though the spacer motif is not clearly defined structurally. These results indicate that the spacer is likely a primary contributor of strength with the GGX motif supplying mobility to the protein network of native N. clavipes flagelliform silk fibers. PMID:23646825

  1. Nephila clavipes Flagelliform silk-like GGX motifs contribute to extensibility and spacer motifs contribute to strength in synthetic spider silk fibers.

    PubMed

    Adrianos, Sherry L; Teulé, Florence; Hinman, Michael B; Jones, Justin A; Weber, Warner S; Yarger, Jeffery L; Lewis, Randolph V

    2013-06-10

    Flagelliform spider silk is the most extensible silk fiber produced by orb weaver spiders, though not as strong as the dragline silk of the spider. The motifs found in the core of the Nephila clavipes flagelliform Flag protein are GGX, spacer, and GPGGX. Flag does not contain the polyalanine motif known to provide the strength of dragline silk. To investigate the source of flagelliform fiber strength, four recombinant proteins were produced containing variations of the three core motifs of the Nephila clavipes flagelliform Flag protein that produces this type of fiber. The as-spun fibers were processed in 80% aqueous isopropanol using a standardized process for all four fiber types, which produced improved mechanical properties. Mechanical testing of the recombinant proteins determined that the GGX motif contributes extensibility and the spacer motif contributes strength to the recombinant fibers. Recombinant protein fibers containing the spacer motif were stronger than the proteins constructed without the spacer that contained only the GGX motif or the combination of the GGX and GPGGX motifs. The mechanical and structural X-ray diffraction analysis of the recombinant fibers provide data that suggests a functional role of the spacer motif that produces tensile strength, though the spacer motif is not clearly defined structurally. These results indicate that the spacer is likely a primary contributor of strength, with the GGX motif supplying mobility to the protein network of native N. clavipes flagelliform silk fibers.

  2. Core signalling motif displaying multistability through multi-state enzymes

    PubMed Central

    Feng, Song; Sáez, Meritxell; Wiuf, Carsten; Feliu, Elisenda

    2016-01-01

    Bistability, and more generally multistability, is a key system dynamics feature enabling decision-making and memory in cells. Deciphering the molecular determinants of multistability is thus crucial for a better understanding of cellular pathways and their (re)engineering in synthetic biology. Here, we show that a key motif found predominantly in eukaryotic signalling systems, namely a futile signalling cycle, can display bistability when featuring a two-state kinase. We provide necessary and sufficient mathematical conditions on the kinetic parameters of this motif that guarantee the existence of multiple steady states. These conditions foster the intuition that bistability arises as a consequence of competition between the two states of the kinase. Extending from this result, we find that increasing the number of kinase states linearly translates into an increase in the number of steady states in the system. These findings reveal, to our knowledge, a new mechanism for the generation of bistability and multistability in cellular signalling systems. Further the futile cycle featuring a two-state kinase is among the smallest bistable signalling motifs. We show that multi-state kinases and the described competition-based motif are part of several natural signalling systems and thereby could enable them to implement complex information processing through multistability. These results indicate that multi-state kinases in signalling systems are readily exploited by natural evolution and could equally be used by synthetic approaches for the generation of multistable information processing systems at the cellular level. PMID:27733693

  3. Conditional graphical models for protein structural motif recognition.

    PubMed

    Liu, Yan; Carbonell, Jaime; Gopalakrishnan, Vanathi; Weigele, Peter

    2009-05-01

    Determining protein structures is crucial to understanding the mechanisms of infection and designing drugs. However, the elucidation of protein folds by crystallographic experiments can be a bottleneck in the development process. In this article, we present a probabilistic graphical model framework, conditional graphical models, for predicting protein structural motifs. It represents the structure characteristics of a structural motif using a graph, where the nodes denote the secondary structure elements, and the edges indicate the side-chain interactions between the components either within one protein chain or between chains. Then the model defines the optimal segmentation of a protein sequence against the graph by maximizing its "conditional" probability so that it can take advantages of the discriminative training approach. Efficient approximate inference algorithms using reversible jump Markov Chain Monte Carlo (MCMC) algorithm are developed to handle the resulting complex graphical models. We test our algorithm on four important structural motifs, and our method outperforms other state-of-art algorithms for motif recognition. We also hypothesize potential membership proteins of target folds from Swiss-Prot, which further supports the evolutionary hypothesis about viral folds.

  4. Motifs in triadic random graphs based on Steiner triple systems

    NASA Astrophysics Data System (ADS)

    Winkler, Marco; Reichardt, Jörg

    2013-08-01

    Conventionally, pairwise relationships between nodes are considered to be the fundamental building blocks of complex networks. However, over the last decade, the overabundance of certain subnetwork patterns, i.e., the so-called motifs, has attracted much attention. It has been hypothesized that these motifs, instead of links, serve as the building blocks of network structures. Although the relation between a network's topology and the general properties of the system, such as its function, its robustness against perturbations, or its efficiency in spreading information, is the central theme of network science, there is still a lack of sound generative models needed for testing the functional role of subgraph motifs. Our work aims to overcome this limitation. We employ the framework of exponential random graph models (ERGMs) to define models based on triadic substructures. The fact that only a small portion of triads can actually be set independently poses a challenge for the formulation of such models. To overcome this obstacle, we use Steiner triple systems (STSs). These are partitions of sets of nodes into pair-disjoint triads, which thus can be specified independently. Combining the concepts of ERGMs and STSs, we suggest generative models capable of generating ensembles of networks with nontrivial triadic Z-score profiles. Further, we discover inevitable correlations between the abundance of triad patterns, which occur solely for statistical reasons and need to be taken into account when discussing the functional implications of motif statistics. Moreover, we calculate the degree distributions of our triadic random graphs analytically.

  5. Forward and Back: Motifs of Inhibition in Olfactory Processing

    PubMed Central

    Bazhenov, Maxim; Stopfer, Mark

    2016-01-01

    The remarkable performance of the olfactory system in classifying and categorizing the complex olfactory environment is built upon several basic neural circuit motifs. These include forms of inhibition that may play comparable roles in widely divergent species. In this issue of Neuron, a new study by Stokes and Isaacson sheds light on how elementary types of inhibition dynamically interact. PMID:20696373

  6. Insights into the motif preference of APOBEC3 enzymes.

    PubMed

    Ebrahimi, Diako; Alinejad-Rokny, Hamid; Davenport, Miles P

    2014-01-01

    We used a multivariate data analysis approach to identify motifs associated with HIV hypermutation by different APOBEC3 enzymes. The analysis showed that APOBEC3G targets G mainly within GG, TG, TGG, GGG, TGGG and also GGGT. The G nucleotides flanked by a C at the 3' end (in +1 and +2 positions) were indicated as disfavoured targets by APOBEC3G. The G nucleotides within GGGG were found to be targeted at a frequency much less than what is expected. We found that the infrequent G-to-A mutation within GGGG is not limited to the inaccessibility, to APOBEC3, of poly Gs in the central and 3'polypurine tracts (PPTs) which remain double stranded during the HIV reverse transcription. GGGG motifs outside the PPTs were also disfavoured. The motifs GGAG and GAGG were also found to be disfavoured targets for APOBEC3. The motif-dependent mutation of G within the HIV genome by members of the APOBEC3 family other than APOBEC3G was limited to GA→AA changes. The results did not show evidence of other types of context dependent G-to-A changes in the HIV genome.

  7. Insights into the Motif Preference of APOBEC3 Enzymes

    PubMed Central

    Ebrahimi, Diako; Alinejad-Rokny, Hamid; Davenport, Miles P.

    2014-01-01

    We used a multivariate data analysis approach to identify motifs associated with HIV hypermutation by different APOBEC3 enzymes. The analysis showed that APOBEC3G targets G mainly within GG, TG, TGG, GGG, TGGG and also GGGT. The G nucleotides flanked by a C at the 3′ end (in +1 and +2 positions) were indicated as disfavoured targets by APOBEC3G. The G nucleotides within GGGG were found to be targeted at a frequency much less than what is expected. We found that the infrequent G-to-A mutation within GGGG is not limited to the inaccessibility, to APOBEC3, of poly Gs in the central and 3′polypurine tracts (PPTs) which remain double stranded during the HIV reverse transcription. GGGG motifs outside the PPTs were also disfavoured. The motifs GGAG and GAGG were also found to be disfavoured targets for APOBEC3. The motif-dependent mutation of G within the HIV genome by members of the APOBEC3 family other than APOBEC3G was limited to GA→AA changes. The results did not show evidence of other types of context dependent G-to-A changes in the HIV genome. PMID:24498164

  8. 5. DETAIL VIEW OF THE EGYPTIAN MOTIF DECORATIVE ELEMENTS OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. DETAIL VIEW OF THE EGYPTIAN MOTIF DECORATIVE ELEMENTS OF BUILDING 1'S MAIN ENTRY TOWER (INCLUDING THE ENGAGED COLUMN CAPITALS, PILASTERS & CAPITALS, CORNICES, AND TERRA COTTA EAGLES); LOOKING SW FROM THE E WING ROOF. (Ryan) - Veterans Administration Medical Center, Building No. 1, Old State Route 13 West, Marion, Williamson County, IL

  9. DNA containing CpG motifs induces angiogenesis

    NASA Astrophysics Data System (ADS)

    Zheng, Mei; Klinman, Dennis M.; Gierynska, Malgorzata; Rouse, Barry T.

    2002-06-01

    New blood vessel formation in the cornea is an essential step in the pathogenesis of a blinding immunoinflammatory reaction caused by ocular infection with herpes simplex virus (HSV). By using a murine corneal micropocket assay, we found that HSV DNA (which contains a significant excess of potentially bioactive "CpG" motifs when compared with mammalian DNA) induces angiogenesis. Moreover, synthetic oligodeoxynucleotides containing CpG motifs attract inflammatory cells and stimulate the release of vascular endothelial growth factor (VEGF), which in turn triggers new blood vessel formation. In vitro, CpG DNA induces the J774A.1 murine macrophage cell line to produce VEGF. In vivo CpG-induced angiogenesis was blocked by the administration of anti-mVEGF Ab or the inclusion of "neutralizing" oligodeoxynucleotides that specifically oppose the stimulatory activity of CpG DNA. These findings establish that DNA containing bioactive CpG motifs induces angiogenesis, and suggest that CpG motifs in HSV DNA may contribute to the blinding lesions of stromal keratitis.

  10. Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells.

    PubMed

    Hutchins, Andrew Paul; Choo, Siew Hua; Mistri, Tapan Kumar; Rahmani, Mehran; Woon, Chow Thai; Ng, Calista Keow Leng; Jauch, Ralf; Robson, Paul

    2013-02-01

    Transcription factors (TF) often bind in heterodimeric complexes with each TF recognizing a specific neighboring cis element in the regulatory region of the genome. Comprehension of this DNA motif grammar is opaque, yet recent developments have allowed the interrogation of genome-wide TF binding sites. We reasoned that within this data novel motif grammars could be identified that controlled distinct biological programs. For this purpose, we developed a novel motif-discovery tool termed fexcom that systematically interrogates ChIP-seq data to discover spatially constrained TF-TF composite motifs occurring over short DNA distances. We applied this to the extensive ChIP-seq data available from mouse embryonic stem cells (ESCs). In addition to the well-known and most prevalent sox-oct motif, we also discovered a novel constrained spacer motif for Esrrb and Sox2 with a gap of between 2 and 8 bps that Essrb and Sox2 cobind in a selective fashion. Through the use of knockdown experiments, we argue that the Esrrb-Sox2 complex is an arbiter of gene expression differences between ESCs and epiblast stem cells (EpiSC). A number of genes downregulated upon dual Esrrb/Sox2 knockdown (e.g., Klf4, Klf5, Jam2, Pecam1) are similarly downregulated in the ESC to EpiSC transition and contain the esrrb-sox motif. The prototypical Esrrb-Sox2 target gene, containing an esrrb-sox element conserved throughout eutherian and metatherian mammals, is Nr0b1. Through positive regulation of this transcriptional repressor, we argue the Esrrb-Sox2 complex promotes the ESC state through inhibition of the EpiSC transcriptional program and the same trio may also function to maintain trophoblast stem cells.

  11. Motivated Proteins: A web application for studying small three-dimensional protein motifs

    PubMed Central

    Leader, David P; Milner-White, E James

    2009-01-01

    Background Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are αβ-motifs, asx-motifs, asx-turns, β-bulges, β-bulge loops, β-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns. We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. Description The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. Conclusion Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schema. PMID:19210785

  12. An Integrated Procedure for the Structural Design of a Composite Rotor-Hydrofoil of a Water Current Turbine (WCT)

    NASA Astrophysics Data System (ADS)

    Oller Aramayo, S. A.; Nallim, L. G.; Oller, S.

    2013-12-01

    This paper shows an integrated structural design optimization of a composite rotor-hydrofoil of a water current turbine by means the finite elements method (FEM), using a Serial/Parallel mixing theory (Rastellini et al. Comput. Struct. 86:879-896, 2008, Martinez et al., 2007, Martinez and Oller Arch. Comput. Methods. 16(4):357-397, 2009, Martinez et al. Compos. Part B Eng. 42(2011):134-144, 2010) coupled with a fluid-dynamic formulation and multi-objective optimization algorithm (Gen and Cheng 1997, Lee et al. Compos. Struct. 99:181-192, 2013, Lee et al. Compos. Struct. 94(3):1087-1096, 2012). The composite hydrofoil of the turbine rotor has been design using a reinforced laminate composites, taking into account the optimization of the carbon fiber orientation to obtain the maximum strength and lower rotational-inertia. Also, these results have been compared with a steel hydrofoil remarking the different performance on both structures. The mechanical and geometrical parameters involved in the design of this fiber-reinforced composite material are the fiber orientation, number of layers, stacking sequence and laminate thickness. Water pressure in the rotor of the turbine is obtained from a coupled fluid-dynamic simulation (CFD), whose detail can be found in the reference Oller et al. (2012). The main purpose of this paper is to achieve a very low inertia rotor minimizing the start-stop effect, because it is applied in axial water flow turbine currently in design by the authors, in which is important to take the maximum advantage of the kinetic energy. The FEM simulation codes are engineered by CIMNE (International Center for Numerical Method in Engineering, Barcelona, Spain), COMPack for the solids problem application, KRATOS for fluid dynamic application and RMOP for the structural optimization. To validate the procedure here presented, many turbine rotors made of composite materials are analyzed and three of them are compared with the steel one.

  13. A Bioinformatics Approach for Detecting Repetitive Nested Motifs using Pattern Matching

    PubMed Central

    Romero, José R.; Carballido, Jessica A.; Garbus, Ingrid; Echenique, Viviana C.; Ponzoni, Ignacio

    2016-01-01

    The identification of nested motifs in genomic sequences is a complex computational problem. The detection of these patterns is important to allow the discovery of transposable element (TE) insertions, incomplete reverse transcripts, deletions, and/or mutations. In this study, a de novo strategy for detecting patterns that represent nested motifs was designed based on exhaustive searches for pairs of motifs and combinatorial pattern analysis. These patterns can be grouped into three categories, motifs within other motifs, motifs flanked by other motifs, and motifs of large size. The methodology used in this study, applied to genomic sequences from the plant species Aegilops tauschii and Oryza sativa, revealed that it is possible to identify putative nested TEs by detecting these three types of patterns. The results were validated through BLAST alignments, which revealed the efficacy and usefulness of the new method, which is called Mamushka. PMID:27812277

  14. FPGA implementation of motifs-based neuronal network and synchronization analysis

    NASA Astrophysics Data System (ADS)

    Deng, Bin; Zhu, Zechen; Yang, Shuangming; Wei, Xile; Wang, Jiang; Yu, Haitao

    2016-06-01

    Motifs in complex networks play a crucial role in determining the brain functions. In this paper, 13 kinds of motifs are implemented with Field Programmable Gate Array (FPGA) to investigate the relationships between the networks properties and motifs properties. We use discretization method and pipelined architecture to construct various motifs with Hindmarsh-Rose (HR) neuron as the node model. We also build a small-world network based on these motifs and conduct the synchronization analysis of motifs as well as the constructed network. We find that the synchronization properties of motif determine that of motif-based small-world network, which demonstrates effectiveness of our proposed hardware simulation platform. By imitation of some vital nuclei in the brain to generate normal discharges, our proposed FPGA-based artificial neuronal networks have the potential to replace the injured nuclei to complete the brain function in the treatment of Parkinson's disease and epilepsy.

  15. A Bioinformatics Approach for Detecting Repetitive Nested Motifs using Pattern Matching.

    PubMed

    Romero, José R; Carballido, Jessica A; Garbus, Ingrid; Echenique, Viviana C; Ponzoni, Ignacio

    2016-01-01

    The identification of nested motifs in genomic sequences is a complex computational problem. The detection of these patterns is important to allow the discovery of transposable element (TE) insertions, incomplete reverse transcripts, deletions, and/or mutations. In this study, a de novo strategy for detecting patterns that represent nested motifs was designed based on exhaustive searches for pairs of motifs and combinatorial pattern analysis. These patterns can be grouped into three categories, motifs within other motifs, motifs flanked by other motifs, and motifs of large size. The methodology used in this study, applied to genomic sequences from the plant species Aegilops tauschii and Oryza sativa, revealed that it is possible to identify putative nested TEs by detecting these three types of patterns. The results were validated through BLAST alignments, which revealed the efficacy and usefulness of the new method, which is called Mamushka.

  16. WildSpan: mining structured motifs from protein sequences

    PubMed Central

    2011-01-01

    Background Automatic extraction of motifs from biological sequences is an important research problem in study of molecular biology. For proteins, it is desired to discover sequence motifs containing a large number of wildcard symbols, as the residues associated with functional sites are usually largely separated in sequences. Discovering such patterns is time-consuming because abundant combinations exist when long gaps (a gap consists of one or more successive wildcards) are considered. Mining algorithms often employ constraints to narrow down the search space in order to increase efficiency. However, improper constraint models might degrade the sensitivity and specificity of the motifs discovered by computational methods. We previously proposed a new constraint model to handle large wildcard regions for discovering functional motifs of proteins. The patterns that satisfy the proposed constraint model are called W-patterns. A W-pattern is a structured motif that groups motif symbols into pattern blocks interleaved with large irregular gaps. Considering large gaps reflects the fact that functional residues are not always from a single region of protein sequences, and restricting motif symbols into clusters corresponds to the observation that short motifs are frequently present within protein families. To efficiently discover W-patterns for large-scale sequence annotation and function prediction, this paper first formally introduces the problem to solve and proposes an algorithm named WildSpan (sequential pattern mining across large wildcard regions) that incorporates several pruning strategies to largely reduce the mining cost. Results WildSpan is shown to efficiently find W-patterns containing conserved residues that are far separated in sequences. We conducted experiments with two mining strategies, protein-based and family-based mining, to evaluate the usefulness of W-patterns and performance of WildSpan. The protein-based mining mode of WildSpan is developed for

  17. Association of branched oligonucleotides into the i-motif.

    PubMed

    Robidoux, S; Klinck, R; Gehring, K; Damha, M J

    1997-12-01

    The unique architecture of branched oligonucleotides mimicking lariat RNA introns [Wallace and Edmons, Proc. Natl. Acad. Sci. USA 80, 950-954 (1983)] was exploited to study compounds that associate as two parallel duplexes with intercalating C/C+ base pairs (i-motif DNA) [Gehring et al. Nature 363, 561-565 (1993)]. The formation of a branched cytosine tetrad was induced by joining the 5'-ends of pair of pentadeoxycytidine strands with a branching riboadenosine (rA) linker. This arrangement causes the orientation of the dC strands to be parallel, and forces the formation of a C/C+ duplex that self-associates into i-DNA. Presence of the i-motif in this structure is supported by thermal denaturation, native gel electrophoresis, CD, and NMR spectroscopy.

  18. Finding sequence motifs in groups of functionally related proteins.

    PubMed

    Smith, H O; Annau, T M; Chandrasegaran, S

    1990-01-01

    We have developed a method for rapidly finding patterns of conserved amino acid residues (motifs) in groups of functionally related proteins. All 3-amino acid patterns in a group of proteins of the type aa1 d1 aa2 d2 aa3, where d1 and d2 are distances that can be varied in a range up to 24 residues, are accumulated into an array. Segments of the proteins containing those patterns that occur most frequently are aligned on each other by a scoring method that obtains an average relatedness value for all the amino acids in each column of the aligned sequence block based on the Dayhoff relatedness odds matrix. The automated method successfully finds and displays nearly all of the sequence motifs that have been previously reported to occur in 33 reverse transcriptases, 18 DNA integrases, and 30 DNA methyltransferases.

  19. Graph animals, subgraph sampling, and motif search in large networks.

    PubMed

    Baskerville, Kim; Grassberger, Peter; Paczuski, Maya

    2007-09-01

    We generalize a sampling algorithm for lattice animals (connected clusters on a regular lattice) to a Monte Carlo algorithm for "graph animals," i.e., connected subgraphs in arbitrary networks. As with the algorithm in [N. Kashtan et al., Bioinformatics 20, 1746 (2004)], it provides a weighted sample, but the computation of the weights is much faster (linear in the size of subgraphs, instead of superexponential). This allows subgraphs with up to ten or more nodes to be sampled with very high statistics, from arbitrarily large networks. Using this together with a heuristic algorithm for rapidly classifying isomorphic graphs, we present results for two protein interaction networks obtained using the tandem affinity purification (TAP) method: one of Escherichia coli with 230 nodes and 695 links, and one for yeast (Saccharomyces cerevisiae) with roughly ten times more nodes and links. We find in both cases that most connected subgraphs are strong motifs (Z scores >10) or antimotifs (Z scores <-10) when the null model is the ensemble of networks with fixed degree sequence. Strong differences appear between the two networks, with dominant motifs in E. coli being (nearly) bipartite graphs and having many pairs of nodes that connect to the same neighbors, while dominant motifs in yeast tend towards completeness or contain large cliques. We also explore a number of methods that do not rely on measurements of Z scores or comparisons with null models. For instance, we discuss the influence of specific complexes like the 26S proteasome in yeast, where a small number of complexes dominate the k cores with large k and have a decisive effect on the strongest motifs with 6-8 nodes. We also present Zipf plots of counts versus rank. They show broad distributions that are not power laws, in contrast to the case when disconnected subgraphs are included.

  20. A survey of motif discovery methods in an integrated framework

    PubMed Central

    Sandve, Geir Kjetil; Drabløs, Finn

    2006-01-01

    Background There has been a growing interest in computational discovery of regulatory elements, and a multitude of motif discovery methods have been proposed. Computational motif discovery has been used with some success in simple organisms like yeast. However, as we move to higher organisms with more complex genomes, more sensitive methods are needed. Several recent methods try to integrate additional sources of information, including microarray experiments (gene expression and ChlP-chip). There is also a growing awareness that regulatory elements work in combination, and that this combinatorial behavior must be modeled for successful motif discovery. However, the multitude of methods and approaches makes it difficult to get a good understanding of the current status of the field. Results This paper presents a survey of methods for motif discovery in DNA, based on a structured and well defined framework that integrates all relevant elements. Existing methods are discussed according to this framework. Conclusion The survey shows that although no single method takes all relevant elements into consideration, a very large number of different models treating the various elements separately have been tried. Very often the choices that have been made are not explicitly stated, making it difficult to compare different implementations. Also, the tests that have been used are often not comparable. Therefore, a stringent framework and improved test methods are needed to evaluate the different approaches in order to conclude which ones are most promising. Reviewers: This article was reviewed by Eugene V. Koonin, Philipp Bucher (nominated by Mikhail Gelfand) and Frank Eisenhaber. PMID:16600018

  1. Structural assessment of glycyl mutations in invariantly conserved motifs.

    PubMed

    Prakash, Tulika; Sandhu, Kuljeet Singh; Singh, Nitin Kumar; Bhasin, Yasha; Ramakrishnan, C; Brahmachari, Samir K

    2007-11-15

    Motifs that are evolutionarily conserved in proteins are crucial to their structure and function. In one of our earlier studies, we demonstrated that the conserved motifs occurring invariantly across several organisms could act as structural determinants of the proteins. We observed the abundance of glycyl residues in these invariantly conserved motifs. The role of glycyl residues in highly conserved motifs has not been studied extensively. Thus, it would be interesting to examine the structural perturbations induced by mutation in these conserved glycyl sites. In this work, we selected a representative set of invariant signature (IS) peptides for which both the PDB structure and mutation information was available. We thoroughly analyzed the conformational features of the glycyl sites and their local interactions with the surrounding residues. Using Ramachandran angles, we showed that the glycyl residues occurring in these IS peptides, which have undergone mutation, occurred more often in the L-disallowed as compared with the L-allowed region of the Ramachandran plot. Short range contacts around the mutation site were analyzed to study the steric effects. With the results obtained from our analysis, we hypothesize that any change of activity arising because of such mutations must be attributed to the long-range interaction(s) of the new residue if the glycyl residue in the IS peptide occurred in the L-allowed region of the Ramachandran plot. However, the mutation of those conserved glycyl residues that occurred in the L-disallowed region of the Ramachandran plot might lead to an altered activity of the protein as a result of an altered conformation of the backbone in the immediate vicinity of the glycyl residue, in addition to long range effects arising from the long side chains of the new residue. Thus, the loss of activity because of mutation in the conserved glycyl site might either relate to long range interactions or to local perturbations around the site

  2. A Combinatorial Code for Splicing Silencing: UAGG and GGGG Motifs

    PubMed Central

    An, Ping; Burge, Christopher B

    2005-01-01

    Alternative pre-mRNA splicing is widely used to regulate gene expression by tuning the levels of tissue-specific mRNA isoforms. Few regulatory mechanisms are understood at the level of combinatorial control despite numerous sequences, distinct from splice sites, that have been shown to play roles in splicing enhancement or silencing. Here we use molecular approaches to identify a ternary combination of exonic UAGG and 5′-splice-site-proximal GGGG motifs that functions cooperatively to silence the brain-region-specific CI cassette exon (exon 19) of the glutamate NMDA R1 receptor (GRIN1) transcript. Disruption of three components of the motif pattern converted the CI cassette into a constitutive exon, while predominant skipping was conferred when the same components were introduced, de novo, into a heterologous constitutive exon. Predominant exon silencing was directed by the motif pattern in the presence of six competing exonic splicing enhancers, and this effect was retained after systematically repositioning the two exonic UAGGs within the CI cassette. In this system, hnRNP A1 was shown to mediate silencing while hnRNP H antagonized silencing. Genome-wide computational analysis combined with RT-PCR testing showed that a class of skipped human and mouse exons can be identified by searches that preserve the sequence and spatial configuration of the UAGG and GGGG motifs. This analysis suggests that the multi-component silencing code may play an important role in the tissue-specific regulation of the CI cassette exon, and that it may serve more generally as a molecular language to allow for intricate adjustments and the coordination of splicing patterns from different genes. PMID:15828859

  3. Graph animals, subgraph sampling, and motif search in large networks

    NASA Astrophysics Data System (ADS)

    Baskerville, Kim; Grassberger, Peter; Paczuski, Maya

    2007-09-01

    We generalize a sampling algorithm for lattice animals (connected clusters on a regular lattice) to a Monte Carlo algorithm for “graph animals,” i.e., connected subgraphs in arbitrary networks. As with the algorithm in [N. Kashtan , Bioinformatics 20, 1746 (2004)], it provides a weighted sample, but the computation of the weights is much faster (linear in the size of subgraphs, instead of superexponential). This allows subgraphs with up to ten or more nodes to be sampled with very high statistics, from arbitrarily large networks. Using this together with a heuristic algorithm for rapidly classifying isomorphic graphs, we present results for two protein interaction networks obtained using the tandem affinity purification (TAP) method: one of Escherichia coli with 230 nodes and 695 links, and one for yeast (Saccharomyces cerevisiae) with roughly ten times more nodes and links. We find in both cases that most connected subgraphs are strong motifs ( Z scores >10 ) or antimotifs ( Z scores <-10 ) when the null model is the ensemble of networks with fixed degree sequence. Strong differences appear between the two networks, with dominant motifs in E. coli being (nearly) bipartite graphs and having many pairs of nodes that connect to the same neighbors, while dominant motifs in yeast tend towards completeness or contain large cliques. We also explore a number of methods that do not rely on measurements of Z scores or comparisons with null models. For instance, we discuss the influence of specific complexes like the 26S proteasome in yeast, where a small number of complexes dominate the k cores with large k and have a decisive effect on the strongest motifs with 6-8 nodes. We also present Zipf plots of counts versus rank. They show broad distributions that are not power laws, in contrast to the case when disconnected subgraphs are included.

  4. Motif, the basics: an overview of the widget set

    SciTech Connect

    McClurg, F.R.

    1992-10-01

    The Motif library provides programmers with a rich set of tools for building a graphical user interface with a three-dimensional appearance and a consistent method of interaction for controlling an Unix application. This Xt-based, high-level library presents an object-oriented'' approach to program design for programmers and allows end-users the flexibility to modify attributes of the interface.

  5. Motif, the basics: an overview of the widget set

    SciTech Connect

    McClurg, F.R.

    1992-10-01

    The Motif library provides programmers with a rich set of tools for building a graphical user interface with a three-dimensional appearance and a consistent method of interaction for controlling an Unix application. This Xt-based, high-level library presents an ``object-oriented`` approach to program design for programmers and allows end-users the flexibility to modify attributes of the interface.

  6. Structure and ubiquitin binding of the ubiquitin-interacting motif

    SciTech Connect

    Fisher,R.; Wang, B.; Alam, S.; Higginson, D.; Robinson, H.; Sundquist, C.; Hill, C.

    2003-01-01

    Ubiquitylation is used to target proteins into a large number of different biological processes including proteasomal degradation, endocytosis, virus budding, and vacuolar protein sorting (Vps). Ubiquitylated proteins are typically recognized using one of several different conserved ubiquitin binding modules. Here, we report the crystal structure and ubiquitin binding properties of one such module, the ubiquitin-interacting motif (UIM). We found that UIM peptides from several proteins involved in endocytosis and vacuolar protein sorting including Hrs, Vps27p, Stam1, and Eps15 bound specifically, but with modest affinity (K{sub d} = 0.1-1 mM), to free ubiquitin. Full affinity ubiquitin binding required the presence of conserved acidic patches at the N and C terminus of the UIM, as well as highly conserved central alanine and serine residues. NMR chemical shift perturbation mapping experiments demonstrated that all of these UIM peptides bind to the I44 surface of ubiquitin. The 1.45 {angstrom} resolution crystal structure of the second yeast Vps27p UIM (Vps27p-2) revealed that the ubiquitin-interacting motif forms an amphipathic helix. Although Vps27p-2 is monomeric in solution, the motif unexpectedly crystallized as an antiparallel four-helix bundle, and the potential biological implications of UIM oligomerization are therefore discussed.

  7. Maximum likelihood density modification by pattern recognition of structural motifs

    DOEpatents

    Terwilliger, Thomas C.

    2004-04-13

    An electron density for a crystallographic structure having protein regions and solvent regions is improved by maximizing the log likelihood of a set of structures factors {F.sub.h } using a local log-likelihood function: (x)+p(.rho.(x).vertline.SOLV)p.sub.SOLV (x)+p(.rho.(x).vertline.H)p.sub.H (x)], where p.sub.PROT (x) is the probability that x is in the protein region, p(.rho.(x).vertline.PROT) is the conditional probability for .rho.(x) given that x is in the protein region, and p.sub.SOLV (x) and p(.rho.(x).vertline.SOLV) are the corresponding quantities for the solvent region, p.sub.H (x) refers to the probability that there is a structural motif at a known location, with a known orientation, in the vicinity of the point x; and p(.rho.(x).vertline.H) is the probability distribution for electron density at this point given that the structural motif actually is present. One appropriate structural motif is a helical structure within the crystallographic structure.

  8. Retroviruses integrate into a shared, non-palindromic DNA motif.

    PubMed

    Kirk, Paul D W; Huvet, Maxime; Melamed, Anat; Maertens, Goedele N; Bangham, Charles R M

    2016-11-14

    Many DNA-binding factors, such as transcription factors, form oligomeric complexes with structural symmetry that bind to palindromic DNA sequences(1). Palindromic consensus nucleotide sequences are also found at the genomic integration sites of retroviruses(2-6) and other transposable elements(7-9), and it has been suggested that this palindromic consensus arises as a consequence of the structural symmetry in the integrase complex(2,3). However, we show here that the palindromic consensus sequence is not present in individual integration sites of human T-cell lymphotropic virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1), but arises in the population average as a consequence of the existence of a non-palindromic nucleotide motif that occurs in approximately equal proportions on the plus strand and the minus strand of the host genome. We develop a generally applicable algorithm to sort the individual integration site sequences into plus-strand and minus-strand subpopulations, and use this to identify the integration site nucleotide motifs of five retroviruses of different genera: HTLV-1, HIV-1, murine leukaemia virus (MLV), avian sarcoma leucosis virus (ASLV) and prototype foamy virus (PFV). The results reveal a non-palindromic motif that is shared between these retroviruses.

  9. STEME: efficient EM to find motifs in large data sets.

    PubMed

    Reid, John E; Wernisch, Lorenz

    2011-10-01

    MEME and many other popular motif finders use the expectation-maximization (EM) algorithm to optimize their parameters. Unfortunately, the running time of EM is linear in the length of the input sequences. This can prohibit its application to data sets of the size commonly generated by high-throughput biological techniques. A suffix tree is a data structure that can efficiently index a set of sequences. We describe an algorithm, Suffix Tree EM for Motif Elicitation (STEME), that approximates EM using suffix trees. To the best of our knowledge, this is the first application of suffix trees to EM. We provide an analysis of the expected running time of the algorithm and demonstrate that STEME runs an order of magnitude more quickly than the implementation of EM used by MEME. We give theoretical bounds for the quality of the approximation and show that, in practice, the approximation has a negligible effect on the outcome. We provide an open source implementation of the algorithm that we hope will be used to speed up existing and future motif search algorithms.

  10. Caveats in modeling a common motif in genetic circuits

    NASA Astrophysics Data System (ADS)

    Labavić, Darka; Nagel, Hannes; Janke, Wolfhard; Meyer-Ortmanns, Hildegard

    2013-06-01

    From a coarse-grained perspective, the motif of a self-activating species, activating a second species that acts as its own repressor, is widely found in biological systems, in particular in genetic systems with inherent oscillatory behavior. Here we consider a specific realization of this motif as a genetic circuit, termed the bistable frustrated unit, in which genes are described as directly producing proteins. Upon an improved resolution in time, we focus on the effect that inherent time scales on the underlying scale can have on the bifurcation patterns on a coarser scale. Time scales are set by the binding and unbinding rates of the transcription factors to the promoter regions of the genes. Depending on the ratio of these rates to the decay times of both proteins, the appropriate averaging procedure for obtaining a coarse-grained description changes and leads to sets of deterministic equations, which considerably differ in their bifurcation structure. In particular, the desired intermediate range of regular limit cycles fades away when the binding rates of genes are not fast as compared to the decay time of the proteins. Our analysis illustrates that the common topology of the widely found motif alone does not imply universal features in the dynamics.

  11. An update on cell surface proteins containing extensin-motifs.

    PubMed

    Borassi, Cecilia; Sede, Ana R; Mecchia, Martin A; Salgado Salter, Juan D; Marzol, Eliana; Muschietti, Jorge P; Estevez, Jose M

    2016-01-01

    In recent years it has become clear that there are several molecular links that interconnect the plant cell surface continuum, which is highly important in many biological processes such as plant growth, development, and interaction with the environment. The plant cell surface continuum can be defined as the space that contains and interlinks the cell wall, plasma membrane and cytoskeleton compartments. In this review, we provide an updated view of cell surface proteins that include modular domains with an extensin (EXT)-motif followed by a cytoplasmic kinase-like domain, known as PERKs (for proline-rich extensin-like receptor kinases); with an EXT-motif and an actin binding domain, known as formins; and with extracellular hybrid-EXTs. We focus our attention on the EXT-motifs with the short sequence Ser-Pro(3-5), which is found in several different protein contexts within the same extracellular space, highlighting a putative conserved structural and functional role. A closer understanding of the dynamic regulation of plant cell surface continuum and its relationship with the downstream signalling cascade is a crucial forthcoming challenge.

  12. The bioactive acidic serine- and aspartate-rich motif peptide.

    PubMed

    Minamizaki, Tomoko; Yoshiko, Yuji

    2015-01-01

    The organic component of the bone matrix comprises 40% dry weight of bone. The organic component is mostly composed of type I collagen and small amounts of non-collagenous proteins (NCPs) (10-15% of the total bone protein content). The small integrin-binding ligand N-linked glycoprotein (SIBLING) family, a NCP, is considered to play a key role in bone mineralization. SIBLING family of proteins share common structural features and includes the arginine-glycine-aspartic acid (RGD) motif and acidic serine- and aspartic acid-rich motif (ASARM). Clinical manifestations of gene mutations and/or genetically modified mice indicate that SIBLINGs play diverse roles in bone and extraskeletal tissues. ASARM peptides might not be primary responsible for the functional diversity of SIBLINGs, but this motif is suggested to be a key domain of SIBLINGs. However, the exact function of ASARM peptides is poorly understood. In this article, we discuss the considerable progress made in understanding the role of ASARM as a bioactive peptide.

  13. QuateXelero: An Accelerated Exact Network Motif Detection Algorithm

    PubMed Central

    Khakabimamaghani, Sahand; Sharafuddin, Iman; Dichter, Norbert; Koch, Ina; Masoudi-Nejad, Ali

    2013-01-01

    Finding motifs in biological, social, technological, and other types of networks has become a widespread method to gain more knowledge about these networks’ structure and function. However, this task is very computationally demanding, because it is highly associated with the graph isomorphism which is an NP problem (not known to belong to P or NP-complete subsets yet). Accordingly, this research is endeavoring to decrease the need to call NAUTY isomorphism detection method, which is the most time-consuming step in many existing algorithms. The work provides an extremely fast motif detection algorithm called QuateXelero, which has a Quaternary Tree data structure in the heart. The proposed algorithm is based on the well-known ESU (FANMOD) motif detection algorithm. The results of experiments on some standard model networks approve the overal superiority of the proposed algorithm, namely QuateXelero, compared with two of the fastest existing algorithms, G-Tries and Kavosh. QuateXelero is especially fastest in constructing the central data structure of the algorithm from scratch based on the input network. PMID:23874498

  14. A novel swarm intelligence algorithm for finding DNA motifs.

    PubMed

    Lei, Chengwei; Ruan, Jianhua

    2009-01-01

    Discovering DNA motifs from co-expressed or co-regulated genes is an important step towards deciphering complex gene regulatory networks and understanding gene functions. Despite significant improvement in the last decade, it still remains one of the most challenging problems in computational molecular biology. In this work, we propose a novel motif finding algorithm that finds consensus patterns using a population-based stochastic optimisation technique called Particle Swarm Optimisation (PSO), which has been shown to be effective in optimising difficult multidimensional problems in continuous domains. We propose to use a word dissimilarity graph to remap the neighborhood structure of the solution space of DNA motifs, and propose a modification of the naive PSO algorithm to accommodate discrete variables. In order to improve efficiency, we also propose several strategies for escaping from local optima and for automatically determining the termination criteria. Experimental results on simulated challenge problems show that our method is both more efficient and more accurate than several existing algorithms. Applications to several sets of real promoter sequences also show that our approach is able to detect known transcription factor binding sites, and outperforms two of the most popular existing algorithms.

  15. MAR characteristic motifs mediate episomal vector in CHO cells.

    PubMed

    Lin, Yan; Li, Zhaoxi; Wang, Tianyun; Wang, Xiaoyin; Wang, Li; Dong, Weihua; Jing, Changqin; Yang, Xianjun

    2015-04-01

    An ideal gene therapy vector should enable persistent transgene expression without limitations in safety and reproducibility. Recent researches' insight into the ability of chromosomal matrix attachment regions (MARs) to mediate episomal maintenance of genetic elements allowed the development of a circular episomal vector. Although a MAR-mediated engineered vector has been developed, little is known on which motifs of MAR confer this function during interaction with the host genome. Here, we report an artificially synthesized DNA fragment containing only characteristic motif sequences that served as an alternative to human beta-interferon matrix attachment region sequence. The potential of the vector to mediate gene transfer in CHO cells was investigated. The short synthetic MAR motifs were found to mediate episomal vector at a low copy number for many generations without integration into the host genome. Higher transgene expression was maintained for at least 4 months. In addition, MAR was maintained episomally and conferred sustained EGFP expression even in nonselective CHO cells. All the results demonstrated that MAR characteristic sequence-based vector can function as stable episomes in CHO cells, supporting long-term and effective transgene expression.

  16. Event Networks and the Identification of Crime Pattern Motifs

    PubMed Central

    2015-01-01

    In this paper we demonstrate the use of network analysis to characterise patterns of clustering in spatio-temporal events. Such clustering is of both theoretical and practical importance in the study of crime, and forms the basis for a number of preventative strategies. However, existing analytical methods show only that clustering is present in data, while offering little insight into the nature of the patterns present. Here, we show how the classification of pairs of events as close in space and time can be used to define a network, thereby generalising previous approaches. The application of graph-theoretic techniques to these networks can then offer significantly deeper insight into the structure of the data than previously possible. In particular, we focus on the identification of network motifs, which have clear interpretation in terms of spatio-temporal behaviour. Statistical analysis is complicated by the nature of the underlying data, and we provide a method by which appropriate randomised graphs can be generated. Two datasets are used as case studies: maritime piracy at the global scale, and residential burglary in an urban area. In both cases, the same significant 3-vertex motif is found; this result suggests that incidents tend to occur not just in pairs, but in fact in larger groups within a restricted spatio-temporal domain. In the 4-vertex case, different motifs are found to be significant in each case, suggesting that this technique is capable of discriminating between clustering patterns at a finer granularity than previously possible. PMID:26605544

  17. Event Networks and the Identification of Crime Pattern Motifs.

    PubMed

    Davies, Toby; Marchione, Elio

    2015-01-01

    In this paper we demonstrate the use of network analysis to characterise patterns of clustering in spatio-temporal events. Such clustering is of both theoretical and practical importance in the study of crime, and forms the basis for a number of preventative strategies. However, existing analytical methods show only that clustering is present in data, while offering little insight into the nature of the patterns present. Here, we show how the classification of pairs of events as close in space and time can be used to define a network, thereby generalising previous approaches. The application of graph-theoretic techniques to these networks can then offer significantly deeper insight into the structure of the data than previously possible. In particular, we focus on the identification of network motifs, which have clear interpretation in terms of spatio-temporal behaviour. Statistical analysis is complicated by the nature of the underlying data, and we provide a method by which appropriate randomised graphs can be generated. Two datasets are used as case studies: maritime piracy at the global scale, and residential burglary in an urban area. In both cases, the same significant 3-vertex motif is found; this result suggests that incidents tend to occur not just in pairs, but in fact in larger groups within a restricted spatio-temporal domain. In the 4-vertex case, different motifs are found to be significant in each case, suggesting that this technique is capable of discriminating between clustering patterns at a finer granularity than previously possible.

  18. Automatic Network Fingerprinting through Single-Node Motifs

    PubMed Central

    Echtermeyer, Christoph; da Fontoura Costa, Luciano; Rodrigues, Francisco A.; Kaiser, Marcus

    2011-01-01

    Complex networks have been characterised by their specific connectivity patterns (network motifs), but their building blocks can also be identified and described by node-motifs—a combination of local network features. One technique to identify single node-motifs has been presented by Costa et al. (L. D. F. Costa, F. A. Rodrigues, C. C. Hilgetag, and M. Kaiser, Europhys. Lett., 87, 1, 2009). Here, we first suggest improvements to the method including how its parameters can be determined automatically. Such automatic routines make high-throughput studies of many networks feasible. Second, the new routines are validated in different network-series. Third, we provide an example of how the method can be used to analyse network time-series. In conclusion, we provide a robust method for systematically discovering and classifying characteristic nodes of a network. In contrast to classical motif analysis, our approach can identify individual components (here: nodes) that are specific to a network. Such special nodes, as hubs before, might be found to play critical roles in real-world networks. PMID:21297963

  19. Determination of Sectional Constancy of Organic Coal-Water Fuel Compositions

    NASA Astrophysics Data System (ADS)

    Dmitrienko, Margarita A.; Nyashina, Galina S.; Strizhak, Pavel A.

    2016-02-01

    To use widespreadly the waste of coals and oils processing in the great and the small-scale power generation, the key parameter, which is sectional constancy of promising organic coal-water fuels (OCWF), was studied. The compo-sitions of OCWF from brown and bituminous coals, filter cakes, used motor, turbine and dielectrical oils, water-oil emul-sion and special wetting agent (plasticizer) were investigated. Two modes of preparation were considered. They are with homogenizer and cavitator. It was established that the constancy did not exceed 5-7 days for the compositions of OCWF with brown coals, and 12-15 days for that compositions with bituminous coals and filter cakes. The injection of used oils in a composition of OCWF led to increase in viscosity of fuel compositions and their sectional constancy.

  20. A combinatorial approach to the repertoire of RNA kissing motifs; towards multiplex detection by switching hairpin aptamers

    PubMed Central

    Durand, Guillaume; Dausse, Eric; Goux, Emma; Fiore, Emmanuelle; Peyrin, Eric; Ravelet, Corinne; Toulmé, Jean-Jacques

    2016-01-01

    Loop–loop (also known as kissing) interactions between RNA hairpins are involved in several mechanisms in both prokaryotes and eukaryotes such as the regulation of the plasmid copy number or the dimerization of retroviral genomes. The stability of kissing complexes relies on loop parameters (base composition, sequence and size) and base combination at the loop–loop helix - stem junctions. In order to identify kissing partners that could be used as regulatory elements or building blocks of RNA scaffolds, we analysed a pool of 5.2 × 106 RNA hairpins with randomized loops. We identified more than 50 pairs of kissing RNA hairpins. Two kissing motifs, 5′CCNY and 5′RYRY, generate highly stable complexes with KDs in the low nanomolar range. Such motifs were introduced in the apical loop of hairpin aptamers that switch between unfolded and folded state upon binding to their cognate target molecule, hence their name aptaswitch. The aptaswitch–ligand complex is specifically recognized by a second RNA hairpin named aptakiss through loop–loop interaction. Taking advantage of our kissing motif repertoire we engineered aptaswitch–aptakiss modules for purine derivatives, namely adenosine, GTP and theophylline and demonstrated that these molecules can be specifically and simultaneously detected by surface plasmon resonance or by fluorescence anisotropy. PMID:27067541

  1. A Novel Bayesian DNA Motif Comparison Method for Clustering and Retrieval

    PubMed Central

    Margalit, Hanah; Friedman, Nir

    2008-01-01

    Characterizing the DNA-binding specificities of transcription factors is a key problem in computational biology that has been addressed by multiple algorithms. These usually take as input sequences that are putatively bound by the same factor and output one or more DNA motifs. A common practice is to apply several such algorithms simultaneously to improve coverage at the price of redundancy. In interpreting such results, two tasks are crucial: clustering of redundant motifs, and attributing the motifs to transcription factors by retrieval of similar motifs from previously characterized motif libraries. Both tasks inherently involve motif comparison. Here we present a novel method for comparing and merging motifs, based on Bayesian probabilistic principles. This method takes into account both the similarity in positional nucleotide distributions of the two motifs and their dissimilarity to the background distribution. We demonstrate the use of the new comparison method as a basis for motif clustering and retrieval procedures, and compare it to several commonly used alternatives. Our results show that the new method outperforms other available methods in accuracy and sensitivity. We incorporated the resulting motif clustering and retrieval procedures in a large-scale automated pipeline for analyzing DNA motifs. This pipeline integrates the results of various DNA motif discovery algorithms and automatically merges redundant motifs from multiple training sets into a coherent annotated library of motifs. Application of this pipeline to recent genome-wide transcription factor location data in S. cerevisiae successfully identified DNA motifs in a manner that is as good as semi-automated analysis reported in the literature. Moreover, we show how this analysis elucidates the mechanisms of condition-specific preferences of transcription factors. PMID:18463706

  2. Decreased RNA-binding motif 5 expression is associated with tumor progression in gastric cancer.

    PubMed

    Kobayashi, Takahiko; Ishida, Junich; Shimizu, Yuichi; Kawakami, Hiroshi; Suda, Goki; Muranaka, Tetsuhito; Komatsu, Yoshito; Asaka, Masahiro; Sakamoto, Naoya

    2017-03-01

    RNA-binding motif 5 is a putative tumor suppressor gene that modulates cell cycle arrest and apoptosis. We recently demonstrated that RNA-binding motif 5 inhibits cell growth through the p53 pathway. This study evaluated the clinical significance of RNA-binding motif 5 expression in gastric cancer and the effects of altered RNA-binding motif 5 expression on cancer biology in gastric cancer cells. RNA-binding motif 5 protein expression was evaluated by immunohistochemistry using the surgical specimens of 106 patients with gastric cancer. We analyzed the relationships of RNA-binding motif 5 expression with clinicopathological parameters and patient prognosis. We further explored the effects of RNA-binding motif 5 downregulation with short hairpin RNA on cell growth and p53 signaling in MKN45 gastric cancer cells. Immunohistochemistry revealed that RNA-binding motif 5 expression was decreased in 29 of 106 (27.4%) gastric cancer specimens. Decreased RNA-binding motif 5 expression was correlated with histological differentiation, depth of tumor infiltration, nodal metastasis, tumor-node-metastasis stage, and prognosis. RNA-binding motif 5 silencing enhanced gastric cancer cell proliferation and decreased p53 transcriptional activity in reporter gene assays. Conversely, restoration of RNA-binding motif 5 expression suppressed cell growth and recovered p53 transactivation in RNA-binding motif 5-silenced cells. Furthermore, RNA-binding motif 5 silencing reduced the messenger RNA and protein expression of the p53 target gene p21. Our results suggest that RNA-binding motif 5 downregulation is involved in gastric cancer progression and that RNA-binding motif 5 behaves as a tumor suppressor gene in gastric cancer.

  3. Genome-Wide Motif Statistics are Shaped by DNA Binding Proteins over Evolutionary Time Scales

    NASA Astrophysics Data System (ADS)

    Qian, Long; Kussell, Edo

    2016-10-01

    The composition of a genome with respect to all possible short DNA motifs impacts the ability of DNA binding proteins to locate and bind their target sites. Since nonfunctional DNA binding can be detrimental to cellular functions and ultimately to organismal fitness, organisms could benefit from reducing the number of nonfunctional DNA binding sites genome wide. Using in vitro measurements of binding affinities for a large collection of DNA binding proteins, in multiple species, we detect a significant global avoidance of weak binding sites in genomes. We demonstrate that the underlying evolutionary process leaves a distinct genomic hallmark in that similar words have correlated frequencies, a signal that we detect in all species across domains of life. We consider the possibility that natural selection against weak binding sites contributes to this process, and using an evolutionary model we show that the strength of selection needed to maintain global word compositions is on the order of point mutation rates. Likewise, we show that evolutionary mechanisms based on interference of protein-DNA binding with replication and mutational repair processes could yield similar results and operate with similar rates. On the basis of these modeling and bioinformatic results, we conclude that genome-wide word compositions have been molded by DNA binding proteins acting through tiny evolutionary steps over time scales spanning millions of generations.

  4. Identification of cancer-related genes and motifs in the human gene regulatory network.

    PubMed

    Carson, Matthew B; Gu, Jianlei; Yu, Guangjun; Lu, Hui

    2015-08-01

    The authors investigated the regulatory network motifs and corresponding motif positions of cancer-related genes. First, they mapped disease-related genes to a transcription factor regulatory network. Next, they calculated statistically significant motifs and subsequently identified positions within these motifs that were enriched in cancer-related genes. Potential mechanisms of these motifs and positions are discussed. These results could be used to identify other disease- and cancer-related genes and could also suggest mechanisms for how these genes relate to co-occurring diseases.

  5. Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer

    PubMed Central

    Chen, Zhong; Lan, Xun; Thomas-Ahner, Jennifer M; Wu, Dayong; Liu, Xiangtao; Ye, Zhenqing; Wang, Liguo; Sunkel, Benjamin; Grenade, Cassandra; Chen, Junsheng; Zynger, Debra L; Yan, Pearlly S; Huang, Jiaoti; Nephew, Kenneth P; Huang, Tim H-M; Lin, Shili; Clinton, Steven K; Li, Wei; Jin, Victor X; Wang, Qianben

    2015-01-01

    Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific motifs. By using a motif-resolution chromatin immunoprecipitation-exonuclease (ChIP-exo) approach, we find that agonist-liganded human androgen receptor (AR) and antagonist-liganded AR bind to two distinctly different motifs, leading to distinct transcriptional outcomes in prostate cancer cells. Further analysis on clinical prostate tissues reveals that the binding of AR to these two distinct motifs is involved in prostate carcinogenesis. Together, these results suggest that unique ligands may switch DNA motifs recognized by ligand-dependent transcription factors in vivo. Our findings also provide a broad mechanistic foundation for understanding ligand-specific induction of gene expression profiles. PMID:25535248

  6. DNA nanotechnology based on i-motif structures.

    PubMed

    Dong, Yuanchen; Yang, Zhongqiang; Liu, Dongsheng

    2014-06-17

    CONSPECTUS: Most biological processes happen at the nanometer scale, and understanding the energy transformations and material transportation mechanisms within living organisms has proved challenging. To better understand the secrets of life, researchers have investigated artificial molecular motors and devices over the past decade because such systems can mimic certain biological processes. DNA nanotechnology based on i-motif structures is one system that has played an important role in these investigations. In this Account, we summarize recent advances in functional DNA nanotechnology based on i-motif structures. The i-motif is a DNA quadruplex that occurs as four stretches of cytosine repeat sequences form C·CH(+) base pairs, and their stabilization requires slightly acidic conditions. This unique property has produced the first DNA molecular motor driven by pH changes. The motor is reliable, and studies show that it is capable of millisecond running speeds, comparable to the speed of natural protein motors. With careful design, the output of these types of motors was combined to drive micrometer-sized cantilevers bend. Using established DNA nanostructure assembly and functionalization methods, researchers can easily integrate the motor within other DNA assembled structures and functional units, producing DNA molecular devices with new functions such as suprahydrophobic/suprahydrophilic smart surfaces that switch, intelligent nanopores triggered by pH changes, molecular logic gates, and DNA nanosprings. Recently, researchers have produced motors driven by light and electricity, which have allowed DNA motors to be integrated within silicon-based nanodevices. Moreover, some devices based on i-motif structures have proven useful for investigating processes within living cells. The pH-responsiveness of the i-motif structure also provides a way to control the stepwise assembly of DNA nanostructures. In addition, because of the stability of the i-motif, this

  7. Motif discovery with data mining in 3D protein structure databases: discovery, validation and prediction of the U-shape zinc binding ("Huf-Zinc") motif.

    PubMed

    Maurer-Stroh, Sebastian; Gao, He; Han, Hao; Baeten, Lies; Schymkowitz, Joost; Rousseau, Frederic; Zhang, Louxin; Eisenhaber, Frank

    2013-02-01

    Data mining in protein databases, derivatives from more fundamental protein 3D structure and sequence databases, has considerable unearthed potential for the discovery of sequence motif--structural motif--function relationships as the finding of the U-shape (Huf-Zinc) motif, originally a small student's project, exemplifies. The metal ion zinc is critically involved in universal biological processes, ranging from protein-DNA complexes and transcription regulation to enzymatic catalysis and metabolic pathways. Proteins have evolved a series of motifs to specifically recognize and bind zinc ions. Many of these, so called zinc fingers, are structurally independent globular domains with discontinuous binding motifs made up of residues mostly far apart in sequence. Through a systematic approach starting from the BRIX structure fragment database, we discovered that there exists another predictable subset of zinc-binding motifs that not only have a conserved continuous sequence pattern but also share a characteristic local conformation, despite being included in totally different overall folds. While this does not allow general prediction of all Zn binding motifs, a HMM-based web server, Huf-Zinc, is available for prediction of these novel, as well as conventional, zinc finger motifs in protein sequences. The Huf-Zinc webserver can be freely accessed through this URL (http://mendel.bii.a-star.edu.sg/METHODS/hufzinc/).

  8. CENTDIST: discovery of co-associated factors by motif distribution

    PubMed Central

    Zhang, Zhizhuo; Chang, Cheng Wei; Goh, Wan Ling; Sung, Wing-Kin; Cheung, Edwin

    2011-01-01

    Transcription factors (TFs) do not function alone but work together with other TFs (called co-TFs) in a combinatorial fashion to precisely control the transcription of target genes. Mining co-TFs is thus important to understand the mechanism of transcriptional regulation. Although existing methods can identify co-TFs, their accuracy depends heavily on the chosen background model and other parameters such as the enrichment window size and the PWM score cut-off. In this study, we have developed a novel web-based co-motif scanning program called CENTDIST (http://compbio.ddns.comp.nus.edu.sg/~chipseq/centdist/). In comparison to current co-motif scanning programs, CENTDIST does not require the input of any user-specific parameters and background information. Instead, CENTDIST automatically determines the best set of parameters and ranks co-TF motifs based on their distribution around ChIP-seq peaks. We tested CENTDIST on 14 ChIP-seq data sets and found CENTDIST is more accurate than existing methods. In particular, we applied CENTDIST on an Androgen Receptor (AR) ChIP-seq data set from a prostate cancer cell line and correctly predicted all known co-TFs (eight TFs) of AR in the top 20 hits as well as discovering AP4 as a novel co-TF of AR (which was missed by existing methods). Taken together, CENTDIST, which exploits the imbalanced nature of co-TF binding, is a user-friendly, parameter-less and powerful predictive web-based program for understanding the mechanism of transcriptional co-regulation. PMID:21602269

  9. Identification of imine reductase-specific sequence motifs.

    PubMed

    Fademrecht, Silvia; Scheller, Philipp N; Nestl, Bettina M; Hauer, Bernhard; Pleiss, Jürgen

    2016-05-01

    Chiral amines are valuable building blocks for the production of a variety of pharmaceuticals, agrochemicals and other specialty chemicals. Only recently, imine reductases (IREDs) were discovered which catalyze the stereoselective reduction of imines to chiral amines. Although several IREDs were biochemically characterized in the last few years, knowledge of the reaction mechanism and the molecular basis of substrate specificity and stereoselectivity is limited. To gain further insights into the sequence-function relationships, the Imine Reductase Engineering Database (www.IRED.BioCatNet.de) was established and a systematic analysis of 530 putative IREDs was performed. A standard numbering scheme based on R-IRED-Sk was introduced to facilitate the identification and communication of structurally equivalent positions in different proteins. A conservation analysis revealed a highly conserved cofactor binding region and a predominantly hydrophobic substrate binding cleft. Two IRED-specific motifs were identified, the cofactor binding motif GLGxMGx(5 )[ATS]x(4) Gx(4) [VIL]WNR[TS]x(2) [KR] and the active site motif Gx[DE]x[GDA]x[APS]x(3){K}x[ASL]x[LMVIAG]. Our results indicate a preference toward NADPH for all IREDs and explain why, despite their sequence similarity to β-hydroxyacid dehydrogenases (β-HADs), no conversion of β-hydroxyacids has been observed. Superfamily-specific conservations were investigated to explore the molecular basis of their stereopreference. Based on our analysis and previous experimental results on IRED mutants, an exclusive role of standard position 187 for stereoselectivity is excluded. Alternatively, two standard positions 139 and 194 were identified which are superfamily-specifically conserved and differ in R- and S-selective enzymes.

  10. The Assembly Motif of a Bacterial Small Multidrug Resistance Protein*

    PubMed Central

    Poulsen, Bradley E.; Rath, Arianna; Deber, Charles M.

    2009-01-01

    Multidrug transporters such as the small multidrug resistance (SMR) family of bacterial integral membrane proteins are capable of conferring clinically significant resistance to a variety of common therapeutics. As antiporter proteins of ∼100 amino acids, SMRs must self-assemble into homo-oligomeric structures for efflux of drug molecules. Oligomerization centered at transmembrane helix four (TM4) has been implicated in SMR assembly, but the full complement of residues required to mediate its self-interaction remains to be characterized. Here, we use Hsmr, the 110-residue SMR family member of the archaebacterium Halobacterium salinarum, to determine the TM4 residue motif required to mediate drug resistance and SMR self-association. Twelve single point mutants that scan the central portion of the TM4 helix (residues 85–104) were constructed and were tested for their ability to confer resistance to the cytotoxic compound ethidium bromide. Six residues were found to be individually essential for drug resistance activity (Gly90, Leu91, Leu93, Ile94, Gly97, and Val98), defining a minimum activity motif of 90GLXLIXXGV98 within TM4. When the propensity of these mutants to dimerize on SDS-PAGE was examined, replacements of all but Ile resulted in ∼2-fold reduction of dimerization versus the wild-type antiporter. Our work defines a minimum activity motif of 90GLXLIXXGV98 within TM4 and suggests that this sequence mediates TM4-based SMR dimerization along a single helix surface, stabilized by a small residue heptad repeat sequence. These TM4-TM4 interactions likely constitute the highest affinity locus for disruption of SMR function by directly targeting its self-assembly mechanism. PMID:19224913

  11. Evolving DNA motifs to predict GeneChip probe performance

    PubMed Central

    Langdon, WB; Harrison, AP

    2009-01-01

    Background Affymetrix High Density Oligonuclotide Arrays (HDONA) simultaneously measure expression of thousands of genes using millions of probes. We use correlations between measurements for the same gene across 6685 human tissue samples from NCBI's GEO database to indicated the quality of individual HG-U133A probes. Low correlation indicates a poor probe. Results Regular expressions can be automatically created from a Backus-Naur form (BNF) context-free grammar using strongly typed genetic programming. Conclusion The automatically produced motif is better at predicting poor DNA sequences than an existing human generated RE, suggesting runs of Cytosine and Guanine and mixtures should all be avoided. PMID:19298675

  12. Nucleic Acid i-Motif Structures in Analytical Chemistry.

    PubMed

    Alba, Joan Josep; Sadurní, Anna; Gargallo, Raimundo

    2016-09-02

    Under the appropriate experimental conditions of pH and temperature, cytosine-rich segments in DNA or RNA sequences may produce a characteristic folded structure known as an i-motif. Besides its potential role in vivo, which is still under investigation, this structure has attracted increasing interest in other fields due to its sharp, fast and reversible pH-driven conformational changes. This "on/off" switch at molecular level is being used in nanotechnology and analytical chemistry to develop nanomachines and sensors, respectively. This paper presents a review of the latest applications of this structure in the field of chemical analysis.

  13. Recurring sequence-structure motifs in (βα)8-barrel proteins and experimental optimization of a chimeric protein designed based on such motifs.

    PubMed

    Wang, Jichao; Zhang, Tongchuan; Liu, Ruicun; Song, Meilin; Wang, Juncheng; Hong, Jiong; Chen, Quan; Liu, Haiyan

    2017-02-01

    An interesting way of generating novel artificial proteins is to combine sequence motifs from natural proteins, mimicking the evolutionary path suggested by natural proteins comprising recurring motifs. We analyzed the βα and αβ modules of TIM barrel proteins by structure alignment-based sequence clustering. A number of preferred motifs were identified. A chimeric TIM was designed by using recurring elements as mutually compatible interfaces. The foldability of the designed TIM protein was then significantly improved by six rounds of directed evolution. The melting temperature has been improved by more than 20°C. A variety of characteristics suggested that the resulting protein is well-folded. Our analysis provided a library of peptide motifs that is potentially useful for different protein engineering studies. The protein engineering strategy of using recurring motifs as interfaces to connect partial natural proteins may be applied to other protein folds.

  14. Fast and Accurate Discovery of Degenerate Linear Motifs in Protein Sequences

    PubMed Central

    Levy, Emmanuel D.; Michnick, Stephen W.

    2014-01-01

    Linear motifs mediate a wide variety of cellular functions, which makes their characterization in protein sequences crucial to understanding cellular systems. However, the short length and degenerate nature of linear motifs make their discovery a difficult problem. Here, we introduce MotifHound, an algorithm particularly suited for the discovery of small and degenerate linear motifs. MotifHound performs an exact and exhaustive enumeration of all motifs present in proteins of interest, including all of their degenerate forms, and scores the overrepresentation of each motif based on its occurrence in proteins of interest relative to a background (e.g., proteome) using the hypergeometric distribution. To assess MotifHound, we benchmarked it together with state-of-the-art algorithms. The benchmark consists of 11,880 sets of proteins from S. cerevisiae; in each set, we artificially spiked-in one motif varying in terms of three key parameters, (i) number of occurrences, (ii) length and (iii) the number of degenerate or “wildcard” positions. The benchmark enabled the evaluation of the impact of these three properties on the performance of the different algorithms. The results showed that MotifHound and SLiMFinder were the most accurate in detecting degenerate linear motifs. Interestingly, MotifHound was 15 to 20 times faster at comparable accuracy and performed best in the discovery of highly degenerate motifs. We complemented the benchmark by an analysis of proteins experimentally shown to bind the FUS1 SH3 domain from S. cerevisiae. Using the full-length protein partners as sole information, MotifHound recapitulated most experimentally determined motifs binding to the FUS1 SH3 domain. Moreover, these motifs exhibited properties typical of SH3 binding peptides, e.g., high intrinsic disorder and evolutionary conservation, despite the fact that none of these properties were used as prior information. MotifHound is available (http://michnick.bcm.umontreal.ca or http

  15. SLiMDisc: short, linear motif discovery, correcting for common evolutionary descent

    PubMed Central

    Davey, Norman E.; Shields, Denis C.; Edwards, Richard J.

    2006-01-01

    Many important interactions of proteins are facilitated by short, linear motifs (SLiMs) within a protein's primary sequence. Our aim was to establish robust methods for discovering putative functional motifs. The strongest evidence for such motifs is obtained when the same motifs occur in unrelated proteins, evolving by convergence. In practise, searches for such motifs are often swamped by motifs shared in related proteins that are identical by descent. Prediction of motifs among sets of biologically related proteins, including those both with and without detectable similarity, were made using the TEIRESIAS algorithm. The number of motif occurrences arising through common evolutionary descent were normalized based on treatment of BLAST local alignments. Motifs were ranked according to a score derived from the product of the normalized number of occurrences and the information content. The method was shown to significantly outperform methods that do not discount evolutionary relatedness, when applied to known SLiMs from a subset of the eukaryotic linear motif (ELM) database. An implementation of Multiple Spanning Tree weighting outperformed two other weighting schemes, in a variety of settings. PMID:16855291

  16. Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments

    PubMed Central

    Kheradpour, Pouya; Kellis, Manolis

    2014-01-01

    Recent advances in technology have led to a dramatic increase in the number of available transcription factor ChIP-seq and ChIP-chip data sets. Understanding the motif content of these data sets is an important step in understanding the underlying mechanisms of regulation. Here we provide a systematic motif analysis for 427 human ChIP-seq data sets using motifs curated from the literature and also discovered de novo using five established motif discovery tools. We use a systematic pipeline for calculating motif enrichment in each data set, providing a principled way for choosing between motif variants found in the literature and for flagging potentially problematic data sets. Our analysis confirms the known specificity of 41 of the 56 analyzed factor groups and reveals motifs of potential cofactors. We also use cell type-specific binding to find factors active in specific conditions. The resource we provide is accessible both for browsing a small number of factors and for performing large-scale systematic analyses. We provide motif matrices, instances and enrichments in each of the ENCODE data sets. The motifs discovered here have been used in parallel studies to validate the specificity of antibodies, understand cooperativity between data sets and measure the variation of motif binding across individuals and species. PMID:24335146

  17. Small yet effective: the ethylene responsive element binding factor-associated amphiphilic repression (EAR) motif.

    PubMed

    Kagale, Sateesh; Rozwadowski, Kevin

    2010-06-01

    The Ethylene-responsive element binding factor-associated Amphiphilic Repression (EAR) motif is a small yet distinct regulatory motif that is conserved in many plant transcriptional regulator (TR) proteins associated with diverse biological functions. We have previously established a list of high-confidence Arabidopsis EAR repressors, the EAR repressome, comprising 219 TRs belonging to 21 different TR families. This class of proteins and the sequence context of the EAR motif exhibited a high degree of conservation across evolutionarily diverse plant species. Our comprehensive genome-wide analysis enabled refining EAR motifs as comprising either LxLxL or DLNxxP. Comparing the representation of these sequence signatures in TRs to that of other repressor motifs we show that the EAR motif is the one most frequently represented, detected in 10 to 25% of the TRs from diverse plant species. The mechanisms involved in regulation of EAR motif function and the cellular fates of EAR repressors are currently not well understood. Our earlier analysis had implicated amino acid residues flanking the EAR motifs in regulation of their functionality. Here, we present additional evidence supporting possible regulation of EAR motif function by phosphorylation of integral or adjacent Ser and/or Thr residues. Additionally, we discuss potential novel roles of EAR motifs in plant-pathogen interaction and processes other than transcriptional repression.

  18. Synchronization patterns: from network motifs to hierarchical networks

    NASA Astrophysics Data System (ADS)

    Krishnagopal, Sanjukta; Lehnert, Judith; Poel, Winnie; Zakharova, Anna; Schöll, Eckehard

    2017-03-01

    We investigate complex synchronization patterns such as cluster synchronization and partial amplitude death in networks of coupled Stuart-Landau oscillators with fractal connectivities. The study of fractal or self-similar topology is motivated by the network of neurons in the brain. This fractal property is well represented in hierarchical networks, for which we present three different models. In addition, we introduce an analytical eigensolution method and provide a comprehensive picture of the interplay of network topology and the corresponding network dynamics, thus allowing us to predict the dynamics of arbitrarily large hierarchical networks simply by analysing small network motifs. We also show that oscillation death can be induced in these networks, even if the coupling is symmetric, contrary to previous understanding of oscillation death. Our results show that there is a direct correlation between topology and dynamics: hierarchical networks exhibit the corresponding hierarchical dynamics. This helps bridge the gap between mesoscale motifs and macroscopic networks. This article is part of the themed issue 'Horizons of cybernetical physics'.

  19. Prevalent RNA recognition motif duplication in the human genome.

    PubMed

    Tsai, Yihsuan S; Gomez, Shawn M; Wang, Zefeng

    2014-05-01

    The sequence-specific recognition of RNA by proteins is mediated through various RNA binding domains, with the RNA recognition motif (RRM) being the most frequent and present in >50% of RNA-binding proteins (RBPs). Many RBPs contain multiple RRMs, and it is unclear how each RRM contributes to the binding specificity of the entire protein. We found that RRMs within the same RBP (i.e., sibling RRMs) tend to have significantly higher similarity than expected by chance. Sibling RRM pairs from RBPs shared by multiple species tend to have lower similarity than those found only in a single species, suggesting that multiple RRMs within the same protein might arise from domain duplication followed by divergence through random mutations. This finding is exemplified by a recent RRM domain duplication in DAZ proteins and an ancient duplication in PABP proteins. Additionally, we found that different similarities between sibling RRMs are associated with distinct functions of an RBP and that the RBPs tend to contain repetitive sequences with low complexity. Taken together, this study suggests that the number of RBPs with multiple RRMs has expanded in mammals and that the multiple sibling RRMs may recognize similar target motifs in a cooperative manner.

  20. Functional implications of local DNA structures in regulatory motifs.

    PubMed

    Xiang, Qian

    2013-01-01

    The three-dimensional structure of DNA has been proposed to be a major determinant for functional transcription factors (TFs) and DNA interaction. Here, we use hydroxyl radical cleavage pattern as a measure of local DNA structure. We compared the conservation between DNA sequence and structure in terms of information content and attempted to assess the functional implications of DNA structures in regulatory motifs. We used statistical methods to evaluate the structural divergence of substituting a single position within a binding site and applied them to a collection of putative regulatory motifs. The following are our major observations: (i) we observed more information in structural alignment than in the corresponding sequence alignment for most of the transcriptional factors; (ii) for each TF, majority of positions have more information in the structural alignment as compared to the sequence alignment; (iii) we further defined a DNA structural divergence score (SD score) for each wild-type and mutant pair that is distinguished by single-base mutation. The SD score for benign mutations is significantly lower than that of switch mutations. This indicates structural conservation is also important for TFBS to be functional and DNA structures will provide previously unappreciated information for TF to realize the binding specificity.

  1. Applying Side-chain Flexibility in Motifs for Protein Docking

    PubMed Central

    Liu, Hui; Lin, Feng; Yang, Jian-Li; Wang, Hong-Rui; Liu, Xiu-Ling

    2015-01-01

    Conventional rigid docking algorithms have been unsatisfactory in their computational results, largely due to the fact that protein structures are flexible in live environments. In response, we propose to introduce the side-chain flexibility in protein motif into the docking. First, the Morse theory is applied to curvature labeling and surface region growing, for segmentation of the protein surface into smaller patches. Then, the protein is described by an ensemble of conformations that incorporate the flexibility of interface side chains and are sampled using rotamers. Next, a 3D rotation invariant shape descriptor is proposed to deal with the flexible motifs and surface patches; thus, pairwise complementarity matching is needed only between the convex patches of ligand and the concave patches of receptor. The iterative closest point (ICP) algorithm is implemented for geometric alignment of the two 3D protein surface patches. Compared with the fast Fourier transform-based global geometric matching algorithm and other methods, our FlexDock system generates much less false-positive docking results, which benefits identification of the complementary candidates. Our computational experiments show the advantages of the proposed flexible docking algorithm over its counterparts. PMID:26508871

  2. Identifying DNA Binding Motifs by Combining Data from Different Sources

    SciTech Connect

    Mao, Linyong; Resat, Haluk; Nagib Callaos; Katsuhisa Horimoto; Jake Chen; Amy Sze Chan

    2004-07-19

    A transcription factor regulates the expression of its target genes by binding to their operator regions. It functions by affecting the interactions between RNA polymerases and the gene's promoter. Many transcription factors bind to their targets by recognizing a specific DNA sequence pattern, which is referred to as a consensus sequence or a motif. Since it would remove the possible biases, combining biological data from different sources can be expected to improve the quality of the information extracted from the biological data. We analyzed the microarray gene expression data and the organism's genome sequence jointly to determine the transcription factor recognition sequences with more accuracy. Utilizing such a data integration approach, we have investigated the regulation of the photosynthesis genes of the purple non-sulphur photosynthetic bacterium Rhodobacter sphaeroides. The photosynthesis genes in this organism are tightly regulated as a function of environmental growth conditions by three major regulatory systems, PrrB/PrrA, AppA/PpsR and FnrL. In this study, we have detected a previously undefined PrrA consensus sequence, improved the previously known DNA-binding motif of PpsR, and confirmed the consensus sequence of the global regulator FnrL.

  3. Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases

    PubMed Central

    Zhao, Bryan M.; Keasey, Sarah L.; Tropea, Joseph E.; Lountos, George T.; Dyas, Beverly K.; Cherry, Scott; Raran-Kurussi, Sreejith; Waugh, David S.; Ulrich, Robert G.

    2015-01-01

    Protein tyrosine phosphatases dephosphorylate tyrosine residues of proteins, whereas, dual specificity phosphatases (DUSPs) are a subgroup of protein tyrosine phosphatases that dephosphorylate not only Tyr(P) residue, but also the Ser(P) and Thr(P) residues of proteins. The DUSPs are linked to the regulation of many cellular functions and signaling pathways. Though many cellular targets of DUSPs are known, the relationship between catalytic activity and substrate specificity is poorly defined. We investigated the interactions of peptide substrates with select DUSPs of four types: MAP kinases (DUSP1 and DUSP7), atypical (DUSP3, DUSP14, DUSP22 and DUSP27), viral (variola VH1), and Cdc25 (A-C). Phosphatase recognition sites were experimentally determined by measuring dephosphorylation of 6,218 microarrayed Tyr(P) peptides representing confirmed and theoretical phosphorylation motifs from the cellular proteome. A broad continuum of dephosphorylation was observed across the microarrayed peptide substrates for all phosphatases, suggesting a complex relationship between substrate sequence recognition and optimal activity. Further analysis of peptide dephosphorylation by hierarchical clustering indicated that DUSPs could be organized by substrate sequence motifs, and peptide-specificities by phylogenetic relationships among the catalytic domains. The most highly dephosphorylated peptides represented proteins from 29 cell-signaling pathways, greatly expanding the list of potential targets of DUSPs. These newly identified DUSP substrates will be important for examining structure-activity relationships with physiologically relevant targets. PMID:26302245

  4. Discovering interacting domains and motifs in protein-protein interactions.

    PubMed

    Hugo, Willy; Sung, Wing-Kin; Ng, See-Kiong

    2013-01-01

    Many important biological processes, such as the signaling pathways, require protein-protein interactions (PPIs) that are designed for fast response to stimuli. These interactions are usually transient, easily formed, and disrupted, yet specific. Many of these transient interactions involve the binding of a protein domain to a short stretch (3-10) of amino acid residues, which can be characterized by a sequence pattern, i.e., a short linear motif (SLiM). We call these interacting domains and motifs domain-SLiM interactions. Existing methods have focused on discovering SLiMs in the interacting proteins' sequence data. With the recent increase in protein structures, we have a new opportunity to detect SLiMs directly from the proteins' 3D structures instead of their linear sequences. In this chapter, we describe a computational method called SLiMDIet to directly detect SLiMs on domain interfaces extracted from 3D structures of PPIs. SLiMDIet comprises two steps: (1) interaction interfaces belonging to the same domain are extracted and grouped together using structural clustering and (2) the extracted interaction interfaces in each cluster are structurally aligned to extract the corresponding SLiM. Using SLiMDIet, de novo SLiMs interacting with protein domains can be computationally detected from structurally clustered domain-SLiM interactions for PFAM domains which have available 3D structures in the PDB database.

  5. Synchronization patterns: from network motifs to hierarchical networks.

    PubMed

    Krishnagopal, Sanjukta; Lehnert, Judith; Poel, Winnie; Zakharova, Anna; Schöll, Eckehard

    2017-03-06

    We investigate complex synchronization patterns such as cluster synchronization and partial amplitude death in networks of coupled Stuart-Landau oscillators with fractal connectivities. The study of fractal or self-similar topology is motivated by the network of neurons in the brain. This fractal property is well represented in hierarchical networks, for which we present three different models. In addition, we introduce an analytical eigensolution method and provide a comprehensive picture of the interplay of network topology and the corresponding network dynamics, thus allowing us to predict the dynamics of arbitrarily large hierarchical networks simply by analysing small network motifs. We also show that oscillation death can be induced in these networks, even if the coupling is symmetric, contrary to previous understanding of oscillation death. Our results show that there is a direct correlation between topology and dynamics: hierarchical networks exhibit the corresponding hierarchical dynamics. This helps bridge the gap between mesoscale motifs and macroscopic networks.This article is part of the themed issue 'Horizons of cybernetical physics'.

  6. Computational definition of sequence motifs governing constitutive exon splicing.

    PubMed

    Zhang, Xiang H-F; Chasin, Lawrence A

    2004-06-01

    We have searched for sequence motifs that contribute to the recognition of human pre-mRNA splice sites by comparing the frequency of 8-mers in internal noncoding exons versus unspliced pseudo exons and 5' untranslated regions (5' untranslated regions [UTRs]) of transcripts of intronless genes. This type of comparison avoids the isolation of sequences that are distinguished by their protein-coding information. We classified sequence families comprising 2069 putative exonic enhancers and 974 putative exonic silencers. Representatives of each class functioned as enhancers or silencers when inserted into a test exon and assayed in transfected mammalian cells. As a class, the enhancer sequencers were more prevalent and the silencer elements less prevalent in all exons compared with introns. A survey of 58 reported exonic splicing mutations showed good agreement between the splicing phenotype and the effect of the mutation on the motifs defined here. The large number of effective sequences implied by these results suggests that sequences that influence splicing may be very abundant in pre-mRNA.

  7. The helix bundle: A reversible lipid binding motif

    PubMed Central

    Narayanaswami, Vasanthy; Kiss, Robert S.; Weers, Paul M.M.

    2009-01-01

    Apolipoproteins are the protein components of lipoproteins that have the innate ability to inter convert between a lipid-free and a lipid-bound form in a facile manner, a remarkable property conferred by the helix bundle motif. Composed of a series of four or five amphipathic α-helices that fold to form a helix bundle, this motif allows the en face orientation of the hydrophobic faces of the α-helices in the protein interior in the lipid-free state. A conformational switch then permits helix-helix interactions to be substituted by helix-lipid interactions upon lipid binding interaction. This review compares the apolipoprotein high resolution structures and the factors that trigger this switch in insect apolipophorin III and the mammalian apolipoproteins, apolipoprotein E and apolipoprotein A-I, pointing out the commonalities and key differences in the mode of lipid interaction. Further insights into the lipid bound conformation of apolipoproteins are required to fully understand their functional role under physiological conditions. PMID:19770066

  8. Ultrasensitive response motifs: basic amplifiers in molecular signalling networks

    PubMed Central

    Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.

    2013-01-01

    Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm. PMID:23615029

  9. Recursive Alterations of the Relationship between Simple Membrane Geometry and Insertion of Amphiphilic Motifs

    PubMed Central

    Madsen, Kenneth Lindegaard; Herlo, Rasmus

    2017-01-01

    The shape and composition of a membrane directly regulate the localization, activity, and signaling properties of membrane associated proteins. Proteins that both sense and generate membrane curvature, e.g., through amphiphilic insertion motifs, potentially engage in recursive binding dynamics, where the recruitment of the protein itself changes the properties of the membrane substrate. Simple geometric models of membrane curvature interactions already provide prediction tools for experimental observations, however these models are treating curvature sensing and generation as separated phenomena. Here, we outline a model that applies both geometric and basic thermodynamic considerations. This model allows us to predict the consequences of recursive properties in such interaction schemes and thereby integrate the membrane as a dynamic substrate. We use this combined model to hypothesize the origin and properties of tubular carrier systems observed in cells. Furthermore, we pinpoint the coupling to a membrane reservoir as a factor that influences the membrane curvature sensing and generation properties of local curvatures in the cell in line with classic determinants such as lipid composition and membrane geometry. PMID:28208740

  10. Structural complexity of Dengue virus untranslated regions: cis-acting RNA motifs and pseudoknot interactions modulating functionality of the viral genome

    PubMed Central

    Sztuba-Solinska, Joanna; Teramoto, Tadahisa; Rausch, Jason W.; Shapiro, Bruce A.; Padmanabhan, Radhakrishnan; Le Grice, Stuart F. J.

    2013-01-01

    The Dengue virus (DENV) genome contains multiple cis-acting elements required for translation and replication. Previous studies indicated that a 719-nt subgenomic minigenome (DENV-MINI) is an efficient template for translation and (−) strand RNA synthesis in vitro. We performed a detailed structural analysis of DENV-MINI RNA, combining chemical acylation techniques, Pb2+ ion-induced hydrolysis and site-directed mutagenesis. Our results highlight protein-independent 5′–3′ terminal interactions involving hybridization between recognized cis-acting motifs. Probing analyses identified tandem dumbbell structures (DBs) within the 3′ terminus spaced by single-stranded regions, internal loops and hairpins with embedded GNRA-like motifs. Analysis of conserved motifs and top loops (TLs) of these dumbbells, and their proposed interactions with downstream pseudoknot (PK) regions, predicted an H-type pseudoknot involving TL1 of the 5′ DB and the complementary region, PK2. As disrupting the TL1/PK2 interaction, via ‘flipping’ mutations of PK2, previously attenuated DENV replication, this pseudoknot may participate in regulation of RNA synthesis. Computer modeling implied that this motif might function as autonomous structural/regulatory element. In addition, our studies targeting elements of the 3′ DB and its complementary region PK1 indicated that communication between 5′–3′ terminal regions strongly depends on structure and sequence composition of the 5′ cyclization region. PMID:23531545

  11. A type of nucleotide motif that distinguishes tobamovirus species more efficiently than nucleotide signatures.

    PubMed

    Gibbs, A J; Armstrong, J S; Gibbs, M J

    2004-10-01

    The complete genomic sequences of forty-eight tobamoviruses were classified and found to form at least twelve species clusters. Individual species were not conveniently defined by 'nucleotide signatures' (i.e. strings of one or more nucleotides unique to a taxon) as these were scattered sparsely throughout the genomes and were mostly single nucleotides. By contrast all the species were concisely and uniquely distinguished by short nucleotide motifs consisting of conserved genus-specific sites intercalated with variable sites that provided species-specific combinations of nucleotides (nucleotide combination motifs; NC-motifs). We describe the procedure for finding NC-motifs in a convenient and phylogenetically conserved region of the tobamovirus RNA polymerase gene, the '4404-50 motif'. NC-motifs have been found in other sets of homologous sequences, and are convenient for use in published taxonomic descriptions.

  12. Exhaustive Search for Over-represented DNA Sequence Motifs with CisFinder

    PubMed Central

    Sharov, Alexei A.; Ko, Minoru S.H.

    2009-01-01

    We present CisFinder software, which generates a comprehensive list of motifs enriched in a set of DNA sequences and describes them with position frequency matrices (PFMs). A new algorithm was designed to estimate PFMs directly from counts of n-mer words with and without gaps; then PFMs are extended over gaps and flanking regions and clustered to generate non-redundant sets of motifs. The algorithm successfully identified binding motifs for 12 transcription factors (TFs) in embryonic stem cells based on published chromatin immunoprecipitation sequencing data. Furthermore, CisFinder successfully identified alternative binding motifs of TFs (e.g. POU5F1, ESRRB, and CTCF) and motifs for known and unknown co-factors of genes associated with the pluripotent state of ES cells. CisFinder also showed robust performance in the identification of motifs that were only slightly enriched in a set of DNA sequences. PMID:19740934

  13. Mining bridge and brick motifs from complex biological networks for functionally and statistically significant discovery.

    PubMed

    Cheng, Chia-Ying; Huang, Chung-Yuan; Sun, Chuen-Tsai

    2008-02-01

    A major task for postgenomic systems biology researchers is to systematically catalogue molecules and their interactions within living cells. Advancements in complex-network theory are being made toward uncovering organizing principles that govern cell formation and evolution, but we lack understanding of how molecules and their interactions determine how complex systems function. Molecular bridge motifs include isolated motifs that neither interact nor overlap with others, whereas brick motifs act as network foundations that play a central role in defining global topological organization. To emphasize their structural organizing and evolutionary characteristics, we define bridge motifs as consisting of weak links only and brick motifs as consisting of strong links only, then propose a method for performing two tasks simultaneously, which are as follows: 1) detecting global statistical features and local connection structures in biological networks and 2) locating functionally and statistically significant network motifs. To further understand the role of biological networks in system contexts, we examine functional and topological differences between bridge and brick motifs for predicting biological network behaviors and functions. After observing brick motif similarities between E. coli and S. cerevisiae, we note that bridge motifs differentiate C. elegans from Drosophila and sea urchin in three types of networks. Similarities (differences) in bridge and brick motifs imply similar (different) key circuit elements in the three organisms. We suggest that motif-content analyses can provide researchers with global and local data for real biological networks and assist in the search for either isolated or functionally and topologically overlapping motifs when investigating and comparing biological system functions and behaviors.

  14. Transcription factor and microRNA-regulated network motifs for cancer and signal transduction networks

    PubMed Central

    2015-01-01

    Abstract Background Molecular networks are the basis of biological processes. Such networks can be decomposed into smaller modules, also known as network motifs. These motifs show interesting dynamical behaviors, in which co-operativity effects between the motif components play a critical role in human diseases. We have developed a motif-searching algorithm, which is able to identify common motif types from the cancer networks and signal transduction networks (STNs). Some of the network motifs are interconnected which can be merged together and form more complex structures, the so-called coupled motif structures (CMS). These structures exhibit mixed dynamical behavior, which may lead biological organisms to perform specific functions. Results In this study, we integrate transcription factors (TFs), microRNAs (miRNAs), miRNA targets and network motifs information to build the cancer-related TF-miRNA-motif networks (TMMN). This allows us to examine the role of network motifs in cancer formation at different levels of regulation, i.e. transcription initiation (TF → miRNA), gene-gene interaction (CMS), and post-transcriptional regulation (miRNA → target genes). Among the cancer networks and STNs we considered, it is found that there is a substantial amount of crosstalking through motif interconnections, in particular, the crosstalk between prostate cancer network and PI3K-Akt STN. Conclusions To validate the role of network motifs in cancer formation, several examples are presented which demonstrated the effectiveness of the present approach. A web-based platform has been set up which can be accessed at: http://ppi.bioinfo.asia.edu.tw/pathway/. It is very likely that our results can supply very specific CMS missing information for certain cancer types, it is an indispensable tool for cancer biology research. PMID:25707690

  15. Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages

    PubMed Central

    2011-01-01

    Background Deficiency of the transcription factor MafB, which is normally expressed in macrophages, can underlie cellular dysfunction associated with a range of autoimmune diseases and arteriosclerosis. MafB has important roles in cell differentiation and regulation of target gene expression; however, the mechanisms of this regulation and the identities of other transcription factors with which MafB interacts remain uncertain. Bioinformatics methods provide a valuable approach for elucidating the nature of these interactions with transcriptional regulatory elements from a large number of DNA sequences. In particular, identification of patterns of co-occurrence of regulatory cis-elements (motifs) offers a robust approach. Results Here, the directional relationships among several functional motifs were evaluated using the Log-linear Graphical Model (LGM) after extraction and search for evolutionarily conserved motifs. This analysis highlighted GATA-1 motifs and 5’AT-rich half Maf recognition elements (MAREs) in promoter regions of 18 genes that were down-regulated in Mafb deficient macrophages. GATA-1 motifs and MafB motifs could regulate expression of these genes in both a negative and positive manner, respectively. The validity of this conclusion was tested with data from a luciferase assay that used a C1qa promoter construct carrying both the GATA-1 motifs and MAREs. GATA-1 was found to inhibit the activity of the C1qa promoter with the GATA-1 motifs and MafB motifs. Conclusions These observations suggest that both the GATA-1 motifs and MafB motifs are important for lineage specific expression of C1qa. In addition, these findings show that analysis of combinations of evolutionarily conserved motifs can be successfully used to identify patterns of gene regulation. PMID:22784578

  16. RNAMotifScanX: a graph alignment approach for RNA structural motif identification.

    PubMed

    Zhong, Cuncong; Zhang, Shaojie

    2015-03-01

    RNA structural motifs are recurrent three-dimensional (3D) components found in the RNA architecture. These RNA structural motifs play important structural or functional roles and usually exhibit highly conserved 3D geometries and base-interaction patterns. Analysis of the RNA 3D structures and elucidation of their molecular functions heavily rely on efficient and accurate identification of these motifs. However, efficient RNA structural motif search tools are lacking due to the high complexity of these motifs. In this work, we present RNAMotifScanX, a motif search tool based on a base-interaction graph alignment algorithm. This novel algorithm enables automatic identification of both partially and fully matched motif instances. RNAMotifScanX considers noncanonical base-pairing interactions, base-stacking interactions, and sequence conservation of the motifs, which leads to significantly improved sensitivity and specificity as compared with other state-of-the-art search tools. RNAMotifScanX also adopts a carefully designed branch-and-bound technique, which enables ultra-fast search of large kink-turn motifs against a 23S rRNA. The software package RNAMotifScanX is implemented using GNU C++, and is freely available from http://genome.ucf.edu/RNAMotifScanX.

  17. Analysis of Genomic Sequence Motifs for Deciphering Transcription Factor Binding and Transcriptional Regulation in Eukaryotic Cells

    PubMed Central

    Boeva, Valentina

    2016-01-01

    Eukaryotic genomes contain a variety of structured patterns: repetitive elements, binding sites of DNA and RNA associated proteins, splice sites, and so on. Often, these structured patterns can be formalized as motifs and described using a proper mathematical model such as position weight matrix and IUPAC consensus. Two key tasks are typically carried out for motifs in the context of the analysis of genomic sequences. These are: identification in a set of DNA regions of over-represented motifs from a particular motif database, and de novo discovery of over-represented motifs. Here we describe existing methodology to perform these two tasks for motifs characterizing transcription factor binding. When applied to the output of ChIP-seq and ChIP-exo experiments, or to promoter regions of co-modulated genes, motif analysis techniques allow for the prediction of transcription factor binding events and enable identification of transcriptional regulators and co-regulators. The usefulness of motif analysis is further exemplified in this review by how motif discovery improves peak calling in ChIP-seq and ChIP-exo experiments and, when coupled with information on gene expression, allows insights into physical mechanisms of transcriptional modulation. PMID:26941778

  18. WordSpy: identifying transcription factor binding motifs by building a dictionary and learning a grammar

    PubMed Central

    Wang, Guandong; Yu, Taotao; Zhang, Weixiong

    2005-01-01

    Transcription factor (TF) binding sites or motifs (TFBMs) are functional cis-regulatory DNA sequences that play an essential role in gene transcriptional regulation. Although many experimental and computational methods have been developed, finding TFBMs remains a challenging problem. We propose and develop a novel dictionary based motif finding algorithm, which we call WordSpy. One significant feature of WordSpy is the combination of a word counting method and a statistical model which consists of a dictionary of motifs and a grammar specifying their usage. The algorithm is suitable for genome-wide motif finding; it is capable of discovering hundreds of motifs from a large set of promoters in a single run. We further enhance WordSpy by applying gene expression information to separate true TFBMs from spurious ones, and by incorporating negative sequences to identify discriminative motifs. In addition, we also use randomly selected promoters from the genome to evaluate the significance of the discovered motifs. The output from WordSpy consists of an ordered list of putative motifs and a set of regulatory sequences with motif binding sites highlighted. The web server of WordSpy is available at . PMID:15980501

  19. Methods and compositions for targeting macromolecules into the nucleus

    SciTech Connect

    Chook, Yuh Min

    2013-06-25

    The present invention includes compositions, methods and kits for directing an agent across the nuclear membrane of a cell. The present invention includes a Karyopherin beta2 translocation motif in a polypeptide having a slightly positively charged region or a slightly hydrophobic region and one or more R/K/H-X.sub.(2-5)-P-Y motifs. The polypeptide targets the agent into the cell nucleus.

  20. cisExpress: motif detection in DNA sequences

    PubMed Central

    Triska, Martin; Grocutt, David; Southern, James; Murphy, Denis J.; Tatarinova, Tatiana

    2013-01-01

    Motivation: One of the major challenges for contemporary bioinformatics is the analysis and accurate annotation of genomic datasets to enable extraction of useful information about the functional role of DNA sequences. This article describes a novel genome-wide statistical approach to the detection of specific DNA sequence motifs based on similarities between the promoters of similarly expressed genes. This new tool, cisExpress, is especially designed for use with large datasets, such as those generated by publicly accessible whole genome and transcriptome projects. cisExpress uses a task farming algorithm to exploit all available computational cores within a shared memory node. We demonstrate the robust nature and validity of the proposed method. It is applicable for use with a wide range of genomic databases for any species of interest. Availability: cisExpress is available at www.cisexpress.org. Contact: tatiana.tatarinova@usc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23793750

  1. Bacteria-mimicking nanoparticle surface functionalization with targeting motifs

    NASA Astrophysics Data System (ADS)

    Lai, Mei-Hsiu; Clay, Nicholas E.; Kim, Dong Hyun; Kong, Hyunjoon

    2015-04-01

    In recent years, surface modification of nanocarriers with targeting motifs has been explored to modulate delivery of various diagnostic, sensing and therapeutic molecular cargo to desired sites of interest in in vitro bioengineering platforms and in vivo pathologic tissue. However, most surface functionalization approaches are often plagued by complex chemical modifications and effortful purifications. To resolve such challenges, this study demonstrates a unique method to immobilize antibodies that can act as targeting motifs on the surfaces of nanocarriers, inspired by a process that bacteria use for immobilization of the host's antibodies. We hypothesized that alkylated Staphylococcus aureus protein A (SpA) would self-assemble with micelles and subsequently induce stable coupling of antibodies to the micelles. We examined this hypothesis by using poly(2-hydroxyethyl-co-octadecyl aspartamide) (PHEA-g-C18) as a model polymer to form micelles. The self-assembly between the micelles and alkylated SpA became more thermodynamically favorable by increasing the degree of substitution of octadecyl chains to PHEA-g-C18, due to a positive entropy change. Lastly, the mixing of SpA-PA-coupled micelles with antibodies resulted in the coating of micelles with antibodies, as confirmed with a fluorescence resonance energy transfer (FRET) assay. The micelles coated with antibodies to VCAM-1 or integrin αv displayed a higher binding affinity to substrates coated with VCAM-1 and integrin αvβ3, respectively, than other controls, as evaluated with surface plasmon resonance (SPR) spectroscopy and a circulation-simulating flow chamber. We envisage that this bacteria-inspired protein immobilization approach will be useful to improve the quality of targeted delivery of nanoparticles, and can be extended to modify the surface of a wide array of nanocarriers.In recent years, surface modification of nanocarriers with targeting motifs has been explored to modulate delivery of various

  2. Sulfur-induced structural motifs on copper and gold surfaces

    SciTech Connect

    Walen, Holly

    2016-01-01

    The interaction of sulfur with copper and gold surfaces plays a fundamental role in important phenomena that include coarsening of surface nanostructures, and self-assembly of alkanethiols. Here, we identify and analyze unique sulfur-induced structural motifs observed on the low-index surfaces of these two metals. We seek out these structures in an effort to better understand the fundamental interactions between these metals and sulfur that lends to the stability and favorability of metal-sulfur complexes vs. chemisorbed atomic sulfur. The experimental observations presented here—made under identical conditions—together with extensive DFT analyses, allow comparisons and insights into factors that favor the existence of metal-sulfur complexes, vs. chemisorbed atomic sulfur, on metal terraces. We believe this data will be instrumental in better understanding the complex phenomena occurring between the surfaces of coinage metals and sulfur.

  3. RNA Sociology: Group Behavioral Motifs of RNA Consortia

    PubMed Central

    Witzany, Guenther

    2014-01-01

    RNA sociology investigates the behavioral motifs of RNA consortia from the social science perspective. Besides the self-folding of RNAs into single stem loop structures, group building of such stem loops results in a variety of essential agents that are highly active in regulatory processes in cellular and non-cellular life. RNA stem loop self-folding and group building do not depend solely on sequence syntax; more important are their contextual (functional) needs. Also, evolutionary processes seem to occur through RNA stem loop consortia that may act as a complement. This means the whole entity functions only if all participating parts are coordinated, although the complementary building parts originally evolved for different functions. If complementary groups, such as rRNAs and tRNAs, are placed together in selective pressure contexts, new evolutionary features may emerge. Evolution initiated by competent agents in natural genome editing clearly contrasts with statistical error replication narratives. PMID:25426799

  4. Study on online community user motif using web usage mining

    NASA Astrophysics Data System (ADS)

    Alphy, Meera; Sharma, Ajay

    2016-04-01

    The Web usage mining is the application of data mining, which is used to extract useful information from the online community. The World Wide Web contains at least 4.73 billion pages according to Indexed Web and it contains at least 228.52 million pages according Dutch Indexed web on 6th august 2015, Thursday. It’s difficult to get needed data from these billions of web pages in World Wide Web. Here is the importance of web usage mining. Personalizing the search engine helps the web user to identify the most used data in an easy way. It reduces the time consumption; automatic site search and automatic restore the useful sites. This study represents the old techniques to latest techniques used in pattern discovery and analysis in web usage mining from 1996 to 2015. Analyzing user motif helps in the improvement of business, e-commerce, personalisation and improvement of websites.

  5. Sequential dynamics in the motif of excitatory coupled elements

    NASA Astrophysics Data System (ADS)

    Korotkov, Alexander G.; Kazakov, Alexey O.; Osipov, Grigory V.

    2015-11-01

    In this article a new model of motif (small ensemble) of neuron-like elements is proposed. It is built with the use of the generalized Lotka-Volterra model with excitatory couplings. The main motivation for this work comes from the problems of neuroscience where excitatory couplings are proved to be the predominant type of interaction between neurons of the brain. In this paper it is shown that there are two modes depending on the type of coupling between the elements: the mode with a stable heteroclinic cycle and the mode with a stable limit cycle. Our second goal is to examine the chaotic dynamics of the generalized three-dimensional Lotka-Volterra model.

  6. Polyproline and triple helix motifs in host-pathogen recognition.

    PubMed

    Berisio, Rita; Vitagliano, Luigi

    2012-12-01

    Secondary structure elements often mediate protein-protein interactions. Despite their low abundance in folded proteins, polyproline II (PPII) and its variant, the triple helix, are frequently involved in protein-protein interactions, likely due to their peculiar propensity to be solvent-exposed. We here review the role of PPII and triple helix in mediating hostpathogen interactions, with a particular emphasis to the structural aspects of these processes. After a brief description of the basic structural features of these elements, examples of host-pathogen interactions involving these motifs are illustrated. Literature data suggest that the role played by PPII motif in these processes is twofold. Indeed, PPII regions may directly mediate interactions between proteins of the host and the pathogen. Alternatively, PPII may act as structural spacers needed for the correct positioning of the elements needed for adhesion and infectivity. Recent investigations have highlighted that collagen triple helix is also a common target for bacterial adhesins. Although structural data on complexes between adhesins and collagen models are rather limited, experimental and theoretical studies have unveiled some interesting clues of the recognition process. Interestingly, very recent data show that not only is the triple helix used by pathogens as a target in the host-pathogen interaction but it may also act as a bait in these processes since bacterial proteins containing triple helix regions have been shown to interact with host proteins. As both PPII and triple helix expose several main chain non-satisfied hydrogen bond acceptors and donors, both elements are highly solvated. The preservation of the solvation state of both PPII and triple helix upon protein-protein interaction is an emerging aspect that will be here thoroughly discussed.

  7. Multivalent dendrimer vectors with DNA intercalation motifs for gene delivery.

    PubMed

    Wong, Pamela T; Tang, Kenny; Coulter, Alexa; Tang, Shengzhuang; Baker, James R; Choi, Seok Ki

    2014-11-10

    Poly(amido amine) (PAMAM) dendrimers constitute an important class of nonviral, cationic vectors in gene delivery. Here we report on a new concept for dendrimer vector design based on the incorporation of dual binding motifs: DNA intercalation, and receptor recognition for targeted delivery. We prepared a series of dendrimer conjugates derived from a fifth generation (G5) PAMAM dendrimer, each conjugated with multiple folate (FA) or riboflavin (RF) ligands for cell receptor targeting, and with 3,8-diamino-6-phenylphenanthridinium ("DAPP")-derived ligands for anchoring a DNA payload. Polyplexes of each dendrimer with calf thymus dsDNA were made and characterized by surface plasmon resonance (SPR) spectroscopy, dynamic light scattering (DLS) and zeta potential measurement. These studies provided evidence supporting polyplex formation based on the observation of tight DNA-dendrimer adhesion, and changes in particle size and surface charge upon coincubation. Further SPR studies to investigate the adhesion of the polyplex to a model surface immobilized with folate binding protein (FBP), demonstrated that the DNA payload has only a minimal effect on the receptor binding activity of the polyplex: KD = 0.22 nM for G5(FA)(DAPP) versus 0.98 nM for its polyplex. Finally, we performed in vitro transfection assays to determine the efficiency of conjugate mediated delivery of a luciferase-encoding plasmid into the KB cancer cell line and showed that RF-conjugated dendrimers were 1 to 2 orders of magnitude more effective in enhancing luciferase gene transfection than a plasmid only control. In summary, this study serves as a proof of concept for DNA-ligand intercalation as a motif in the design of multivalent dendrimer vectors for targeted gene delivery.

  8. Improved K-means clustering algorithm for exploring local protein sequence motifs representing common structural property.

    PubMed

    Zhong, Wei; Altun, Gulsah; Harrison, Robert; Tai, Phang C; Pan, Yi

    2005-09-01

    Information about local protein sequence motifs is very important to the analysis of biologically significant conserved regions of protein sequences. These conserved regions can potentially determine the diverse conformation and activities of proteins. In this work, recurring sequence motifs of proteins are explored with an improved K-means clustering algorithm on a new dataset. The structural similarity of these recurring sequence clusters to produce sequence motifs is studied in order to evaluate the relationship between sequence motifs and their structures. To the best of our knowledge, the dataset used by our research is the most updated dataset among similar studies for sequence motifs. A new greedy initialization method for the K-means algorithm is proposed to improve traditional K-means clustering techniques. The new initialization method tries to choose suitable initial points, which are well separated and have the potential to form high-quality clusters. Our experiments indicate that the improved K-means algorithm satisfactorily increases the percentage of sequence segments belonging to clusters with high structural similarity. Careful comparison of sequence motifs obtained by the improved and traditional algorithms also suggests that the improved K-means clustering algorithm may discover some relatively weak and subtle sequence motifs, which are undetectable by the traditional K-means algorithms. Many biochemical tests reported in the literature show that these sequence motifs are biologically meaningful. Experimental results also indicate that the improved K-means algorithm generates more detailed sequence motifs representing common structures than previous research. Furthermore, these motifs are universally conserved sequence patterns across protein families, overcoming some weak points of other popular sequence motifs. The satisfactory result of the experiment suggests that this new K-means algorithm may be applied to other areas of bioinformatics

  9. Assembly of supramolecular DNA complexes containing both G-quadruplexes and i-motifs by enhancing the G-repeat-bearing capacity of i-motifs

    PubMed Central

    Cao, Yanwei; Gao, Shang; Yan, Yuting; Bruist, Michael F.; Wang, Bing; Guo, Xinhua

    2017-01-01

    The single-step assembly of supramolecular complexes containing both i-motifs and G-quadruplexes (G4s) is demonstrated. This can be achieved because the formation of four-stranded i-motifs appears to be little affected by certain terminal residues: a five-cytosine tetrameric i-motif can bear ten-base flanking residues. However, things become complex when different lengths of guanine-repeats are added at the 3′ or 5′ ends of the cytosine-repeats. Here, a series of oligomers d(XGiXC5X) and d(XC5XGiX) (X = A, T or none; i < 5) are designed to study the impact of G-repeats on the formation of tetrameric i-motifs. Our data demonstrate that tetramolecular i-motif structure can tolerate specific flanking G-repeats. Assemblies of these oligonucleotides are polymorphic, but may be controlled by solution pH and counter ion species. Importantly, we find that the sequences d(TGiAC5) can form the tetrameric i-motif in large quantities. This leads to the design of two oligonucleotides d(TG4AC7) and d(TGBrGGBrGAC7) that self-assemble to form quadruplex supramolecules under certain conditions. d(TG4AC7) forms supramolecules under acidic conditions in the presence of K+ that are mainly V-shaped or ring-like containing parallel G4s and antiparallel i-motifs. d(TGBrGGBrGAC7) forms long linear quadruplex wires under acidic conditions in the presence of Na+ that consist of both antiparallel G4s and i-motifs. PMID:27899568

  10. Wayward Warriors: The Viking Motif in Swedish and English Children's Literature

    ERIC Educational Resources Information Center

    Sundmark, Björn

    2014-01-01

    In this article the Viking motif in children's literature is explored--from its roots in (adult) nationalist and antiquarian discourse, over pedagogical and historical texts for children, to the eventual diversification (or dissolution) of the motif into different genres and forms. The focus is on Swedish Viking narratives, but points of…

  11. Base motif recognition and design of DNA templates for fluorescent silver clusters by machine learning.

    PubMed

    Copp, Stacy M; Bogdanov, Petko; Debord, Mark; Singh, Ambuj; Gwinn, Elisabeth

    2014-09-03

    Discriminative base motifs within DNA templates for fluorescent silver clusters are identified using methods that combine large experimental data sets with machine learning tools for pattern recognition. Combining the discovery of certain multibase motifs important for determining fluorescence brightness with a generative algorithm, the probability of selecting DNA templates that stabilize fluorescent silver clusters is increased by a factor of >3.

  12. Bayesian multiple-instance motif discovery with BAMBI: inference of recombinase and transcription factor binding sites

    PubMed Central

    Jajamovich, Guido H.; Wang, Xiaodong; Arkin, Adam P.; Samoilov, Michael S.

    2011-01-01

    Finding conserved motifs in genomic sequences represents one of essential bioinformatic problems. However, achieving high discovery performance without imposing substantial auxiliary constraints on possible motif features remains a key algorithmic challenge. This work describes BAMBI—a sequential Monte Carlo motif-identification algorithm, which is based on a position weight matrix model that does not require additional constraints and is able to estimate such motif properties as length, logo, number of instances and their locations solely on the basis of primary nucleotide sequence data. Furthermore, should biologically meaningful information about motif attributes be available, BAMBI takes advantage of this knowledge to further refine the discovery results. In practical applications, we show that the proposed approach can be used to find sites of such diverse DNA-binding molecules as the cAMP receptor protein (CRP) and Din-family site-specific serine recombinases. Results obtained by BAMBI in these and other settings demonstrate better statistical performance than any of the four widely-used profile-based motif discovery methods: MEME, BioProspector with BioOptimizer, SeSiMCMC and Motif Sampler as measured by the nucleotide-level correlation coefficient. Additionally, in the case of Din-family recombinase target site discovery, the BAMBI-inferred motif is found to be the only one functionally accurate from the underlying biochemical mechanism standpoint. C++ and Matlab code is available at http://www.ee.columbia.edu/~guido/BAMBI or http://genomics.lbl.gov/BAMBI/. PMID:21948794

  13. Physical-chemical property based sequence motifs and methods regarding same

    DOEpatents

    Braun, Werner; Mathura, Venkatarajan S.; Schein, Catherine H.

    2008-09-09

    A data analysis system, program, and/or method, e.g., a data mining/data exploration method, using physical-chemical property motifs. For example, a sequence database may be searched for identifying segments thereof having physical-chemical properties similar to the physical-chemical property motifs.

  14. Computational generation and screening of RNA motifs in large nucleotide sequence pools

    PubMed Central

    Kim, Namhee; Izzo, Joseph A.; Elmetwaly, Shereef; Gan, Hin Hark; Schlick, Tamar

    2010-01-01

    Although identification of active motifs in large random sequence pools is central to RNA in vitro selection, no systematic computational equivalent of this process has yet been developed. We develop a computational approach that combines target pool generation, motif scanning and motif screening using secondary structure analysis for applications to 1012–1014-sequence pools; large pool sizes are made possible using program redesign and supercomputing resources. We use the new protocol to search for aptamer and ribozyme motifs in pools up to experimental pool size (1014 sequences). We show that motif scanning, structure matching and flanking sequence analysis, respectively, reduce the initial sequence pool by 6–8, 1–2 and 1 orders of magnitude, consistent with the rare occurrence of active motifs in random pools. The final yields match the theoretical yields from probability theory for simple motifs and overestimate experimental yields, which constitute lower bounds, for aptamers because screening analyses beyond secondary structure information are not considered systematically. We also show that designed pools using our nucleotide transition probability matrices can produce higher yields for RNA ligase motifs than random pools. Our methods for generating, analyzing and designing large pools can help improve RNA design via simulation of aspects of in vitro selection. PMID:20448026

  15. The PXDLS linear motif regulates circadian rhythmicity through protein–protein interactions

    PubMed Central

    Shalev, Moran; Aviram, Rona; Adamovich, Yaarit; Kraut-Cohen, Judith; Shamia, Tal; Ben-Dor, Shifra; Golik, Marina; Asher, Gad

    2014-01-01

    The circadian core clock circuitry relies on interlocked transcription-translation feedback loops that largely count on multiple protein interactions. The molecular mechanisms implicated in the assembly of these protein complexes are relatively unknown. Our bioinformatics analysis of short linear motifs, implicated in protein interactions, reveals an enrichment of the Pro-X-Asp-Leu-Ser (PXDLS) motif within circadian transcripts. We show that the PXDLS motif can bind to BMAL1/CLOCK and disrupt circadian oscillations in a cell-autonomous manner. Remarkably, the motif is evolutionary conserved in the core clock protein REV-ERBα, and additional proteins implicated in the clock's function (NRIP1, CBP). In this conjuncture, we uncover a novel cross talk between the two principal core clock feedback loops and show that BMAL/CLOCK and REV-ERBα interact and that the PXDLS motif of REV-ERBα participates in their binding. Furthermore, we demonstrate that the PXDLS motifs of NRIP1 and CBP are involved in circadian rhythmicity. Our findings suggest that the PXDLS motif plays an important role in circadian rhythmicity through regulation of protein interactions within the clock circuitry and that short linear motifs can be employed to modulate circadian oscillations. PMID:25260595

  16. Population genomics and transcriptional consequences of regulatory motif variation in globally diverse Saccharomyces cerevisiae strains.

    PubMed

    Connelly, Caitlin F; Skelly, Daniel A; Dunham, Maitreya J; Akey, Joshua M

    2013-07-01

    Noncoding genetic variation is known to significantly influence gene expression levels in a growing number of specific cases; however, the patterns of genome-wide noncoding variation present within populations, the evolutionary forces acting on noncoding variants, and the relative effects of regulatory polymorphisms on transcript abundance are not well characterized. Here, we address these questions by analyzing patterns of regulatory variation in motifs for 177 DNA binding proteins in 37 strains of Saccharomyces cerevisiae. Between S. cerevisiae strains, we found considerable polymorphism in regulatory motifs across strains (mean π = 0.005) as well as diversity in regulatory motifs (mean 0.91 motifs differences per regulatory region). Population genetics analyses reveal that motifs are under purifying selection, and there is considerable heterogeneity in the magnitude of selection across different motifs. Finally, we obtained RNA-Seq data in 22 strains and identified 49 polymorphic DNA sequence motifs in 30 distinct genes that are significantly associated with transcriptional differences between strains. In 22 of these genes, there was a single polymorphic motif associated with expression in the upstream region. Our results provide comprehensive insights into the evolutionary trajectory of regulatory variation in yeast and the characteristics of a compendium of regulatory alleles.

  17. Redemptive Rhetoric: The Continuity Motif in the Rhetoric of Right to Life.

    ERIC Educational Resources Information Center

    Solomon, Martha

    1980-01-01

    Traces the use of the "continuity" motif in the Right to Life movement's rhetoric and its influence on the depiction of the abortion controversy. Analyzes how the motif functions rhetorically to aid the movement in defining its activities and involvement. (PD)

  18. Neutral red as a specific light-up fluorescent probe for i-motif DNA.

    PubMed

    Xu, Lijun; Wang, Jine; Sun, Na; Liu, Min; Cao, Yi; Wang, Zhili; Pei, Renjun

    2016-12-06

    We report a specific light-up fluorescent probe for i-motif DNA for the first time. Compared with the previously reported probes, neutral red could selectively interact with an i-motif and show a significant increase in its fluorescence. This feature makes it advantageous for designing label-free fluorescent sensing systems.

  19. An Examination of Four Key Motifs Found in High Fantasy for Children.

    ERIC Educational Resources Information Center

    Cohen, John Arthur

    The purpose of this study was to come to a greater understanding of contemporary high fantasy for children by analyzing in depth the nature and functions of four key motifs of this sub-genre of fantasy. These motifs are created worlds, time displacement, quest, and combat between good and evil. The 47 books chosen for analysis were recommended in…

  20. Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated

    PubMed Central

    2010-01-01

    Background DNA methylation can regulate gene expression by modulating the interaction between DNA and proteins or protein complexes. Conserved consensus motifs exist across the human genome ("predicted transcription factor binding sites": "predicted TFBS") but the large majority of these are proven by chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) not to be biological transcription factor binding sites ("empirical TFBS"). We hypothesize that DNA methylation at conserved consensus motifs prevents promiscuous or disorderly transcription factor binding. Results Using genome-wide methylation maps of the human heart and sperm, we found that all conserved consensus motifs as well as the subset of those that reside outside CpG islands have an aggregate profile of hyper-methylation. In contrast, empirical TFBS with conserved consensus motifs have a profile of hypo-methylation. 40% of empirical TFBS with conserved consensus motifs resided in CpG islands whereas only 7% of all conserved consensus motifs were in CpG islands. Finally we further identified a minority subset of TF whose profiles are either hypo-methylated or neutral at their respective conserved consensus motifs implicating that these TF may be responsible for establishing or maintaining an un-methylated DNA state, or whose binding is not regulated by DNA methylation. Conclusions Our analysis supports the hypothesis that at least for a subset of TF, empirical binding to conserved consensus motifs genome-wide may be controlled by DNA methylation. PMID:20875111

  1. GOmotif: A web server for investigating the biological role of protein sequence motifs

    PubMed Central

    2011-01-01

    Background Many proteins contain conserved sequence patterns (motifs) that contribute to their functionality. The process of experimentally identifying and validating novel protein motifs can be difficult, expensive, and time consuming. A means for helping to identify in advance the possible function of a novel motif is important to test hypotheses concerning the biological relevance of these motifs, thus reducing experimental trial-and-error. Results GOmotif accepts PROSITE and regular expression formatted motifs as input and searches a Gene Ontology annotated protein database using motif search tools. The search returns the set of proteins containing matching motifs and their associated Gene Ontology terms. These results are presented as: 1) a hierarchical, navigable tree separated into the three Gene Ontology biological domains - biological process, cellular component, and molecular function; 2) corresponding pie charts indicating raw and statistically adjusted distributions of the results, and 3) an interactive graphical network view depicting the location of the results in the Gene Ontology. Conclusions GOmotif is a web-based tool designed to assist researchers in investigating the biological role of novel protein motifs. GOmotif can be freely accessed at http://www.gomotif.ca PMID:21943350

  2. Population Genomics and Transcriptional Consequences of Regulatory Motif Variation in Globally Diverse Saccharomyces cerevisiae Strains

    PubMed Central

    Connelly, Caitlin F.; Skelly, Daniel A.; Dunham, Maitreya J.; Akey, Joshua M.

    2013-01-01

    Noncoding genetic variation is known to significantly influence gene expression levels in a growing number of specific cases; however, the patterns of genome-wide noncoding variation present within populations, the evolutionary forces acting on noncoding variants, and the relative effects of regulatory polymorphisms on transcript abundance are not well characterized. Here, we address these questions by analyzing patterns of regulatory variation in motifs for 177 DNA binding proteins in 37 strains of Saccharomyces cerevisiae. Between S. cerevisiae strains, we found considerable polymorphism in regulatory motifs across strains (mean π = 0.005) as well as diversity in regulatory motifs (mean 0.91 motifs differences per regulatory region). Population genetics analyses reveal that motifs are under purifying selection, and there is considerable heterogeneity in the magnitude of selection across different motifs. Finally, we obtained RNA-Seq data in 22 strains and identified 49 polymorphic DNA sequence motifs in 30 distinct genes that are significantly associated with transcriptional differences between strains. In 22 of these genes, there was a single polymorphic motif associated with expression in the upstream region. Our results provide comprehensive insights into the evolutionary trajectory of regulatory variation in yeast and the characteristics of a compendium of regulatory alleles. PMID:23619145

  3. Stabilization of i-motif structures by 2′-β-fluorination of DNA

    PubMed Central

    Assi, Hala Abou; Harkness, Robert W.; Martin-Pintado, Nerea; Wilds, Christopher J.; Campos-Olivas, Ramón; Mittermaier, Anthony K.; González, Carlos; Damha, Masad J.

    2016-01-01

    i-Motifs are four-stranded DNA structures consisting of two parallel DNA duplexes held together by hemi-protonated and intercalated cytosine base pairs (C:CH+). They have attracted considerable research interest for their potential role in gene regulation and their use as pH responsive switches and building blocks in macromolecular assemblies. At neutral and basic pH values, the cytosine bases deprotonate and the structure unfolds into single strands. To avoid this limitation and expand the range of environmental conditions supporting i-motif folding, we replaced the sugar in DNA by 2-deoxy-2-fluoroarabinose. We demonstrate that such a modification significantly stabilizes i-motif formation over a wide pH range, including pH 7. Nuclear magnetic resonance experiments reveal that 2-deoxy-2-fluoroarabinose adopts a C2′-endo conformation, instead of the C3′-endo conformation usually found in unmodified i-motifs. Nevertheless, this substitution does not alter the overall i-motif structure. This conformational change, together with the changes in charge distribution in the sugar caused by the electronegative fluorine atoms, leads to a number of favorable sequential and inter-strand electrostatic interactions. The availability of folded i-motifs at neutral pH will aid investigations into the biological function of i-motifs in vitro, and will expand i-motif applications in nanotechnology. PMID:27166371

  4. The EDLL motif: a potent plant transcriptional activation domain from AP2/ERF transcription factors.

    PubMed

    Tiwari, Shiv B; Belachew, Alemu; Ma, Siu Fong; Young, Melinda; Ade, Jules; Shen, Yu; Marion, Colleen M; Holtan, Hans E; Bailey, Adina; Stone, Jeffrey K; Edwards, Leslie; Wallace, Andreah D; Canales, Roger D; Adam, Luc; Ratcliffe, Oliver J; Repetti, Peter P

    2012-06-01

    In plants, the ERF/EREBP family of transcriptional regulators plays a key role in adaptation to various biotic and abiotic stresses. These proteins contain a conserved AP2 DNA-binding domain and several uncharacterized motifs. Here, we describe a short motif, termed 'EDLL', that is present in AtERF98/TDR1 and other clade members from the same AP2 sub-family. We show that the EDLL motif, which has a unique arrangement of acidic amino acids and hydrophobic leucines, functions as a strong activation domain. The motif is transferable to other proteins, and is active at both proximal and distal positions of target promoters. As such, the EDLL motif is able to partly overcome the repression conferred by the AtHB2 transcription factor, which contains an ERF-associated amphiphilic repression (EAR) motif. We further examined the activation potential of EDLL by analysis of the regulation of flowering time by NF-Y (nuclear factor Y) proteins. Genetic evidence indicates that NF-Y protein complexes potentiate the action of CONSTANS in regulation of flowering in Arabidopsis; we show that the transcriptional activation function of CONSTANS can be substituted by direct fusion of the EDLL activation motif to NF-YB subunits. The EDLL motif represents a potent plant activation domain that can be used as a tool to confer transcriptional activation potential to heterologous DNA-binding proteins.

  5. A generalized profile syntax for biomolecular sequence motifs and its function in automatic sequence interpretation

    SciTech Connect

    Bucher, P.; Bairoch, A.

    1994-12-31

    A general syntax for expressing bimolecular sequence motifs is described, which will be used in future releases of the PROSITE data bank and in a similar collection of nucleic acid sequence motifs currently under development. The central part of the syntax is a regular structure which can be viewed as a generalization of the profiles introduced by Gribskov and coworkers. Accessory features implement specific motif search strategies and provide information helpful for the interpretation of predicted matches. Two contrasting examples, representing E. coli promoters and SH3 domains respectively, are shown to demonstrate the versatility of the syntax, and its compatibility with diverse motif search methods. It is argued, that a comprehensive machine-readable motif collection based on the new syntax, in conjunction with a standard search program, can serve as a general-purpose sequence interpretation and function prediction tool.

  6. Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences

    PubMed Central

    Wright, Elisé P.; Day, Henry A.; Ibrahim, Ali M.; Kumar, Jeethendra; Boswell, Leo J. E.; Huguin, Camille; Stevenson, Clare E. M.; Pors, Klaus; Waller, Zoë A. E.

    2016-01-01

    There are hundreds of ligands which can interact with G-quadruplex DNA, yet very few which target i-motif. To appreciate an understanding between the dynamics between these structures and how they can be affected by intervention with small molecule ligands, more i-motif binding compounds are required. Herein we describe how the drug mitoxantrone can bind, induce folding of and stabilise i-motif forming DNA sequences, even at physiological pH. Additionally, mitoxantrone was found to bind i-motif forming sequences preferentially over double helical DNA. We also describe the stabilisation properties of analogues of mitoxantrone. This offers a new family of ligands with potential for use in experiments into the structure and function of i-motif forming DNA sequences. PMID:28004744

  7. The dimerization motif of the glycophorin A transmembrane segment in membranes: importance of glycine residues.

    PubMed

    Brosig, B; Langosch, D

    1998-04-01

    The glycophorin A transmembrane segment homo-dimerizes to a right-handed pair of alpha-helices. Here, we identified the amino acid motif mediating this interaction within a natural membrane environment. Critical residues were grafted onto two different hydrophobic host sequences in a stepwise manner and self-assembly of the hybrid sequences was determined with the ToxR transcription activator system. Our results show that the motif LIxxGxxxGxxxT elicits a level of self-association equivalent to that of the original glycophorin A transmembrane segment. This motif is very similar to the one previously established in detergent solution. Interestingly, the central GxxxG motif by itself already induced strong self-assembly of host sequences and the three-residue spacing between both glycines proved to be optimal for the interaction. The GxxxG element thus appears to be the most crucial part of the interaction motif.

  8. The dimerization motif of the glycophorin A transmembrane segment in membranes: importance of glycine residues.

    PubMed Central

    Brosig, B.; Langosch, D.

    1998-01-01

    The glycophorin A transmembrane segment homo-dimerizes to a right-handed pair of alpha-helices. Here, we identified the amino acid motif mediating this interaction within a natural membrane environment. Critical residues were grafted onto two different hydrophobic host sequences in a stepwise manner and self-assembly of the hybrid sequences was determined with the ToxR transcription activator system. Our results show that the motif LIxxGxxxGxxxT elicits a level of self-association equivalent to that of the original glycophorin A transmembrane segment. This motif is very similar to the one previously established in detergent solution. Interestingly, the central GxxxG motif by itself already induced strong self-assembly of host sequences and the three-residue spacing between both glycines proved to be optimal for the interaction. The GxxxG element thus appears to be the most crucial part of the interaction motif. PMID:9568912

  9. Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences

    NASA Astrophysics Data System (ADS)

    Wright, Elisé P.; Day, Henry A.; Ibrahim, Ali M.; Kumar, Jeethendra; Boswell, Leo J. E.; Huguin, Camille; Stevenson, Clare E. M.; Pors, Klaus; Waller, Zoë A. E.

    2016-12-01

    There are hundreds of ligands which can interact with G-quadruplex DNA, yet very few which target i-motif. To appreciate an understanding between the dynamics between these structures and how they can be affected by intervention with small molecule ligands, more i-motif binding compounds are required. Herein we describe how the drug mitoxantrone can bind, induce folding of and stabilise i-motif forming DNA sequences, even at physiological pH. Additionally, mitoxantrone was found to bind i-motif forming sequences preferentially over double helical DNA. We also describe the stabilisation properties of analogues of mitoxantrone. This offers a new family of ligands with potential for use in experiments into the structure and function of i-motif forming DNA sequences.

  10. Growing scale-free networks with tunable distributions of triad motifs

    NASA Astrophysics Data System (ADS)

    Li, Shuguang; Yuan, Jianping; Shi, Yong; Zagal, Juan Cristóbal

    2015-06-01

    Network motifs are local structural patterns and elementary functional units of complex networks in real world, which can have significant impacts on the global behavior of these systems. Many models are able to reproduce complex networks mimicking a series of global features of real systems, however the local features such as motifs in real networks have not been well represented. We propose a model to grow scale-free networks with tunable motif distributions through a combined operation of preferential attachment and triad motif seeding steps. Numerical experiments show that the constructed networks have adjustable distributions of the local triad motifs, meanwhile preserving the global features of power-law distributions of node degree, short average path lengths of nodes, and highly clustered structures.

  11. Motif-based construction of a functional map for mammalian olfactory receptors.

    PubMed

    Liu, Agatha H; Zhang, Xinmin; Stolovitzky, Gustavo A; Califano, Andrea; Firestein, Stuart J

    2003-05-01

    We applied an automatic and unsupervised system to a nearly complete database of mammalian odor receptor genes. The generated motifs and gene classification were subjected to extensive and systematic downstream analysis to obtain biological insights. Two major results from this analysis were: (1) a map of sequence motifs that may correlate with function and (2) the corresponding receptor classes in which members of each class are likely to share specific functions. We have discovered motifs that have been implicated in structural integrity and posttranslational modification, as well as motifs very likely to be directly involved in ligand binding. We further propose a combinatorial molecular hypothesis, based on unique combinations of the observed motifs, that provides a foundation for understanding the generation of a large number of ligand binding sites.

  12. Combinatorial Information Theoretical Measurement of the Semantic Significance of Semantic Graph Motifs

    SciTech Connect

    Joslyn, Cliff A.; al-Saffar, Sinan; Haglin, David J.; Holder, Larry

    2011-06-14

    Given an arbitrary semantic graph data set, perhaps one lacking in explicit ontological information, we wish to first identify its significant semantic structures, and then measure the extent of their significance. Casting a semantic graph dataset as an edge-labeled, directed graph, this task can be built on the ability to mine frequent {\\em labeled} subgraphs in edge-labeled, directed graphs. We begin by considering the fundamentals of the enumerative combinatorics of subgraph motif structures in edge-labeled directed graphs. We identify its frequent labeled, directed subgraph motif patterns, and measure the significance of the resulting motifs by the information gain relative to the expected value of the motif based on the empirical frequency distribution of the link types which compose them, assuming indpendence. We illustrate the method on a small test graph, and discuss results obtained for small linear motifs (link type bigrams and trigrams) in a larger graph structure.

  13. Identification of a novel mono-leucine basolateral sorting motif within the cytoplasmic domain of amphiregulin

    PubMed Central

    Gephart, Jonathan D.; Singh, Bhuminder; Higginbotham, James N.; Franklin, Jeffrey L.; Gonzalez, Alfonso; Fölsch, Heike; Coffey, Robert J.

    2011-01-01

    Epithelial cells establish apical and basolateral (BL) membranes with distinct protein and lipid compositions. To achieve this spatial asymmetry, the cell utilizes a variety of mechanisms for differential sorting, delivery and retention of cell surface proteins. The EGF receptor (EGFR) and its ligand, amphiregulin (AREG), are transmembrane proteins delivered to the BL membrane in polarized epithelial cells. Herein, we show that the cytoplasmic domain of AREG contains dominant BL sorting information; replacement of the cytoplasmic domain of apically targeted NGFR with the cytoplasmic domain of AREG redirects the chimera to the BL surface. Using sequential truncations and site-directed mutagenesis of the AREG cytoplasmic domain, we identify a novel BL sorting motif consisting of a single leucine C-terminal to an acidic cluster (EEXXXL). In AP-1B-deficient cells, newly synthesized AREG is initially delivered to the BL surface like in AP-1B-expressing cells. However, in these AP-1B-deficient cells, recycling of AREG back to the BL surface is compromised, leading to its appearance at the apical surface. These results show that recycling, but not delivery, of AREG to the BL surface is AP-1B-dependent. PMID:21917092

  14. Bioinformatics study of cancer-related mutations within p53 phosphorylation site motifs.

    PubMed

    Ji, Xiaona; Huang, Qiang; Yu, Long; Nussinov, Ruth; Ma, Buyong

    2014-07-29

    p53 protein has about thirty phosphorylation sites located at the N- and C-termini and in the core domain. The phosphorylation sites are relatively less mutated than other residues in p53. To understand why and how p53 phosphorylation sites are rarely mutated in human cancer, using a bioinformatics approaches, we examined the phosphorylation site and its nearby flanking residues, focusing on the consensus phosphorylation motif pattern, amino-acid correlations within the phosphorylation motifs, the propensity of structural disorder of the phosphorylation motifs, and cancer mutations observed within the phosphorylation motifs. Many p53 phosphorylation sites are targets for several kinases. The phosphorylation sites match 17 consensus sequence motifs out of the 29 classified. In addition to proline, which is common in kinase specificity-determining sites, we found high propensity of acidic residues to be adjacent to phosphorylation sites. Analysis of human cancer mutations in the phosphorylation motifs revealed that motifs with adjacent acidic residues generally have fewer mutations, in contrast to phosphorylation sites near proline residues. p53 phosphorylation motifs are mostly disordered. However, human cancer mutations within phosphorylation motifs tend to decrease the disorder propensity. Our results suggest that combination of acidic residues Asp and Glu with phosphorylation sites provide charge redundancy which may safe guard against loss-of-function mutations, and that the natively disordered nature of p53 phosphorylation motifs may help reduce mutational damage. Our results further suggest that engineering acidic amino acids adjacent to potential phosphorylation sites could be a p53 gene therapy strategy.

  15. An improved poly(A) motifs recognition method based on decision level fusion.

    PubMed

    Zhang, Shanxin; Han, Jiuqiang; Liu, Jun; Zheng, Jiguang; Liu, Ruiling

    2015-02-01

    Polyadenylation is the process of addition of poly(A) tail to mRNA 3' ends. Identification of motifs controlling polyadenylation plays an essential role in improving genome annotation accuracy and better understanding of the mechanisms governing gene regulation. The bioinformatics methods used for poly(A) motifs recognition have demonstrated that information extracted from sequences surrounding the candidate motifs can differentiate true motifs from the false ones greatly. However, these methods depend on either domain features or string kernels. To date, methods combining information from different sources have not been found yet. Here, we proposed an improved poly(A) motifs recognition method by combing different sources based on decision level fusion. First of all, two novel prediction methods was proposed based on support vector machine (SVM): one method is achieved by using the domain-specific features and principle component analysis (PCA) method to eliminate the redundancy (PCA-SVM); the other method is based on Oligo string kernel (Oligo-SVM). Then we proposed a novel machine-learning method for poly(A) motif prediction by marrying four poly(A) motifs recognition methods, including two state-of-the-art methods (Random Forest (RF) and HMM-SVM), and two novel proposed methods (PCA-SVM and Oligo-SVM). A decision level information fusion method was employed to combine the decision values of different classifiers by applying the DS evidence theory. We evaluated our method on a comprehensive poly(A) dataset that consists of 14,740 samples on 12 variants of poly(A) motifs and 2750 samples containing none of these motifs. Our method has achieved accuracy up to 86.13%. Compared with the four classifiers, our evidence theory based method reduces the average error rate by about 30%, 27%, 26% and 16%, respectively. The experimental results suggest that the proposed method is more effective for poly(A) motif recognition.

  16. Copper-binding tripeptide motif increases potency of the antimicrobial peptide Anoplin via Reactive Oxygen Species generation.

    PubMed

    Libardo, M Daben J; Nagella, Sai; Lugo, Andrea; Pierce, Scott; Angeles-Boza, Alfredo M

    2015-01-02

    Antimicrobial peptides (AMPs) are broad spectrum antimicrobial agents that act through diverse mechanisms, this characteristic makes them suitable starting points for development of novel classes of antibiotics. We have previously reported the increase in activity of AMPs upon addition of the Amino Terminal Copper and Nickel (ATCUN) Binding Unit. Herein we synthesized the membrane active peptide, Anoplin and two ATCUN-Anoplin derivatives and show that the increase in activity is indeed due to the ROS formation by the Cu(II)-ATCUN complex. We found that the ATCUN-Anoplin peptides were up to four times more potent compared to Anoplin alone against standard test bacteria. We studied membrane disruption, and cellular localization and found that addition of the ATCUN motif did not lead to a difference in these properties. When helical content was calculated, we observed that ATCUN-Anoplin had a lower helical composition. We found that ATCUN-Anoplin are able to oxidatively damage lipids in the bacterial membrane and that their activity trails the rate at which ROS is formed by the Cu(II)-ATCUN complexes alone. This study shows that addition of a metal binding tripeptide motif is a simple strategy to increase potency of AMPs by conferring a secondary action.

  17. Isolation, cloning and characterisation of motifs containing (GA/TC)n repeats isolated from vetch, Vicia bithynica.

    PubMed

    Sakowicz, Tomasz; Bowater, Richard; Parniewski, Paweł

    2004-01-01

    Microsatellites are widely distributed in plant genomes and comprise unstable regions that undergo mutational changes at rates much greater than that observed for non-repetitive sequences. They demonstrate intrinsic genetic instability, manifested as frequent length changes due to insertions or deletions of repeat units. Detailed analysis of 1600 clones containing genomic sequences of Vicia bithynica revealed the presence of microsatellite repeats in its genome. Based on the screening of a partial DNA library of plasmids, 13 clones harbouring (GA/TC)n tracts of various lengths of repeated motif were identified for further analysis of their internal sequence organization. Sequence analyses revealed the precise length, number of repeats, interruptions within tracts, as well as sequence composition flanking the repeat motifs. Representative plasmids containing different lengths of (GA/TC)n embedded in their original flanking sequence were used to investigate the genetic stability of the repeats. In the study presented herein, we employed a well characterised and tractable bacterial genetic system. Recultivations of Escherichia coli harbouring plasmids containing (GA/TC)n inserts demonstrated that the genetic instability of (GA/TC)n microsatellites depends highly on their length (number of repeats). These observations are in agreement with similar studies performed on repetitive sequences from humans and other organisms.

  18. One motif to bind them: A small-XXX-small motif affects transmembrane domain 1 oligomerization, function, localization, and cross-talk between two yeast GPCRs.

    PubMed

    Lock, Antonia; Forfar, Rachel; Weston, Cathryn; Bowsher, Leo; Upton, Graham J G; Reynolds, Christopher A; Ladds, Graham; Dixon, Ann M

    2014-12-01

    G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors in mammals and facilitate a range of physiological responses triggered by a variety of ligands. GPCRs were thought to function as monomers, however it is now accepted that GPCR homo- and hetero-oligomers also exist and influence receptor properties. The Schizosaccharomyces pombe GPCR Mam2 is a pheromone-sensing receptor involved in mating and has previously been shown to form oligomers in vivo. The first transmembrane domain (TMD) of Mam2 contains a small-XXX-small motif, overrepresented in membrane proteins and well-known for promoting helix-helix interactions. An ortholog of Mam2 in Saccharomyces cerevisiae, Ste2, contains an analogous small-XXX-small motif which has been shown to contribute to receptor homo-oligomerization, localization and function. Here we have used experimental and computational techniques to characterize the role of the small-XXX-small motif in function and assembly of Mam2 for the first time. We find that disruption of the motif via mutagenesis leads to reduction of Mam2 TMD1 homo-oligomerization and pheromone-responsive cellular signaling of the full-length protein. It also impairs correct targeting to the plasma membrane. Mutation of the analogous motif in Ste2 yielded similar results, suggesting a conserved mechanism for assembly. Using co-expression of the two fungal receptors in conjunction with computational models, we demonstrate a functional change in G protein specificity and propose that this is brought about through hetero-dimeric interactions of Mam2 with Ste2 via the complementary small-XXX-small motifs. This highlights the potential of these motifs to affect a range of properties that can be investigated in other GPCRs.

  19. Identification of single C motif-1/lymphotactin receptor XCR1.

    PubMed

    Yoshida, T; Imai, T; Kakizaki, M; Nishimura, M; Takagi, S; Yoshie, O

    1998-06-26

    Single C motif-1 (SCM-1)/lymphotactin is a member of the chemokine superfamily, but retains only the 2nd and 4th of the four cysteine residues conserved in other chemokines. In humans, there are two highly homologous SCM-1 genes encoding SCM-1alpha and SCM-1beta with two amino acid substitutions. To identify a specific receptor for SCM-1 proteins, we produced recombinant SCM-1alpha and SCM-1beta by the baculovirus expression system and tested them on murine L1.2 cells stably expressing eight known chemokine receptors and three orphan receptors. Both proteins specifically induced migration in cells expressing an orphan receptor, GPR5. The migration was chemotactic and suppressed by pertussis toxin, indicating coupling to a Galpha type of G protein. Both proteins also induced intracellular calcium mobilization in GPR5-expressing L1.2 cells with efficient mutual cross desensitization. SCM-1alpha bound specifically to GPR5-expressing L1.2 cells with a Kd of 10 nM. By Northern blot analysis, GPR5 mRNA of about 5 kilobases was detected strongly in placenta and weakly in spleen and thymus among various human tissues. Identification of a specific receptor for SCM-1 would facilitate our investigation on its biological function. Following the set rule for the chemokine receptor nomenclature, we propose to designate GPR5 as XCR1 from XC chemokine receptor-1.

  20. Ab initio coordination chemistry for nickel chelation motifs.

    PubMed

    Sudan, R Jesu Jaya; Kumari, J Lesitha Jeeva; Sudandiradoss, C

    2015-01-01

    Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies.

  1. Peptide motif analysis predicts alphaviruses as triggers for rheumatoid arthritis.

    PubMed

    Hogeboom, Charissa

    2015-12-01

    Rheumatoid arthritis (RA) develops in response to both genetic and environmental factors. The strongest genetic determinant is HLA-DR, where polymorphisms within the P4 and P6 binding pockets confer elevated risk. However, low disease concordance across monozygotic twin pairs underscores the importance of an environmental factor, probably infectious. The goal of this investigation was to predict the microorganism most likely to interact with HLA-DR to trigger RA under the molecular mimicry hypothesis. A set of 185 structural proteins from viruses or intracellular bacteria was scanned for regions of sequence homology with a collagen peptide that binds preferentially to DR4; candidates were then evaluated against a motif required for T cell cross-reactivity. The plausibility of the predicted agent was evaluated by comparison of microbial prevalence patterns to epidemiological characteristics of RA. Peptides from alphavirus capsid proteins provided the closest fit. Variations in the P6 position suggest that the HLA binding preference may vary by species, with Ross River virus, Chikungunya virus, and Mayaro virus peptides binding preferentially to DR4, and peptides from Sindbis/Ockelbo virus showing stronger affinity to DR1. The predicted HLA preference is supported by epidemiological studies of post-infection chronic arthralgia. Parallels between the cytokine profiles of RA and chronic alphavirus infection are discussed.

  2. Network motifs that stabilize the hybrid epithelial/mesenchymal phenotype

    NASA Astrophysics Data System (ADS)

    Jolly, Mohit Kumar; Jia, Dongya; Tripathi, Satyendra; Hanash, Samir; Mani, Sendurai; Ben-Jacob, Eshel; Levine, Herbert

    Epithelial to Mesenchymal Transition (EMT) and its reverse - MET - are hallmarks of cancer metastasis. While transitioning between E and M phenotypes, cells can also attain a hybrid epithelial/mesenchymal (E/M) phenotype that enables collective cell migration as a cluster of Circulating Tumor Cells (CTCs). These clusters can form 50-times more tumors than individually migrating CTCs, underlining their importance in metastasis. However, this hybrid E/M phenotype has been hypothesized to be only a transient one that is attained en route EMT. Here, via mathematically modeling, we identify certain `phenotypic stability factors' that couple with the core three-way decision-making circuit (miR-200/ZEB) and can maintain or stabilize the hybrid E/M phenotype. Further, we show experimentally that this phenotype can be maintained stably at a single-cell level, and knockdown of these factors impairs collective cell migration. We also show that these factors enable the association of hybrid E/M with high stemness or tumor-initiating potential. Finally, based on these factors, we deduce specific network motifs that can maintain the E/M phenotype. Our framework can be used to elucidate the effect of other players in regulating cellular plasticity during metastasis. This work was supported by NSF PHY-1427654 (Center for Theoretical Biological Physics) and the CPRIT Scholar in Cancer Research of the State of Texas at Rice University.

  3. Evidence for a gamma-turn motif in antifreeze glycopeptides.

    PubMed Central

    Drewes, J A; Rowlen, K L

    1993-01-01

    Knowledge of the secondary structure of antifreeze peptides (AFPs) and glycopeptides (AFGPs) is crucial to understanding the mechanism by which these molecules inhibit ice crystal growth. A polyproline type II helix is perhaps the most widely accepted conformation for active AFGPs; however, random coil and alpha-helix conformations have also been proposed. In this report we present vibrational spectroscopic evidence that the conformation of AFGPs in solution is not random, not alpha-helical, and not polyproline type II. Comparison of AFGP amide vibrational frequencies with those observed and calculated for beta and gamma-turns in other peptides strongly suggests that AFGPs contain substantial turn structure. Computer-generated molecular models were utilized to compare gamma-turn, beta-turn, and polyproline II structures. The gamma-turn motif is consistent with observed amide frequencies and results in a molecule with planar symmetry with respect to the disaccharides. This intriguing conformation may provide new insight into the unusual properties of AFGPs. Images FIGURE 6 PMID:8241413

  4. Eukaryotic Penelope-Like Retroelements Encode Hammerhead Ribozyme Motifs

    PubMed Central

    Cervera, Amelia; De la Peña, Marcos

    2014-01-01

    Small self-cleaving RNAs, such as the paradigmatic Hammerhead ribozyme (HHR), have been recently found widespread in DNA genomes across all kingdoms of life. In this work, we found that new HHR variants are preserved in the ancient family of Penelope-like elements (PLEs), a group of eukaryotic retrotransposons regarded as exceptional for encoding telomerase-like retrotranscriptases and spliceosomal introns. Our bioinformatic analysis revealed not only the presence of minimalist HHRs in the two flanking repeats of PLEs but also their massive and widespread occurrence in metazoan genomes. The architecture of these ribozymes indicates that they may work as dimers, although their low self-cleavage activity in vitro suggests the requirement of other factors in vivo. In plants, however, PLEs show canonical HHRs, whereas fungi and protist PLEs encode ribozyme variants with a stable active conformation as monomers. Overall, our data confirm the connection of self-cleaving RNAs with eukaryotic retroelements and unveil these motifs as a significant fraction of the encoded information in eukaryotic genomes. PMID:25135949

  5. Motif mimetic of epsin perturbs tumor growth and metastasis

    PubMed Central

    Dong, Yunzhou; Wu, Hao; Rahman, H.N. Ashiqur; Liu, Yanjun; Pasula, Satish; Tessneer, Kandice L.; Cai, Xiaofeng; Liu, Xiaolei; Chang, Baojun; McManus, John; Hahn, Scott; Dong, Jiali; Brophy, Megan L.; Yu, Lili; Song, Kai; Silasi-Mansat, Robert; Saunders, Debra; Njoku, Charity; Song, Hoogeun; Mehta-D’Souza, Padmaja; Towner, Rheal; Lupu, Florea; McEver, Rodger P.; Xia, Lijun; Boerboom, Derek; Srinivasan, R. Sathish; Chen, Hong

    2015-01-01

    Tumor angiogenesis is critical for cancer progression. In multiple murine models, endothelium-specific epsin deficiency abrogates tumor progression by shifting the balance of VEGFR2 signaling toward uncontrolled tumor angiogenesis, resulting in dysfunctional tumor vasculature. Here, we designed a tumor endothelium–targeting chimeric peptide (UPI) for the purpose of inhibiting endogenous tumor endothelial epsins by competitively binding activated VEGFR2. We determined that the UPI peptide specifically targets tumor endothelial VEGFR2 through an unconventional binding mechanism that is driven by unique residues present only in the epsin ubiquitin–interacting motif (UIM) and the VEGFR2 kinase domain. In murine models of neoangiogenesis, UPI peptide increased VEGF-driven angiogenesis and neovascularization but spared quiescent vascular beds. Further, in tumor-bearing mice, UPI peptide markedly impaired functional tumor angiogenesis, tumor growth, and metastasis, resulting in a notable increase in survival. Coadministration of UPI peptide with cytotoxic chemotherapeutics further sustained tumor inhibition. Equipped with localized tumor endothelium–specific targeting, our UPI peptide provides potential for an effective and alternative cancer therapy. PMID:26571402

  6. Crammed signaling motifs in the T-cell receptor.

    PubMed

    Borroto, Aldo; Abia, David; Alarcón, Balbino

    2014-09-01

    Although the T cell antigen receptor (TCR) is long known to contain multiple signaling subunits (CD3γ, CD3δ, CD3ɛ and CD3ζ), their role in signal transduction is still not well understood. The presence of at least one immunoreceptor tyrosine-based activation motif (ITAM) in each CD3 subunit has led to the idea that the multiplication of such elements essentially serves to amplify signals. However, the evolutionary conservation of non-ITAM sequences suggests that each CD3 subunit is likely to have specific non-redundant roles at some stage of development or in mature T cell function. The CD3ɛ subunit is paradigmatic because in a relatively short cytoplasmic sequence (∼55 amino acids) it contains several docking sites for proteins involved in intracellular trafficking and signaling, proteins whose relevance in T cell activation is slowly starting to be revealed. In this review we will summarize our current knowledge on the signaling effectors that bind directly to the TCR and we will propose a hierarchy in their response to TCR triggering.

  7. Organizational motifs for ground squirrel cone bipolar cells.

    PubMed

    Light, Adam C; Zhu, Yongling; Shi, Jun; Saszik, Shannon; Lindstrom, Sarah; Davidson, Laura; Li, Xiaoyu; Chiodo, Vince A; Hauswirth, William W; Li, Wei; DeVries, Steven H

    2012-09-01

    In daylight vision, parallel processing starts at the cone synapse. Cone signals flow to On and Off bipolar cells, which are further divided into types according to morphology, immunocytochemistry, and function. The axons of the bipolar cell types stratify at different levels in the inner plexiform layer (IPL) and can interact with costratifying amacrine and ganglion cells. These interactions endow the ganglion cell types with unique functional properties. The wiring that underlies the interactions among bipolar, amacrine, and ganglion cells is poorly understood. It may be easier to elucidate this wiring if organizational rules can be established. We identify 13 types of cone bipolar cells in the ground squirrel, 11 of which contact contiguous cones, with the possible exception of short-wavelength-sensitive cones. Cells were identified by antibody labeling, tracer filling, and Golgi-like filling following transduction with an adeno-associated virus encoding for green fluorescent protein. The 11 bipolar cell types displayed two organizational patterns. In the first pattern, eight to 10 of the 11 types came in pairs with partially overlapping axonal stratification. Pairs shared morphological, immunocytochemical, and functional properties. The existence of similar pairs is a new motif that might have implications for how signals first diverge from a cone to bipolar cells and then reconverge onto a costratifying ganglion cell. The second pattern is a mirror symmetric organization about the middle of the IPL involving at least seven bipolar cell types. This anatomical symmetry may be associated with a functional symmetry in On and Off ganglion cell responses.

  8. Information processing by simple molecular motifs and susceptibility to noise.

    PubMed

    Mc Mahon, Siobhan S; Lenive, Oleg; Filippi, Sarah; Stumpf, Michael P H

    2015-09-06

    Biological organisms rely on their ability to sense and respond appropriately to their environment. The molecular mechanisms that facilitate these essential processes are however subject to a range of random effects and stochastic processes, which jointly affect the reliability of information transmission between receptors and, for example, the physiological downstream response. Information is mathematically defined in terms of the entropy; and the extent of information flowing across an information channel or signalling system is typically measured by the 'mutual information', or the reduction in the uncertainty about the output once the input signal is known. Here, we quantify how extrinsic and intrinsic noise affects the transmission of simple signals along simple motifs of molecular interaction networks. Even for very simple systems, the effects of the different sources of variability alone and in combination can give rise to bewildering complexity. In particular, extrinsic variability is apt to generate 'apparent' information that can, in extreme cases, mask the actual information that for a single system would flow between the different molecular components making up cellular signalling pathways. We show how this artificial inflation in apparent information arises and how the effects of different types of noise alone and in combination can be understood.

  9. Plasticity of the RNA Kink Turn Structural Motif

    SciTech Connect

    Antonioli, A.; Cochrane, J; Lipchock, S; Strobel, S

    2010-01-01

    The kink turn (K-turn) is an RNA structural motif found in many biologically significant RNAs. While most examples of the K-turn have a similar fold, the crystal structure of the Azoarcus group I intron revealed a novel RNA conformation, a reverse kink turn bent in the direction opposite that of a consensus K-turn. The reverse K-turn is bent toward the major grooves rather than the minor grooves of the flanking helices, yet the sequence differs from the K-turn consensus by only a single nucleotide. Here we demonstrate that the reverse bend direction is not solely defined by internal sequence elements, but is instead affected by structural elements external to the K-turn. It bends toward the major groove under the direction of a tetraloop-tetraloop receptor. The ability of one sequence to form two distinct structures demonstrates the inherent plasticity of the K-turn sequence. Such plasticity suggests that the K-turn is not a primary element in RNA folding, but instead is shaped by other structural elements within the RNA or ribonucleoprotein assembly.

  10. Materiaux composites supraconducteurs

    NASA Astrophysics Data System (ADS)

    Kerjouan, Philippe; Boterel, Florence; Lostec, Jean; Bertot, Jean-Paul; Haussonne, Jean-Marie

    1991-11-01

    The new superconductor materials with a high critical current own a large importance as well in the electronic components or in the electrotechnical devices fields. The deposit of such materials with the thick films technology is to be more and more developped in the years to come. Therefore, we tried to realize such thick films screen printed on alumina, and composed mainly of the YBa2CU3O{7-δ} material. We first realized a composite material glass/YBa2CU3O{7-δ}, by analogy with the classical screen-printed inks where the glass ensures the bonding with the substrate. We thus realized different materials by using some different classes of glass. These materials owned a superconducting transition close to the one of the pure YBa2CU3O{7-δ} material. We made a slurry with the most significant composite materials and binders, and screen-printed them on an alumina substrate preliminary or not coated with a diffusion barrier layer. After firing, we studied the thick films adhesion, the alumina/glass/composite material interfaces, and their superconducting properties. Les nouveaux matériaux supraconducteurs à haute température critique ont potentiellement un rôle important à jouer dans le domaine de l'électronique et de l'électrotechnique. En particulier, le dépôt d'oxydes supraconducteurs sur divers types de substrats est une technologie amenée à se développer. Nous avons donc entrepris une étude dont l'objet est la réalisation de conducteurs sérigraphiés sur alumine et composés essentiellement du matériau YBa2CU3O{7-δ}. Nous avons tout d'abord cherché à réaliser un composite verre/YBa2CU3O{7-δ}, par analogie au principe de réalisation de couches conductrices sérigraphiées, le verre permettant d'obtenir une liaison physico-chimique avec le substrat. Une étude préliminaire a permis de réaliser divers matériaux composites massifs, utilisant différentes familles de verres. Ces matériaux massifs, se présentant sous la forme de barreaux de

  11. LibME-automatic extraction of 3D ligand-binding motifs for mechanistic analysis of protein-ligand recognition.

    PubMed

    He, Wei; Liang, Zhi; Teng, MaiKun; Niu, LiWen

    2016-12-01

    Identifying conserved binding motifs is an efficient way to study protein-ligand recognition. Most 3D binding motifs only contain information from the protein side, and so motifs that combine information from both protein and ligand sides are desired. Here, we propose an algorithm called LibME (Ligand-binding Motif Extractor), which automatically extracts 3D binding motifs composed of the target ligand and surrounding conserved residues. We show that the motifs extracted by LibME for ATP and its analogs are highly similar to well-known motifs reported by previous studies. The superiority of our method to handle flexible ligands was also demonstrated using isocitric acid as an example. Finally, we show that these motifs, together with their visual exhibition, permit better investigating and understanding of protein-ligand recognition process.

  12. Mental imagery boosts music compositional creativity

    PubMed Central

    Lim, Stephen Wee Hun

    2017-01-01

    We empirically investigated the effect of mental imagery on young children’s music compositional creativity. Children aged 5 to 8 years participated in two music composition sessions. In the control session, participants based their composition on a motif that they had created using a sequence of letter names. In the mental imagery session, participants were given a picture of an animal and instructed to imagine the animal’s sounds and movements, before incorporating what they had imagined into their composition. Six expert judges independently rated all music compositions on creativity based on subjective criteria (consensual assessment). Reliability analyses indicated that the expert judges demonstrated a high level of agreement in their ratings. The mental imagery compositions received significantly higher creativity ratings by the expert judges than did the control compositions. These results provide evidence for the effectiveness of mental imagery in enhancing young children’s music compositional creativity. PMID:28296965

  13. Mental imagery boosts music compositional creativity.

    PubMed

    Wong, Sarah Shi Hui; Lim, Stephen Wee Hun

    2017-01-01

    We empirically investigated the effect of mental imagery on young children's music compositional creativity. Children aged 5 to 8 years participated in two music composition sessions. In the control session, participants based their composition on a motif that they had created using a sequence of letter names. In the mental imagery session, participants were given a picture of an animal and instructed to imagine the animal's sounds and movements, before incorporating what they had imagined into their composition. Six expert judges independently rated all music compositions on creativity based on subjective criteria (consensual assessment). Reliability analyses indicated that the expert judges demonstrated a high level of agreement in their ratings. The mental imagery compositions received significantly higher creativity ratings by the expert judges than did the control compositions. These results provide evidence for the effectiveness of mental imagery in enhancing young children's music compositional creativity.

  14. Peptide-based identification of functional motifs and their binding partners.

    PubMed

    Shelton, Martin N; Huang, Ming Bo; Ali, Syed; Johnson, Kateena; Roth, William; Powell, Michael; Bond, Vincent

    2013-06-30

    Specific short peptides derived from motifs found in full-length proteins, in our case HIV-1 Nef, not only retain their biological function, but can also competitively inhibit the function of the full-length protein. A set of 20 Nef scanning peptides, 20 amino acids in length with each overlapping 10 amino acids of its neighbor, were used to identify motifs in Nef responsible for its induction of apoptosis. Peptides containing these apoptotic motifs induced apoptosis at levels comparable to the full-length Nef protein. A second peptide, derived from the Secretion Modification Region (SMR) of Nef, retained the ability to interact with cellular proteins involved in Nef's secretion in exosomes (exNef). This SMRwt peptide was used as the "bait" protein in co-immunoprecipitation experiments to isolate cellular proteins that bind specifically to Nef's SMR motif. Protein transfection and antibody inhibition was used to physically disrupt the interaction between Nef and mortalin, one of the isolated SMR-binding proteins, and the effect was measured with a fluorescent-based exNef secretion assay. The SMRwt peptide's ability to outcompete full-length Nef for cellular proteins that bind the SMR motif, make it the first inhibitor of exNef secretion. Thus, by employing the techniques described here, which utilize the unique properties of specific short peptides derived from motifs found in full-length proteins, one may accelerate the identification of functional motifs in proteins and the development of peptide-based inhibitors of pathogenic functions.

  15. A novel motif in telomerase reverse transcriptase regulates telomere repeat addition rate and processivity

    PubMed Central

    Xie, Mingyi; Podlevsky, Joshua D.; Qi, Xiaodong; Bley, Christopher J.; Chen, Julian J.-L.

    2010-01-01

    Telomerase is a specialized reverse transcriptase that adds telomeric DNA repeats onto chromosome termini. Here, we characterize a new telomerase-specific motif, called motif 3, in the catalytic domain of telomerase reverse transcriptase, that is crucial for telomerase function and evolutionally conserved between vertebrates and ciliates. Comprehensive mutagenesis of motif 3 identified mutations that remarkably increase the rate or alter the processivity of telomere repeat addition. Notably, the rate and processivity of repeat addition are affected independently by separate motif 3 mutations. The processive telomerase action relies upon a template translocation mechanism whereby the RNA template and the telomeric DNA strand separate and realign between each repeat synthesis. By analyzing the mutant telomerases reconstituted in vitro and in cells, we show that the hyperactive mutants exhibit higher repeat addition rates and faster enzyme turnovers, suggesting higher rates of strand-separation during template translocation. In addition, the strong correlation between the processivity of the motif 3 mutants and their ability to use an 8 nt DNA primer, suggests that motif 3 facilitates realignment between the telomeric DNA and the template RNA following strand-separation. These findings support motif 3 as a key determinant for telomerase activity and processivity. PMID:20044353

  16. Trend Motif: A Graph Mining Approach for Analysis of Dynamic Complex Networks

    SciTech Connect

    Jin, R; McCallen, S; Almaas, E

    2007-05-28

    Complex networks have been used successfully in scientific disciplines ranging from sociology to microbiology to describe systems of interacting units. Until recently, studies of complex networks have mainly focused on their network topology. However, in many real world applications, the edges and vertices have associated attributes that are frequently represented as vertex or edge weights. Furthermore, these weights are often not static, instead changing with time and forming a time series. Hence, to fully understand the dynamics of the complex network, we have to consider both network topology and related time series data. In this work, we propose a motif mining approach to identify trend motifs for such purposes. Simply stated, a trend motif describes a recurring subgraph where each of its vertices or edges displays similar dynamics over a userdefined period. Given this, each trend motif occurrence can help reveal significant events in a complex system; frequent trend motifs may aid in uncovering dynamic rules of change for the system, and the distribution of trend motifs may characterize the global dynamics of the system. Here, we have developed efficient mining algorithms to extract trend motifs. Our experimental validation using three disparate empirical datasets, ranging from the stock market, world trade, to a protein interaction network, has demonstrated the efficiency and effectiveness of our approach.

  17. Recurrent motifs as resonant attractor states in the narrative field: a testable model of archetype.

    PubMed

    Goodwyn, Erik

    2013-06-01

    At the most basic level, archetypes represented Jung's attempt to explain the phenomenon of recurrent myths and folktale motifs (Jung 1956, 1959, para. 99). But the archetype remains controversial as an explanation of recurrent motifs, as the existence of recurrent motifs does not prove that archetypes exist. Thus, the challenge for contemporary archetype theory is not merely to demonstrate that recurrent motifs exist, since that is not disputed, but to demonstrate that archetypes exist and cause recurrent motifs. The present paper proposes a new model which is unlike others in that it postulates how the archetype creates resonant motifs. This model necessarily clarifies and adapts some of Jung's seminal ideas on archetype in order to provide a working framework grounded in contemporary practice and methodologies. For the first time, a model of archetype is proposed that can be validated on empirical, rather than theoretical grounds. This is achieved by linking the archetype to the hard data of recurrent motifs rather than academic trends in other fields.

  18. SVM2Motif—Reconstructing Overlapping DNA Sequence Motifs by Mimicking an SVM Predictor

    PubMed Central

    Vidovic, Marina M. -C.; Görnitz, Nico; Müller, Klaus-Robert; Rätsch, Gunnar; Kloft, Marius

    2015-01-01

    Identifying discriminative motifs underlying the functionality and evolution of organisms is a major challenge in computational biology. Machine learning approaches such as support vector machines (SVMs) achieve state-of-the-art performances in genomic discrimination tasks, but—due to its black-box character—motifs underlying its decision function are largely unknown. As a remedy, positional oligomer importance matrices (POIMs) allow us to visualize the significance of position-specific subsequences. Although being a major step towards the explanation of trained SVM models, they suffer from the fact that their size grows exponentially in the length of the motif, which renders their manual inspection feasible only for comparably small motif sizes, typically k ≤ 5. In this work, we extend the work on positional oligomer importance matrices, by presenting a new machine-learning methodology, entitled motifPOIM, to extract the truly relevant motifs—regardless of their length and complexity—underlying the predictions of a trained SVM model. Our framework thereby considers the motifs as free parameters in a probabilistic model, a task which can be phrased as a non-convex optimization problem. The exponential dependence of the POIM size on the oligomer length poses a major numerical challenge, which we address by an efficient optimization framework that allows us to find possibly overlapping motifs consisting of up to hundreds of nucleotides. We demonstrate the efficacy of our approach on a synthetic data set as well as a real-world human splice site data set. PMID:26690911

  19. MODA: an efficient algorithm for network motif discovery in biological networks.

    PubMed

    Omidi, Saeed; Schreiber, Falk; Masoudi-Nejad, Ali

    2009-10-01

    In recent years, interest has been growing in the study of complex networks. Since Erdös and Rényi (1960) proposed their random graph model about 50 years ago, many researchers have investigated and shaped this field. Many indicators have been proposed to assess the global features of networks. Recently, an active research area has developed in studying local features named motifs as the building blocks of networks. Unfortunately, network motif discovery is a computationally hard problem and finding rather large motifs (larger than 8 nodes) by means of current algorithms is impractical as it demands too much computational effort. In this paper, we present a new algorithm (MODA) that incorporates techniques such as a pattern growth approach for extracting larger motifs efficiently. We have tested our algorithm and found it able to identify larger motifs with more than 8 nodes more efficiently than most of the current state-of-the-art motif discovery algorithms. While most of the algorithms rely on induced subgraphs as motifs of the networks, MODA is able to extract both induced and non-induced subgraphs simultaneously. The MODA source code is freely available at: http://LBB.ut.ac.ir/Download/LBBsoft/MODA/

  20. Repression domains of class II ERF transcriptional repressors share an essential motif for active repression.

    PubMed

    Ohta, M; Matsui, K; Hiratsu, K; Shinshi, H; Ohme-Takagi, M

    2001-08-01

    We reported previously that three ERF transcription factors, tobacco ERF3 (NtERF3) and Arabidopsis AtERF3 and AtERF4, which are categorized as class II ERFs, are active repressors of transcription. To clarify the roles of these repressors in transcriptional regulation in plants, we attempted to identify the functional domains of the ERF repressor that mediates the repression of transcription. Analysis of the results of a series of deletions revealed that the C-terminal 35 amino acids of NtERF3 are sufficient to confer the capacity for repression of transcription on a heterologous DNA binding domain. This repression domain suppressed the intermolecular activities of other transcriptional activators. In addition, fusion of this repression domain to the VP16 activation domain completely inhibited the transactivation function of VP16. Comparison of amino acid sequences of class II ERF repressors revealed the conservation of the sequence motif (L)/(F)DLN(L)/(F)(x)P. This motif was essential for repression because mutations within the motif eliminated the capacity for repression. We designated this motif the ERF-associated amphiphilic repression (EAR) motif, and we identified this motif in a number of zinc-finger proteins from wheat, Arabidopsis, and petunia plants. These zinc finger proteins functioned as repressors, and their repression domains were identified as regions that contained an EAR motif.

  1. Minimal motif peptide structure of metzincin clan zinc peptidases in micelles.

    PubMed

    Onoda, Akira; Suzuki, Takako; Ishizuka, Hiroaki; Sugiyama, Rumiko; Ariyasu, Shinya; Yamamura, Takeshi

    2009-12-01

    It is well known that the functions of metalloproteins generally originate from their metal-binding motifs. However, the intrinsic nature of individual motifs remains unknown, particularly the details about metal-binding effects on the folding of motifs; the converse is also unknown, although there is no doubt that the motif is the core of the reactivity for each metalloprotein. In this study, we focused our attention on the zinc-binding motif of the metzincin clan family, HEXXHXXGXXH; this family contains the general zinc-binding sequence His-Glu-Xaa-Xaa-His (HEXXH) and the extended GXXH region. We adopted the motif sequence of stromelysin-1 and investigated the folding properties of the Trp-labeled peptides WAHEIAHSLGLFHA (STR-W1), AWHEIAHSLGLFHA (STR-W2), AHEIAHSLGWFHA (STR-W11), and AHEIAHSLGLFHWA (STR-W14) in the presence and absence of zinc ions in hydrophobic micellar environments by circular dichroism (CD) measurements. We accessed successful incorporation of these zinc peptides into micelles using quenching of Trp fluorescence. Results of CD studies indicated that two of the Trp-incorporated peptides, STR-W1 and STR-W14, exhibited helical folding in the hydrophobic region of cetyltrimethylammonium chloride micelle. The NMR structural analysis of the apo STR-W14 revealed that the conformation in the C-terminus GXXH region significantly differred between the apo state in the micelle and the reported Zn-bound state of stromelysin-1 in crystal structures. The structural analyses of the qualitative Zn-binding properties of this motif peptide provide an interesting Zn-binding mechanism: the minimum consensus motif in the metzincin clan, a basic zinc-binding motif with an extended GXXH region, has the potential to serve as a preorganized Zn binding scaffold in a hydrophobic environment.

  2. Identification of a putative nuclear export signal motif in human NANOG homeobox domain

    SciTech Connect

    Park, Sung-Won; Do, Hyun-Jin; Huh, Sun-Hyung; Sung, Boreum; Uhm, Sang-Jun; Song, Hyuk; Kim, Nam-Hyung; Kim, Jae-Hwan

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer We found the putative nuclear export signal motif within human NANOG homeodomain. Black-Right-Pointing-Pointer Leucine-rich residues are important for human NANOG homeodomain nuclear export. Black-Right-Pointing-Pointer CRM1-specific inhibitor LMB blocked the potent human NANOG NES-mediated nuclear export. -- Abstract: NANOG is a homeobox-containing transcription factor that plays an important role in pluripotent stem cells and tumorigenic cells. To understand how nuclear localization of human NANOG is regulated, the NANOG sequence was examined and a leucine-rich nuclear export signal (NES) motif ({sup 125}MQELSNILNL{sup 134}) was found in the homeodomain (HD). To functionally validate the putative NES motif, deletion and site-directed mutants were fused to an EGFP expression vector and transfected into COS-7 cells, and the localization of the proteins was examined. While hNANOG HD exclusively localized to the nucleus, a mutant with both NLSs deleted and only the putative NES motif contained (hNANOG HD-{Delta}NLSs) was predominantly cytoplasmic, as observed by nucleo/cytoplasmic fractionation and Western blot analysis as well as confocal microscopy. Furthermore, site-directed mutagenesis of the putative NES motif in a partial hNANOG HD only containing either one of the two NLS motifs led to localization in the nucleus, suggesting that the NES motif may play a functional role in nuclear export. Furthermore, CRM1-specific nuclear export inhibitor LMB blocked the hNANOG potent NES-mediated export, suggesting that the leucine-rich motif may function in CRM1-mediated nuclear export of hNANOG. Collectively, a NES motif is present in the hNANOG HD and may be functionally involved in CRM1-mediated nuclear export pathway.

  3. Dispom: a discriminative de-novo motif discovery tool based on the jstacs library.

    PubMed

    Grau, Jan; Keilwagen, Jens; Gohr, André; Paponov, Ivan A; Posch, Stefan; Seifert, Michael; Strickert, Marc; Grosse, Ivo

    2013-02-01

    DNA-binding proteins are a main component of gene regulation as they activate or repress gene expression by binding to specific binding sites in target regions of genomic DNA. However, de-novo discovery of these binding sites in target regions obtained by wet-lab experiments is a challenging problem in computational biology, which has not yet been solved satisfactorily. Here, we present a detailed description and analysis of the de-novo motif discovery tool Dispom, which has been developed for finding binding sites of DNA-binding proteins that are differentially abundant in a set of target regions compared to a set of control regions. Two additional features of Dispom are its capability of modeling positional preferences of binding sites and adjusting the length of the motif in the learning process. Dispom yields an increased prediction accuracy compared to existing tools for de-novo motif discovery, suggesting that the combination of searching for differentially abundant motifs, inferring their positional distributions, and adjusting the motif lengths is beneficial for de-novo motif discovery. When applying Dispom to promoters of auxin-responsive genes and those of ABI3 target genes from Arabidopsis thaliana, we identify relevant binding motifs with pronounced positional distributions. These results suggest that learning motifs, their positional distributions, and their lengths by a discriminative learning principle may aid motif discovery from ChIP-chip and gene expression data. We make Dispom freely available as part of Jstacs, an open-source Java library that is tailored to statistical sequence analysis. To facilitate extensions of Dispom, we describe its implementation using Jstacs in this manuscript. In addition, we provide a stand-alone application of Dispom at http://www.jstacs.de/index.php/Dispom for instant use.

  4. Regulatory motifs are present in the ITS1 of some flatworm species.

    PubMed

    Van Herwerden, Lynne; Caley, M Julian; Blair, David

    2003-04-15

    Particular sequence motifs can act as transcription regulators. Because the total regulatory effects of such motifs can be related to their abundance, their presence might be expected at locations within the genome where sequences are repeated. Multiple repeats that vary in number among individuals occur within the ribosomal first internal transcribed spacer (ITS1) in some species in three trematode genera: Paragonimus, Schistosoma and Dolichosaccus. In all of these genera we found in ITS1, sequences identical to known enhancer motifs. We also searched for, and identified, known regulatory motifs in published ITS1 sequences of other parasitic flatworms including Echinostoma spp. (Trematoda) and Echinococcus spp. (Cestoda) which lack multiple repeats in ITS1. We present three lines of evidence that this widespread occurrence of such motifs within the ITS1 of parasitic flatworms may indicate a functional role in regulating tissue- or stage-specific transcription of ribosomal genes. First, these motifs are identical to ones whose functional roles have been established using in vitro assays of transcriptional rates. Second, in all 18 species investigated here, between one and three different regulatory motifs were identified. In 14 of these 18 species, the probability that at least one of these motifs occurred because of the random assortment of bases within the regions investigated was 10% or less. In 12 of these 14 species, the probability was 5% or less. Third, the evolutionary divergence of flatworm species investigated is quite ancient. Therefore, the interspecific distribution of motifs observed here, in a rapidly evolving region such as ITS1, is unlikely to be attributable solely to shared evolutionary histories. These results, therefore, suggest a broader functional role for the ITS1 than previously thought.

  5. ELM 2016—data update and new functionality of the eukaryotic linear motif resource

    PubMed Central

    Dinkel, Holger; Van Roey, Kim; Michael, Sushama; Kumar, Manjeet; Uyar, Bora; Altenberg, Brigitte; Milchevskaya, Vladislava; Schneider, Melanie; Kühn, Helen; Behrendt, Annika; Dahl, Sophie Luise; Damerell, Victoria; Diebel, Sandra; Kalman, Sara; Klein, Steffen; Knudsen, Arne C.; Mäder, Christina; Merrill, Sabina; Staudt, Angelina; Thiel, Vera; Welti, Lukas; Davey, Norman E.; Diella, Francesca; Gibson, Toby J.

    2016-01-01

    The Eukaryotic Linear Motif (ELM) resource (http://elm.eu.org) is a manually curated database of short linear motifs (SLiMs). In this update, we present the latest additions to this resource, along with more improvements to the web interface. ELM 2016 contains more than 240 different motif classes with over 2700 experimentally validated instances, manually curated from more than 2400 scientific publications. In addition, more data have been made available as individually searchable pages and are downloadable in various formats. PMID:26615199

  6. Phosphopeptide interactions with BRCA1 BRCT domains: More than just a motif.

    PubMed

    Wu, Qian; Jubb, Harry; Blundell, Tom L

    2015-03-01

    BRCA1 BRCT domains function as phosphoprotein-binding modules for recognition of the phosphorylated protein-sequence motif pSXXF. While the motif interaction interface provides strong anchor points for binding, protein regions outside the motif have recently been found to be important for binding affinity. In this review, we compare the available structural data for BRCA1 BRCT domains in complex with phosphopeptides in order to gain a more complete understanding of the interaction between phosphopeptides and BRCA1-BRCT domains.

  7. The coxsackievirus A9 RGD motif is not essential for virus viability.

    PubMed Central

    Hughes, P J; Horsnell, C; Hyypiä, T; Stanway, G

    1995-01-01

    An RGD (arginine-glycine-aspartic acid) motif in coxsackievirus A9 has been implicated in internalization through an interaction with the integrin alpha v beta 3. We have produced a number of virus mutants, lacking the motif, which have a small-plaque phenotype in LLC-Mk2 and A-Vero cells and are phenotypically normal in RD cells. Substitution of flanking amino acids also affected plaque size. The results suggest that interaction between the RGD motif and alpha v beta 3 is not critical for virus viability in the cell lines tested and therefore that alternative regions of the CAV-9 capsid are involved in internalization. PMID:7494317

  8. Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators

    PubMed Central

    Yaklichkin, Sergey; Vekker, Alexander; Stayrook, Steven; Lewis, Mitchell; Kessler, Daniel S

    2007-01-01

    Background The Fox gene family comprises a large and functionally diverse group of forkhead-related transcriptional regulators, many of which are essential for metazoan embryogenesis and physiology. Defining conserved functional domains that mediate the transcriptional activity of Fox proteins will contribute to a comprehensive understanding of the biological function of Fox family genes. Results Systematic analysis of 458 protein sequences of the metazoan Fox family was performed to identify the presence of the engrailed homology-1 motif (eh1), a motif known to mediate physical interaction with transcriptional corepressors of the TLE/Groucho family. Greater than 50% of Fox proteins contain sequences with high similarity to the eh1 motif, including ten of the nineteen Fox subclasses (A, B, C, D, E, G, H, I, L, and Q) and Fox proteins of early divergent species such as marine sponge. The eh1 motif is not detected in Fox proteins of the F, J, K, M, N, O, P, R and S subclasses, or in yeast Fox proteins. The eh1-like motifs are positioned C-terminal to the winged helix DNA-binding domain in all subclasses except for FoxG proteins, which have an N-terminal motif. Two similar eh1-like motifs are found in the zebrafish FoxQ1 and in FoxG proteins of sea urchin and amphioxus. The identification of eh1-like motifs by manual sequence alignment was validated by statistical analyses of the Swiss protein database, confirming a high frequency of occurrence of eh1-like sequences in Fox family proteins. Structural predictions suggest that the majority of identified eh1-like motifs are short α-helices, and wheel modeling revealed an amphipathicity that supports this secondary structure prediction. Conclusion A search for eh1 Groucho interaction motifs in the Fox gene family has identified eh1-like sequences in greater than 50% of Fox proteins. The results predict a physical and functional interaction of TLE/Groucho corepressors with many members of the Fox family of transcriptional

  9. Elongated polyproline motifs facilitate enamel evolution through matrix subunit compaction.

    PubMed

    Jin, Tianquan; Ito, Yoshihiro; Luan, Xianghong; Dangaria, Smit; Walker, Cameron; Allen, Michael; Kulkarni, Ashok; Gibson, Carolyn; Braatz, Richard; Liao, Xiubei; Diekwisch, Thomas G H

    2009-12-01

    Vertebrate body designs rely on hydroxyapatite as the principal mineral component of relatively light-weight, articulated endoskeletons and sophisticated tooth-bearing jaws, facilitating rapid movement and efficient predation. Biological mineralization and skeletal growth are frequently accomplished through proteins containing polyproline repeat elements. Through their well-defined yet mobile and flexible structure polyproline-rich proteins control mineral shape and contribute many other biological functions including Alzheimer's amyloid aggregation and prolamine plant storage. In the present study we have hypothesized that polyproline repeat proteins exert their control over biological events such as mineral growth, plaque aggregation, or viscous adhesion by altering the length of their central repeat domain, resulting in dramatic changes in supramolecular assembly dimensions. In order to test our hypothesis, we have used the vertebrate mineralization protein amelogenin as an exemplar and determined the biological effect of the four-fold increased polyproline tandem repeat length in the amphibian/mammalian transition. To study the effect of polyproline repeat length on matrix assembly, protein structure, and apatite crystal growth, we have measured supramolecular assembly dimensions in various vertebrates using atomic force microscopy, tested the effect of protein assemblies on crystal growth by electron microscopy, generated a transgenic mouse model to examine the effect of an abbreviated polyproline sequence on crystal growth, and determined the structure of polyproline repeat elements using 3D NMR. Our study shows that an increase in PXX/PXQ tandem repeat motif length results (i) in a compaction of protein matrix subunit dimensions, (ii) reduced conformational variability, (iii) an increase in polyproline II helices, and (iv) promotion of apatite crystal length. Together, these findings establish a direct relationship between polyproline tandem repeat fragment

  10. Peptoid nanosheets exhibit a new secondary-structure motif

    NASA Astrophysics Data System (ADS)

    Mannige, Ranjan V.; Haxton, Thomas K.; Proulx, Caroline; Robertson, Ellen J.; Battigelli, Alessia; Butterfoss, Glenn L.; Zuckermann, Ronald N.; Whitelam, Stephen

    2015-10-01

    A promising route to the synthesis of protein-mimetic materials that are capable of complex functions, such as molecular recognition and catalysis, is provided by sequence-defined peptoid polymers--structural relatives of biologically occurring polypeptides. Peptoids, which are relatively non-toxic and resistant to degradation, can fold into defined structures through a combination of sequence-dependent interactions. However, the range of possible structures that are accessible to peptoids and other biological mimetics is unknown, and our ability to design protein-like architectures from these polymer classes is limited. Here we use molecular-dynamics simulations, together with scattering and microscopy data, to determine the atomic-resolution structure of the recently discovered peptoid nanosheet, an ordered supramolecular assembly that extends macroscopically in only two dimensions. Our simulations show that nanosheets are structurally and dynamically heterogeneous, can be formed only from peptoids of certain lengths, and are potentially porous to water and ions. Moreover, their formation is enabled by the peptoids' adoption of a secondary structure that is not seen in the natural world. This structure, a zigzag pattern that we call a Σ(`sigma')-strand, results from the ability of adjacent backbone monomers to adopt opposed rotational states, thereby allowing the backbone to remain linear and untwisted. Linear backbones tiled in a brick-like way form an extended two-dimensional nanostructure, the Σ-sheet. The binary rotational-state motif of the Σ-strand is not seen in regular protein structures, which are usually built from one type of rotational state. We also show that the concept of building regular structures from multiple rotational states can be generalized beyond the peptoid nanosheet system.

  11. Elongated Polyproline Motifs Facilitate Enamel Evolution through Matrix Subunit Compaction

    PubMed Central

    Luan, Xianghong; Dangaria, Smit; Walker, Cameron; Allen, Michael; Kulkarni, Ashok; Gibson, Carolyn; Braatz, Richard; Liao, Xiubei; Diekwisch, Thomas G. H.

    2009-01-01

    Vertebrate body designs rely on hydroxyapatite as the principal mineral component of relatively light-weight, articulated endoskeletons and sophisticated tooth-bearing jaws, facilitating rapid movement and efficient predation. Biological mineralization and skeletal growth are frequently accomplished through proteins containing polyproline repeat elements. Through their well-defined yet mobile and flexible structure polyproline-rich proteins control mineral shape and contribute many other biological functions including Alzheimer's amyloid aggregation and prolamine plant storage. In the present study we have hypothesized that polyproline repeat proteins exert their control over biological events such as mineral growth, plaque aggregation, or viscous adhesion by altering the length of their central repeat domain, resulting in dramatic changes in supramolecular assembly dimensions. In order to test our hypothesis, we have used the vertebrate mineralization protein amelogenin as an exemplar and determined the biological effect of the four-fold increased polyproline tandem repeat length in the amphibian/mammalian transition. To study the effect of polyproline repeat length on matrix assembly, protein structure, and apatite crystal growth, we have measured supramolecular assembly dimensions in various vertebrates using atomic force microscopy, tested the effect of protein assemblies on crystal growth by electron microscopy, generated a transgenic mouse model to examine the effect of an abbreviated polyproline sequence on crystal growth, and determined the structure of polyproline repeat elements using 3D NMR. Our study shows that an increase in PXX/PXQ tandem repeat motif length results (i) in a compaction of protein matrix subunit dimensions, (ii) reduced conformational variability, (iii) an increase in polyproline II helices, and (iv) promotion of apatite crystal length. Together, these findings establish a direct relationship between polyproline tandem repeat fragment

  12. [Scanning electron microscopic study of so-called carvable composite filling materials after over one-year functional period].

    PubMed

    Triadan, H

    1979-03-01

    28 class-5 and 16 class-1 fillings were made from the composite material "Epoxydent" on a macaca speciosa monkey and examined with the electron microscope after a 15 months functional period. Statistically significant differences in the size of the marginal space were found to be larger than in comparable composites Adaptic, Concise, Compo-Cap and Cosmic. The spaces were frequently not located on the filling margin but inside, within the filling material. This is attributed to the "carving" technique during the gel phase of setting. The surface shows abrasions and porosities with loss of particles, sometimes fractures and discolored margins with secondary caries. It is not recommended to replace metal fillings by so-called carvable composits.

  13. A variety of DNA-binding and multimeric proteins contain the histone fold motif.

    PubMed Central

    Baxevanis, A D; Arents, G; Moudrianakis, E N; Landsman, D

    1995-01-01

    The histone fold motif has previously been identified as a structural feature common to all four core histones and is involved in both histone-histone and histone-DNA interactions. Through the use of a novel motif searching method, a group of proteins containing the histone fold motif has been established. The proteins in this group are involved in a wide variety of functions related mostly to DNA metabolism. Most of these proteins engage in protein-protein or protein-DNA interactions, as do their core histone counterparts. Among these, CCAAT-specific transcription factor CBF and its yeast homologue HAP are two examples of multimeric complexes with different component subunits that contain the histone fold motif. The histone fold proteins are distantly related, with a relatively small degree of absolute sequence similarity. It is proposed that these proteins may share a similar three-dimensional conformation despite the lack of significant sequence similarity. PMID:7651829

  14. [Proteomic peptide library for determination of substrate motif of casein kinase 2].

    PubMed

    Zhang, Manyu; Wang, Chunli; Bian, Yangyang; Cheng, Kai; Wei, Xiaoluan; Ye, Mingliang; Zou, Hanfa

    2011-08-01

    Substrate motif is of great importance in kinase-substrate recognition and contributes a lot to the understanding of signal transduction. In this study, a proteomic peptide library was generated to determine substrate motif of casein kinase 2. Firstly, whole cell lysate was digested by trypsin to generate a large number of candidate peptides, which were then incubated with alkaline phosphotase to dephosphorylate intrinsic phosphopeptides. Then, the unphosphorylated peptide mixture was incubated with casein kinase 2 (CK2) and adenosine-triphosphate (ATP) for 30 min, and the resulting phosphopeptides were enriched by immobilized metal affinity chromatography (IMAC) followed by reversed-phase liquid chromatographic separation coupled with tandem mass spectrometry detection. Finally, the 472 unique phosphopeptides and 451 unique phosphorylation sites were identified, resulting in the determination of a motif of S/T-D/E-x-D/E for CK2. This method enables accurate determination of substrate motif in a short time and can be readily applied to other kinases.

  15. A motif rich in charged residues determines product specificity in isomaltulose synthase.

    PubMed

    Zhang, Daohai; Li, Nan; Swaminathan, Kunchithapadam; Zhang, Lian Hui

    2003-01-16

    Isomaltulose synthase (PalI) catalyzes hydrolysis of sucrose and formation of alpha-1,6 and alpha-1,1 bonds to produce isomaltulose (alpha-D-glucosylpyranosyl-1,6-D-fructofranose) and small amount of trehalulose (alpha-D-glucosylpyranosyl-1,1-D-fructofranose). A potential isomaltulose synthase-specific motif ((325)RLDRD(329)), that contains a 'DxD' motif conserved in many glycosyltransferases, was identified based on sequence comparison with reference to the secondary structural features of PalI and homologs. Site-directed mutagenesis analysis of the motif showed that the four charged amino acid residues (Arg(325), Arg(328), Asp(327) and Asp(329)) influence the enzyme kinetics and determine the product specificity. Mutation of these four residues increased trehalulose formation by 17-61% and decreased isomaltulose by 26-67%. We conclude that the 'RLDRD' motif controls the product specificity of PalI.

  16. Multi-scale modularity and motif distributional effect in metabolic networks.

    PubMed

    Gao, Shang; Chen, Alan; Rahmani, Ali; Zeng, Jia; Tan, Mehmet; Alhajj, Reda; Rokne, Jon; Demetrick, Douglas; Wei, Xiaohui

    2016-01-01

    Metabolism is a set of fundamental processes that play important roles in a plethora of biological and medical contexts. It is understood that the topological information of reconstructed metabolic networks, such as modular organization, has crucial implications on biological functions. Recent interpretations of modularity in network settings provide a view of multiple network partitions induced by different resolution parameters. Here we ask the question: How do multiple network partitions affect the organization of metabolic networks? Since network motifs are often interpreted as the super families of evolved units, we further investigate their impact under multiple network partitions and investigate how the distribution of network motifs influences the organization of metabolic networks. We studied Homo sapiens, Saccharomyces cerevisiae and Escherichia coli metabolic networks; we analyzed the relationship between different community structures and motif distribution patterns. Further, we quantified the degree to which motifs participate in the modular organization of metabolic networks.

  17. Understanding eukaryotic linear motifs and their role in cell signaling and regulation.

    PubMed

    Diella, Francesca; Haslam, Niall; Chica, Claudia; Budd, Aidan; Michael, Sushama; Brown, Nigel P; Trave, Gilles; Gibson, Toby J

    2008-05-01

    It is now clear that a detailed picture of cell regulation requires a comprehensive understanding of the abundant short protein motifs through which signaling is channeled. The current body of knowledge has slowly accumulated through piecemeal experimental investigation of individual motifs in signaling. Computational methods contributed little to this process. A new generation of bioinformatics tools will aid the future investigation of motifs in regulatory proteins, and the disordered polypeptide regions in which they frequently reside. Allied to high throughput methods such as phosphoproteomics, signaling networks are becoming amenable to experimental deconstruction. In this review, we summarise the current state of linear motif biology, which uses low affinity interactions to create cooperative, combinatorial and highly dynamic regulatory protein complexes. The discrete deterministic properties implicit to these assemblies suggest that models for cell regulatory networks in systems biology should neither be overly dependent on stochastic nor on smooth deterministic approximations.

  18. The role of the fibronectin IGD motif in stimulating fibroblast migration.

    PubMed

    Millard, Christopher J; Ellis, Ian R; Pickford, Andrew R; Schor, Ana M; Schor, Seth L; Campbell, Iain D

    2007-12-07

    The motogenic activity of migration-stimulating factor, a truncated isoform of fibronectin (FN), has been attributed to the IGD motifs present in its FN type 1 modules. The structure-function relationship of various recombinant IGD-containing FN fragments is now investigated. Their structure is assessed by solution state NMR and their motogenic ability tested on fibroblasts. Even conservative mutations in the IGD motif are inactive or have severely reduced potency, while the structure remains essentially the same. A fragment with two IGD motifs is 100 times more active than a fragment with one and up to 10(6) times more than synthetic tetrapeptides. The wide range of potency in different contexts is discussed in terms of cryptic FN sites and cooperativity. These results give new insight into the stimulation of fibroblast migration by IGD motifs in FN.

  19. DNA motifs determining the accuracy of repeat duplication during CRISPR adaptation in Haloarcula hispanica

    PubMed Central

    Wang, Rui; Li, Ming; Gong, Luyao; Hu, Songnian; Xiang, Hua

    2016-01-01

    Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) acquire new spacers to generate adaptive immunity in prokaryotes. During spacer integration, the leader-preceded repeat is always accurately duplicated, leading to speculations of a repeat-length ruler. Here in Haloarcula hispanica, we demonstrate that the accurate duplication of its 30-bp repeat requires two conserved mid-repeat motifs, AACCC and GTGGG. The AACCC motif was essential and needed to be ∼10 bp downstream from the leader-repeat junction site, where duplication consistently started. Interestingly, repeat duplication terminated sequence-independently and usually with a specific distance from the GTGGG motif, which seemingly served as an anchor site for a molecular ruler. Accordingly, altering the spacing between the two motifs led to an aberrant duplication size (29, 31, 32 or 33 bp). We propose the adaptation complex may recognize these mid-repeat elements to enable measuring the repeat DNA for spacer integration. PMID:27085805

  20. Circular code motifs in transfer and 16S ribosomal RNAs: a possible translation code in genes.

    PubMed

    Michel, Christian J

    2012-04-01

    In 1996, a common trinucleotide circular code, called X, is identified in genes of eukaryotes and prokaryotes (Arquès and Michel, 1996). This circular code X is a set of 20 trinucleotides allowing the reading frames in genes to be retrieved locally, i.e. anywhere in genes and in particular without start codons. This reading frame retrieval needs a window length l of 12 nucleotides (l ≥ 12). With a window length strictly less than 12 nucleotides (l < 12), some words of X, called ambiguous words, are found in the shifted frames (the reading frame shifted by one or two nucleotides) preventing the reading frame in genes to be retrieved. Since 1996, these ambiguous words of X were never studied. In the first part of this paper, we identify all the ambiguous words of the common trinucleotide circular code X. With a length l varying from 1 to 11 nucleotides, the type and the occurrence number (multiplicity) of ambiguous words of X are given in each shifted frame. Maximal ambiguous words of X, words which are not factors of another ambiguous words, are also determined. Two probability definitions based on these results show that the common trinucleotide circular code X retrieves the reading frame in genes with a probability of about 90% with a window length of 6 nucleotides, and a probability of 99.9% with a window length of 9 nucleotides (100% with a window length of 12 nucleotides, by definition of a circular code). In the second part of this paper, we identify X circular code motifs (shortly X motifs) in transfer RNA and 16S ribosomal RNA: a tRNA X motif of 26 nucleotides including the anticodon stem-loop and seven 16S rRNA X motifs of length greater or equal to 15 nucleotides. Window lengths of reading frame retrieval with each trinucleotide of these X motifs are also determined. Thanks to the crystal structure 3I8G (Jenner et al., 2010), a 3D visualization of X motifs in the ribosome shows several spatial configurations involving mRNA X motifs, A-tRNA and E-tRNA X

  1. Computational discovery of cis-regulatory modules in Drosophila without prior knowledge of motifs

    PubMed Central

    Ivan, Andra; Halfon, Marc S; Sinha, Saurabh

    2008-01-01

    We consider the problem of predicting cis-regulatory modules without knowledge of motifs. We formulate this problem in a pragmatic setting, and create over 30 new data sets, using Drosophila modules, to use as a 'benchmark'. We propose two new methods for the problem, and evaluate these, as well as two existing methods, on our benchmark. We find that the challenge of predicting cis-regulatory modules ab initio, without any input of relevant motifs, is a realizable goal. PMID:18226245

  2. A novel approach to identifying regulatory motifs in distantly related genomes

    PubMed Central

    Van Hellemont, Ruth; Monsieurs, Pieter; Thijs, Gert; De Moor, Bart; Van de Peer, Yves; Marchal, Kathleen

    2005-01-01

    Although proven successful in the identification of regulatory motifs, phylogenetic footprinting methods still show some shortcomings. To assess these difficulties, most apparent when applying phylogenetic footprinting to distantly related organisms, we developed a two-step procedure that combines the advantages of sequence alignment and motif detection approaches. The results on well-studied benchmark datasets indicate that the presented method outperforms other methods when the sequences become either too long or too heterogeneous in size. PMID:16420672

  3. CytoKavosh: A Cytoscape Plug-In for Finding Network Motifs in Large Biological Networks

    PubMed Central

    Razaghi Moghadam Kashani, Zahra; Salehzadeh-Yazdi, Ali; Khakabimamaghani, Sahand

    2012-01-01

    Network motifs are small connected sub-graphs that have recently gathered much attention to discover structural behaviors of large and complex networks. Finding motifs with any size is one of the most important problems in complex and large networks. It needs fast and reliable algorithms and tools for achieving this purpose. CytoKavosh is one of the best choices for finding motifs with any given size in any complex network. It relies on a fast algorithm, Kavosh, which makes it faster than other existing tools. Kavosh algorithm applies some well known algorithmic features and includes tricky aspects, which make it an efficient algorithm in this field. CytoKavosh is a Cytoscape plug-in which supports us in finding motifs of given size in a network that is formerly loaded into the Cytoscape work-space (directed or undirected). High performance of CytoKavosh is achieved by dynamically linking highly optimized functions of Kavosh's C++ to the Cytoscape Java program, which makes this plug-in suitable for analyzing large biological networks. Some significant attributes of CytoKavosh is efficiency in time usage and memory and having no limitation related to the implementation in motif size. CytoKavosh is implemented in a visual environment Cytoscape that is convenient for the users to interact and create visual options to analyze the structural behavior of a network. This plug-in can work on any given network and is very simple to use and generates graphical results of discovered motifs with any required details. There is no specific Cytoscape plug-in, specific for finding the network motifs, based on original concept. So, we have introduced for the first time, CytoKavosh as the first plug-in, and we hope that this plug-in can be improved to cover other options to make it the best motif-analyzing tool. PMID:22952659

  4. Excluded volume effects on the kinetic assembling of a structural motif for RNA catalysis

    NASA Astrophysics Data System (ADS)

    Fernández, Ariel

    1991-09-01

    We establish the role of excluded volume effects on the loss of conformational entropy due to pseudoknot formation in RNA. This pseudoknot appears to be the structural motif responsible for shaping the splicing site of certain noncoding RNA transcriptional products. Focusing on the illustrative example of the YC4 intron, we show that the emergence of this motif is kinetically driven and prevails over competing catalytically inert secondary structure due to excluded volume effects which favor the correlation of interacting intramolecular loops.

  5. Molecular Signaling Network Motifs Provide a Mechanistic Basis for Cellular Threshold Responses

    PubMed Central

    Bhattacharya, Sudin; Conolly, Rory B.; Clewell, Harvey J.; Kaminski, Norbert E.; Andersen, Melvin E.

    2014-01-01

    Background: Increasingly, there is a move toward using in vitro toxicity testing to assess human health risk due to chemical exposure. As with in vivo toxicity testing, an important question for in vitro results is whether there are thresholds for adverse cellular responses. Empirical evaluations may show consistency with thresholds, but the main evidence has to come from mechanistic considerations. Objectives: Cellular response behaviors depend on the molecular pathway and circuitry in the cell and the manner in which chemicals perturb these circuits. Understanding circuit structures that are inherently capable of resisting small perturbations and producing threshold responses is an important step towards mechanistically interpreting in vitro testing data. Methods: Here we have examined dose–response characteristics for several biochemical network motifs. These network motifs are basic building blocks of molecular circuits underpinning a variety of cellular functions, including adaptation, homeostasis, proliferation, differentiation, and apoptosis. For each motif, we present biological examples and models to illustrate how thresholds arise from specific network structures. Discussion and Conclusion: Integral feedback, feedforward, and transcritical bifurcation motifs can generate thresholds. Other motifs (e.g., proportional feedback and ultrasensitivity)produce responses where the slope in the low-dose region is small and stays close to the baseline. Feedforward control may lead to nonmonotonic or hormetic responses. We conclude that network motifs provide a basis for understanding thresholds for cellular responses. Computational pathway modeling of these motifs and their combinations occurring in molecular signaling networks will be a key element in new risk assessment approaches based on in vitro cellular assays. Citation: Zhang Q, Bhattacharya S, Conolly RB, Clewell HJ III, Kaminski NE, Andersen ME. 2014. Molecular signaling network motifs provide a

  6. CXC motif chemokine receptor 4 gene polymorphism and cancer risk

    PubMed Central

    Wu, Yang; Zhang, Chun; Xu, Weizhang; Zhang, Jianzhong; Zheng, Yuxiao; Lu, Zipeng; Liu, Dongfang; Jiang, Kuirong

    2016-01-01

    Abstract Background: Previous epidemiological studies have reported the relationship between CXC motif chemokine receptor 4 (CXCR4) synonymous polymorphism (rs2228014), and risk of cancer, but the results remained conflicting and controversial. Therefore, this study was devised to evaluate the genetic effects of the rs2228014 polymorphism on cancer risk in a large meta-analysis. Methods: The computer-based databases (EMBASE, Web of Science, and PubMed) were searched for all relevant studies evaluating rs2228014 and susceptibility to cancer. In the analysis, pooled odds ratios (ORs) with its corresponding 95% confidence intervals (CIs) were calculated in 5 genetic models to assess the genetic risk. Egger regression and Begg funnel plots test were conducted to appraise the publication bias. Results: Data on rs2228014 polymorphism and overall cancer risk were available for 3684 cancer patients and 5114 healthy controls participating in 11 studies. Overall, a significantly increased risk of cancer was associated with rs2228014 polymorphism in homozygote model (OR = 2.01, 95% CI: 1.22–3.33) and in recessive model (OR = 1.97, 95% CI: 1.23–3.16). When stratified by ethnicity, the results were positive only in Asian populations (heterozygote model: OR = 1.36, 95% CI: 1.13–1.65; homozygote model: OR = 2.43, 95% CI: 1.21–4.91; dominant model: OR = 1.47, 95% CI: 1.13–1.90; recessive model: OR = 2.25, 95% CI: 1.13–4.48; and allele model: OR = 1.48, 95% CI: 1.10–1.99). Besides, in the subgroup analysis by source of control, the result was significant only in population-based control (homozygote model: OR = 2.39, 95% CI: 1.06–5.40; recessive model: pooled OR = 2.24, 95% CI: 1.02–4.96). Conclusion: In general, our results first indicated that the rs2228014 polymorphism in CXCR4 gene is correlated with an increased risk of cancer, especially among Asian ethnicity. Large, well-designed epidemiological studies are required to verify the current findings. PMID

  7. Fast revelation of the motif mode for a yeast protein interaction network through intelligent agent-based distributed computing.

    PubMed

    Lee, Wei-Po; Tzou, Wen-Shyong

    2010-09-01

    In the yeast protein-protein interaction network, motif mode, a collection of motifs of special combinations of protein nodes annotated by the molecular function terms of the Gene Ontology, has revealed differences in the conservation constraints within the same topology. In this study, by employing an intelligent agent-based distributed computing method, we are able to discover motif modes in a fast and adaptive manner. Moreover, by focusing on the highly evolutionarily conserved motif modes belonging to the same biological function, we find a large downshift in the distance between nodes belonging to the same motif mode compared with the whole, suggesting that nodes with the same motif mode tend to congregate in a network. Several motif modes with a high conservation of the motif constituents were revealed, but from a new perspective, including that with a three-node motif mode engaged in the protein fate and that with three four-node motif modes involved in the genome maintenance, cellular organization, and transcription. The network motif modes discovered from this method can be linked to the wealth of biological data which require further elucidation with regard to biological functions.

  8. How to find a leucine in a haystack? Structure, ligand recognition and regulation of leucine-aspartic acid (LD) motifs.

    PubMed

    Alam, Tanvir; Alazmi, Meshari; Gao, Xin; Arold, Stefan T

    2014-06-15

    LD motifs (leucine-aspartic acid motifs) are short helical protein-protein interaction motifs that have emerged as key players in connecting cell adhesion with cell motility and survival. LD motifs are required for embryogenesis, wound healing and the evolution of multicellularity. LD motifs also play roles in disease, such as in cancer metastasis or viral infection. First described in the paxillin family of scaffolding proteins, LD motifs and similar acidic LXXLL interaction motifs have been discovered in several other proteins, whereas 16 proteins have been reported to contain LDBDs (LD motif-binding domains). Collectively, structural and functional analyses have revealed a surprising multivalency in LD motif interactions and a wide diversity in LDBD architectures. In the present review, we summarize the molecular basis for function, regulation and selectivity of LD motif interactions that has emerged from more than a decade of research. This overview highlights the intricate multi-level regulation and the inherently noisy and heterogeneous nature of signalling through short protein-protein interaction motifs.

  9. DRIMust: a web server for discovering rank imbalanced motifs using suffix trees

    PubMed Central

    Leibovich, Limor; Paz, Inbal; Yakhini, Zohar; Mandel-Gutfreund, Yael

    2013-01-01

    Cellular regulation mechanisms that involve proteins and other active molecules interacting with specific targets often involve the recognition of sequence patterns. Short sequence elements on DNA, RNA and proteins play a central role in mediating such molecular recognition events. Studies that focus on measuring and investigating sequence-based recognition processes make use of statistical and computational tools that support the identification and understanding of sequence motifs. We present a new web application, named DRIMust, freely accessible through the website http://drimust.technion.ac.il for de novo motif discovery services. The DRIMust algorithm is based on the minimum hypergeometric statistical framework and uses suffix trees for an efficient enumeration of motif candidates. DRIMust takes as input ranked lists of sequences in FASTA format and returns motifs that are over-represented at the top of the list, where the determination of the threshold that defines top is data driven. The resulting motifs are presented individually with an accurate P-value indication and as a Position Specific Scoring Matrix. Comparing DRIMust with other state-of-the-art tools demonstrated significant advantage to DRIMust, both in result accuracy and in short running times. Overall, DRIMust is unique in combining efficient search on large ranked lists with rigorous P-value assessment for the detected motifs. PMID:23685432

  10. An analysis of multi-type relational interactions in FMA using graph motifs with disjointness constraints.

    PubMed

    Zhang, Guo-Qiang; Luo, Lingyun; Ogbuji, Chime; Joslyn, Cliff; Mejino, Jose; Sahoo, Satya S

    2012-01-01

    The interaction of multiple types of relationships among anatomical classes in the Foundational Model of Anatomy (FMA) can provide inferred information valuable for quality assurance. This paper introduces a method called Motif Checking (MOCH) to study the effects of such multi-relation type interactions for detecting logical inconsistencies as well as other anomalies represented by the motifs. MOCH represents patterns of multi-type interaction as small labeled (with multiple types of edges) sub-graph motifs, whose nodes represent class variables, and labeled edges represent relational types. By representing FMA as an RDF graph and motifs as SPARQL queries, fragments of FMA are automatically obtained as auditing candidates. Leveraging the scalability and reconfigurability of Semantic Web Technology, we performed exhaustive analyses of a variety of labeled sub-graph motifs. The quality assurance feature of MOCH comes from the distinct use of a subset of the edges of the graph motifs as constraints for disjointness, whereby bringing in rule-based flavor to the approach as well. With possible disjointness implied by antonyms, we performed manual inspection of the resulting FMA fragments and tracked down sources of abnormal inferred conclusions (logical inconsistencies), which are amendable for programmatic revision of the FMA. Our results demonstrate that MOCH provides a unique source of valuable information for quality assurance. Since our approach is general, it is applicable to any ontological system with an OWL representation.

  11. DRIMust: a web server for discovering rank imbalanced motifs using suffix trees.

    PubMed

    Leibovich, Limor; Paz, Inbal; Yakhini, Zohar; Mandel-Gutfreund, Yael

    2013-07-01

    Cellular regulation mechanisms that involve proteins and other active molecules interacting with specific targets often involve the recognition of sequence patterns. Short sequence elements on DNA, RNA and proteins play a central role in mediating such molecular recognition events. Studies that focus on measuring and investigating sequence-based recognition processes make use of statistical and computational tools that support the identification and understanding of sequence motifs. We present a new web application, named DRIMust, freely accessible through the website http://drimust.technion.ac.il for de novo motif discovery services. The DRIMust algorithm is based on the minimum hypergeometric statistical framework and uses suffix trees for an efficient enumeration of motif candidates. DRIMust takes as input ranked lists of sequences in FASTA format and returns motifs that are over-represented at the top of the list, where the determination of the threshold that defines top is data driven. The resulting motifs are presented individually with an accurate P-value indication and as a Position Specific Scoring Matrix. Comparing DRIMust with other state-of-the-art tools demonstrated significant advantage to DRIMust, both in result accuracy and in short running times. Overall, DRIMust is unique in combining efficient search on large ranked lists with rigorous P-value assessment for the detected motifs.

  12. Identification of disease-specific motifs in the antibody specificity repertoire via next-generation sequencing

    PubMed Central

    Pantazes, Robert J.; Reifert, Jack; Bozekowski, Joel; Ibsen, Kelly N.; Murray, Joseph A.; Daugherty, Patrick S.

    2016-01-01

    Disease-specific antibodies can serve as highly effective biomarkers but have been identified for only a relatively small number of autoimmune diseases. A method was developed to identify disease-specific binding motifs through integration of bacterial display peptide library screening, next-generation sequencing (NGS) and computational analysis. Antibody specificity repertoires were determined by identifying bound peptide library members for each specimen using cell sorting and performing NGS. A computational algorithm, termed Identifying Motifs Using Next- generation sequencing Experiments (IMUNE), was developed and applied to discover disease- and healthy control-specific motifs. IMUNE performs comprehensive pattern searches, identifies patterns statistically enriched in the disease or control groups and clusters the patterns to generate motifs. Using celiac disease sera as a discovery set, IMUNE identified a consensus motif (QPEQPF[PS]E) with high diagnostic sensitivity and specificity in a validation sera set, in addition to novel motifs. Peptide display and sequencing (Display-Seq) coupled with IMUNE analysis may thus be useful to characterize antibody repertoires and identify disease-specific antibody epitopes and biomarkers. PMID:27481573

  13. What Determines the Assembly of Transcriptional Network Motifs in Escherichia coli?

    PubMed Central

    Camas, Francisco M.; Poyatos, Juan F.

    2008-01-01

    Transcriptional networks are constituted by a collection of building blocks known as network motifs. Why do motifs appear? An adaptive model of motif emergence was recently questioned in favor of neutralist scenarios. Here, we provide a new picture of motif assembly in Escherichia coli which partially clarifies these contrasting explanations. This is based on characterizing the linkage between motifs and sensing or response specificity of their constituent transcriptional factors (TFs). We find that sensing specificity influences the distribution of autoregulation, while the tendency of a TF to establish feed-forward loops (FFLs) depends on response specificity, i.e., regulon size. Analysis of the latter pattern reveals that coregulation between large regulon-size TFs is common under a network neutral model, leading to the assembly of a great number of FFLs and bifans. In addition, neutral exclusive regulation also leads to a collection of single input modules -the fourth basic motif. On the whole, and even under the conservative neutralist scenario considered, a substantial group of regulatory structures revealed adaptive. These structures visibly function as fully-fledged working units. PMID:18987754

  14. Predicting candidate genomic sequences that correspond to synthetic functional RNA motifs

    PubMed Central

    Laserson, Uri; Gan, Hin Hark; Schlick, Tamar

    2005-01-01

    Riboswitches and RNA interference are important emerging mechanisms found in many organisms to control gene expression. To enhance our understanding of such RNA roles, finding small regulatory motifs in genomes presents a challenge on a wide scale. Many simple functional RNA motifs have been found by in vitro selection experiments, which produce synthetic target-binding aptamers as well as catalytic RNAs, including the hammerhead ribozyme. Motivated by the prediction of Piganeau and Schroeder [(2003) Chem. Biol., 10, 103–104] that synthetic RNAs may have natural counterparts, we develop and apply an efficient computational protocol for identifying aptamer-like motifs in genomes. We define motifs from the sequence and structural information of synthetic aptamers, search for sequences in genomes that will produce motif matches, and then evaluate the structural stability and statistical significance of the potential hits. Our application to aptamers for streptomycin, chloramphenicol, neomycin B and ATP identifies 37 candidate sequences (in coding and non-coding regions) that fold to the target aptamer structures in bacterial and archaeal genomes. Further energetic screening reveals that several candidates exhibit energetic properties and sequence conservation patterns that are characteristic of functional motifs. Besides providing candidates for experimental testing, our computational protocol offers an avenue for expanding natural RNA's functional repertoire. PMID:16254081

  15. Artefacts in statistical analyses of network motifs: general framework and application to metabolic networks.

    PubMed

    Beber, Moritz Emanuel; Fretter, Christoph; Jain, Shubham; Sonnenschein, Nikolaus; Müller-Hannemann, Matthias; Hütt, Marc-Thorsten

    2012-12-07

    Few-node subgraphs are the smallest collective units in a network that can be investigated. They are beyond the scale of individual nodes but more local than, for example, communities. When statistically over- or under-represented, they are called network motifs. Network motifs have been interpreted as building blocks that shape the dynamic behaviour of networks. It is this promise of potentially explaining emergent properties of complex systems with relatively simple structures that led to an interest in network motifs in an ever-growing number of studies and across disciplines. Here, we discuss artefacts in the analysis of network motifs arising from discrepancies between the network under investigation and the pool of random graphs serving as a null model. Our aim was to provide a clear and accessible catalogue of such incongruities and their effect on the motif signature. As a case study, we explore the metabolic network of Escherichia coli and show that only by excluding ever more artefacts from the motif signature a strong and plausible correlation with the essentiality profile of metabolic reactions emerges.

  16. Artefacts in statistical analyses of network motifs: general framework and application to metabolic networks

    PubMed Central

    Beber, Moritz Emanuel; Fretter, Christoph; Jain, Shubham; Sonnenschein, Nikolaus; Müller-Hannemann, Matthias; Hütt, Marc-Thorsten

    2012-01-01

    Few-node subgraphs are the smallest collective units in a network that can be investigated. They are beyond the scale of individual nodes but more local than, for example, communities. When statistically over- or under-represented, they are called network motifs. Network motifs have been interpreted as building blocks that shape the dynamic behaviour of networks. It is this promise of potentially explaining emergent properties of complex systems with relatively simple structures that led to an interest in network motifs in an ever-growing number of studies and across disciplines. Here, we discuss artefacts in the analysis of network motifs arising from discrepancies between the network under investigation and the pool of random graphs serving as a null model. Our aim was to provide a clear and accessible catalogue of such incongruities and their effect on the motif signature. As a case study, we explore the metabolic network of Escherichia coli and show that only by excluding ever more artefacts from the motif signature a strong and plausible correlation with the essentiality profile of metabolic reactions emerges. PMID:22896565

  17. Conservation defines functional motifs in the squint/nodal-related 1 RNA dorsal localization element

    PubMed Central

    Gilligan, Patrick C.; Kumari, Pooja; Lim, Shimin; Cheong, Albert; Chang, Alex; Sampath, Karuna

    2011-01-01

    RNA localization is emerging as a general principle of sub-cellular protein localization and cellular organization. However, the sequence and structural requirements in many RNA localization elements remain poorly understood. Whereas transcription factor-binding sites in DNA can be recognized as short degenerate motifs, and consensus binding sites readily inferred, protein-binding sites in RNA often contain structural features, and can be difficult to infer. We previously showed that zebrafish squint/nodal-related 1 (sqt/ndr1) RNA localizes to the future dorsal side of the embryo. Interestingly, mammalian nodal RNA can also localize to dorsal when injected into zebrafish embryos, suggesting that the sequence motif(s) may be conserved, even though the fish and mammal UTRs cannot be aligned. To define potential sequence and structural features, we obtained ndr1 3′-UTR sequences from approximately 50 fishes that are closely, or distantly, related to zebrafish, for high-resolution phylogenetic footprinting. We identify conserved sequence and structural motifs within the zebrafish/carp family and catfish. We find that two novel motifs, a single-stranded AGCAC motif and a small stem-loop, are required for efficient sqt RNA localization. These findings show that comparative sequencing in the zebrafish/carp family is an efficient approach for identifying weak consensus binding sites for RNA regulatory proteins. PMID:21149265

  18. RNA Bricks—a database of RNA 3D motifs and their interactions

    PubMed Central

    Chojnowski, Grzegorz; Waleń, Tomasz; Bujnicki, Janusz M.

    2014-01-01

    The RNA Bricks database (http://iimcb.genesilico.pl/rnabricks), stores information about recurrent RNA 3D motifs and their interactions, found in experimentally determined RNA structures and in RNA–protein complexes. In contrast to other similar tools (RNA 3D Motif Atlas, RNA Frabase, Rloom) RNA motifs, i.e. ‘RNA bricks’ are presented in the molecular environment, in which they were determined, including RNA, protein, metal ions, water molecules and ligands. All nucleotide residues in RNA bricks are annotated with structural quality scores that describe real-space correlation coefficients with the electron density data (if available), backbone geometry and possible steric conflicts, which can be used to identify poorly modeled residues. The database is also equipped with an algorithm for 3D motif search and comparison. The algorithm compares spatial positions of backbone atoms of the user-provided query structure and of stored RNA motifs, without relying on sequence or secondary structure information. This enables the identification of local structural similarities among evolutionarily related and unrelated RNA molecules. Besides, the search utility enables searching ‘RNA bricks’ according to sequence similarity, and makes it possible to identify motifs with modified ribonucleotide residues at specific positions. PMID:24220091

  19. Distribution of SR protein exonic splicing enhancer motifs in human protein-coding genes.

    PubMed

    Wang, Jinhua; Smith, Philip J; Krainer, Adrian R; Zhang, Michael Q

    2005-01-01

    Exonic splicing enhancers (ESEs) are pre-mRNA cis-acting elements required for splice-site recognition. We previously developed a web-based program called ESEfinder that scores any sequence for the presence of ESE motifs recognized by the human SR proteins SF2/ASF, SRp40, SRp55 and SC35 (http://rulai.cshl.edu/tools/ESE/). Using ESEfinder, we have undertaken a large-scale analysis of ESE motif distribution in human protein-coding genes. Significantly higher frequencies of ESE motifs were observed in constitutive internal protein-coding exons, compared with both their flanking intronic regions and with pseudo exons. Statistical analysis of ESE motif frequency distributions revealed a complex relationship between splice-site strength and increased or decreased frequencies of particular SR protein motifs. Comparison of constitutively and alternatively spliced exons demonstrated slightly weaker splice-site scores, as well as significantly fewer ESE motifs, in the alternatively spliced group. Our results underline the importance of ESE-mediated SR protein function in the process of exon definition, in the context of both constitutive splicing and regulated alternative splicing.

  20. Zinc finger binding motifs do not explain recombination rate variation within or between species of Drosophila.

    PubMed

    Heil, Caiti S S; Noor, Mohamed A F

    2012-01-01

    In humans and mice, the Cys(2)His(2) zinc finger protein PRDM9 binds to a DNA sequence motif enriched in hotspots of recombination, possibly modifying nucleosomes, and recruiting recombination machinery to initiate Double Strand Breaks (DSBs). However, since its discovery, some researchers have suggested that the recombinational effect of PRDM9 is lineage or species specific. To test for a conserved role of PRDM9-like proteins across taxa, we use the Drosophila pseudoobscura species group in an attempt to identify recombination associated zinc finger proteins and motifs. We leveraged the conserved amino acid motifs in Cys(2)His(2) zinc fingers to predict nucleotide binding motifs for all Cys(2)His(2) zinc finger proteins in Drosophila pseudoobscura and identified associations with empirical measures of recombination rate. Additionally, we utilized recombination maps from D. pseudoobscura and D. miranda to explore whether changes in the binding motifs between species can account for changes in the recombination landscape, analogous to the effect observed in PRDM9 among human populations. We identified a handful of potential recombination-associated sequence motifs, but the associations are generally tenuous and their biological relevance remains uncertain. Furthermore, we found no evidence that changes in zinc finger DNA binding explains variation in recombination rate between species. We therefore conclude that there is no protein with a DNA sequence specific human-PRDM9-like function in Drosophila. We suggest these findings could be explained by the existence of a different recombination initiation system in Drosophila.

  1. A systematic approach to identify functional motifs within vertebrate developmental enhancers

    PubMed Central

    Li, Qiang; Ritter, Deborah; Yang, Nan; Dong, Zhiqiang; Li, Hao; Chuang, Jeffrey H.; Guo, Su

    2012-01-01

    Uncovering the cis-regulatory logic of developmental enhancers is critical to understanding the role of non-coding DNA in development. However, it is cumbersome to identify functional motifs within enhancers, and thus few vertebrate enhancers have their core functional motifs revealed. Here we report a combined experimental and computational approach for discovering regulatory motifs in developmental enhancers. Making use of the zebrafish gene expression database, we computationally identified conserved non-coding elements (CNEs) likely to have a desired tissue-specificity based on the expression of nearby genes. Through a high throughput and robust enhancer assay, we tested the activity of ~100 such CNEs and efficiently uncovered developmental enhancers with desired spatial and temporal expression patterns in the zebrafish brain. Application of de novo motif prediction algorithms on a group of forebrain enhancers identified five top-ranked motifs, all of which were experimentally validated as critical for forebrain enhancer activity. These results demonstrate a systematic approach to discover important regulatory motifs in vertebrate developmental enhancers. Moreover, this dataset provides a useful resource for further dissection of vertebrate brain development and function. PMID:19850031

  2. Creation of Hybrid Nanorods From Sequences of Natural Trimeric Fibrous Proteins Using the Fibritin Trimerization Motif

    NASA Astrophysics Data System (ADS)

    Papanikolopoulou, Katerina; van Raaij, Mark J.; Mitraki, Anna

    Stable, artificial fibrous proteins that can be functionalized open new avenues in fields such as bionanomaterials design and fiber engineering. An important source of inspiration for the creation of such proteins are natural fibrous proteins such as collagen, elastin, insect silks, and fibers from phages and viruses. The fibrous parts of this last class of proteins usually adopt trimeric, β-stranded structural folds and are appended to globular, receptor-binding domains. It has been recently shown that the globular domains are essential for correct folding and trimerization and can be successfully substituted by a very small (27-amino acid) trimerization motif from phage T4 fibritin. The hybrid proteins are correctly folded nanorods that can withstand extreme conditions. When the fibrous part derives from the adenovirus fiber shaft, different tissue-targeting specificities can be engineered into the hybrid proteins, which therefore can be used as gene therapy vectors. The integration of such stable nanorods in devices is also a big challenge in the field of biomechanical design. The fibritin foldon domain is a versatile trimerization motif and can be combined with a variety of fibrous motifs, such as coiled-coil, collagenous, and triple β-stranded motifs, provided the appropriate linkers are used. The combination of different motifs within the same fibrous molecule to create stable rods with multiple functions can even be envisioned. We provide a comprehensive overview of the experimental procedures used for designing, creating, and characterizing hybrid fibrous nanorods using the fibritin trimerization motif.

  3. Identifying the preferred RNA motifs and chemotypes that interact by probing millions of combinations.

    PubMed

    Tran, Tuan; Disney, Matthew D

    2012-01-01

    RNA is an important therapeutic target but information about RNA-ligand interactions is limited. Here, we report a screening method that probes over 3,000,000 combinations of RNA motif-small molecule interactions to identify the privileged RNA structures and chemical spaces that interact. Specifically, a small molecule library biased for binding RNA was probed for binding to over 70,000 unique RNA motifs in a high throughput solution-based screen. The RNA motifs that specifically bind each small molecule were identified by microarray-based selection. In this library-versus-library or multidimensional combinatorial screening approach, hairpin loops (among a variety of RNA motifs) were the preferred RNA motif space that binds small molecules. Furthermore, it was shown that indole, 2-phenyl indole, 2-phenyl benzimidazole and pyridinium chemotypes allow for specific recognition of RNA motifs. As targeting RNA with small molecules is an extremely challenging area, these studies provide new information on RNA-ligand interactions that has many potential uses.

  4. Leveraging cross-link modification events in CLIP-seq for motif discovery.

    PubMed

    Bahrami-Samani, Emad; Penalva, Luiz O F; Smith, Andrew D; Uren, Philip J

    2015-01-01

    High-throughput protein-RNA interaction data generated by CLIP-seq has provided an unprecedented depth of access to the activities of RNA-binding proteins (RBPs), the key players in co- and post-transcriptional regulation of gene expression. Motif discovery forms part of the necessary follow-up data analysis for CLIP-seq, both to refine the exact locations of RBP binding sites, and to characterize them. The specific properties of RBP binding sites, and the CLIP-seq methods, provide additional information not usually present in the classic motif discovery problem: the binding site structure, and cross-linking induced events in reads. We show that CLIP-seq data contains clear secondary structure signals, as well as technology- and RBP-specific cross-link signals. We introduce Zagros, a motif discovery algorithm specifically designed to leverage this information and explore its impact on the quality of recovered motifs. Our results indicate that using both secondary structure and cross-link modifications can greatly improve motif discovery on CLIP-seq data. Further, the motifs we recover provide insight into the balance between sequence- and structure-specificity struck by RBP binding.

  5. Directed Network Motifs in Alzheimer’s Disease and Mild Cognitive Impairment

    PubMed Central

    Friedman, Eric J.; Young, Karl; Tremper, Graham; Liang, Jason; Landsberg, Adam S.; Schuff, Norbert

    2015-01-01

    Directed network motifs are the building blocks of complex networks, such as human brain networks, and capture deep connectivity information that is not contained in standard network measures. In this paper we present the first application of directed network motifs in vivo to human brain networks, utilizing recently developed directed progression networks which are built upon rates of cortical thickness changes between brain regions. This is in contrast to previous studies which have relied on simulations and in vitro analysis of non-human brains. We show that frequencies of specific directed network motifs can be used to distinguish between patients with Alzheimer’s disease (AD) and normal control (NC) subjects. Especially interesting from a clinical standpoint, these motif frequencies can also distinguish between subjects with mild cognitive impairment who remained stable over three years (MCI) and those who converted to AD (CONV). Furthermore, we find that the entropy of the distribution of directed network motifs increased from MCI to CONV to AD, implying that the distribution of pathology is more structured in MCI but becomes less so as it progresses to CONV and further to AD. Thus, directed network motifs frequencies and distributional properties provide new insights into the progression of Alzheimer’s disease as well as new imaging markers for distinguishing between normal controls, stable mild cognitive impairment, MCI converters and Alzheimer’s disease. PMID:25879535

  6. Binding of the Grb2 SH2 domain to phosphotyrosine motifs does not change the affinity of its SH3 domains for Sos proline-rich motifs.

    PubMed

    Cussac, D; Frech, M; Chardin, P

    1994-09-01

    Phosphotyrosine peptide binding to Grb2 induces tryptophan fluorescence changes in the Src homology 2 (SH2) domain. Affinities are in the nanomolar range, the Shc peptide having the highest affinity, followed by peptides mimicking Grb2 binding sites on EGF and HGF receptors, the putative sites on insulin and IGF-1 receptors having much lower affinities. Proline-rich peptide binding to the SH3 domains induces fluorescence changes mainly in the C-terminal SH3. Affinities are in the micromolar range, the highest affinity peptides mimicking the first proline-rich motif of the Sos C-terminus. Additional residues before this PVPPPVPP motif provide a minor contribution to the binding, but the two residues after this motif are important and may contribute to specificity. The affinity of each SH3 for each proline-rich motif is too low to account for the high stability of the Grb2-Sos complex, suggesting that Grb2 recognizes other structural features in the Sos C-terminus. Binding of a phosphotyrosine peptide to the SH2 has no effect on the SH3s. Thus the binding of Grb2 to a receptor or to an associated protein phosphorylated on tyrosines is unlikely to activate the exchange factor activity of Sos through a conformational change transmitted from the SH2 to the SH3 domains.

  7. An Analysis of Multi-type Relational Interactions in FMA Using Graph Motifs with Disjointness Constraints

    SciTech Connect

    Zhang, Guo Qiang; Luo, Lingyun; Ogbuji, Chime; Joslyn, Cliff A.; Mejino, Jose; Sahoo, Satya S.

    2012-11-24

    The interaction of multiple types of relationships among anatomical classes in the Foundational Model of Anatomy (FMA) can provide inferred information valuable for quality assurance. This paper introduces a method called Motif Checking (MOCH) to study the effects of such multi-relation type interactions. MOCH represents patterns of multitype interaction as small labeled sub-graph motifs, whose nodes represent class variables, and labeled edges represent relational types. By representing FMA as an RDF graph and motifs as SPARQL queries, fragments of FMA are automatically obtained as auditing candidates. Leveraging the scalability and reconfigurability of Semantic Web Technology (OWL, RDF and SPARQL) and Virtuoso, we performed exhaustive analyses of three 2-node motifs, resulting in 638 matching FMA configurations; twelve 3-node motifs, resulting in 202,960 configurations. Using the Principal Ideal Explorer (PIE) methodology as an extension of MOCH, we were able to identify 755 root nodes with 4,100 respective descendants with opposing antonyms in their class names for arbitrary-length motifs. With possible disjointness implied by antonyms, we performed manual inspection of a subset of the resulting FMA fragments and tracked down a source of abnormal inferred conclusions (captured by the motifs), coming from a gender-neutral class being modeled as a part of gender-specific class, such as “Urinary system” is a part of “Female human body.” Our results demonstrate that MOCH and PIE provide a unique source of valuable information for quality assurance. Since our approach is general, it is applicable to any ontological system with an OWL representation.

  8. Helix-hairpin-helix motifs confer salt resistance and processivity on chimeric DNA polymerases.

    PubMed

    Pavlov, Andrey R; Belova, Galina I; Kozyavkin, Sergei A; Slesarev, Alexei I

    2002-10-15

    Helix-hairpin-helix (HhH) is a widespread motif involved in sequence-nonspecific DNA binding. The majority of HhH motifs function as DNA-binding modules with typical occurrence of one HhH motif or one or two (HhH)(2) domains in proteins. We recently identified 24 HhH motifs in DNA topoisomerase V (Topo V). Although these motifs are dispensable for the topoisomerase activity of Topo V, their removal narrows the salt concentration range for topoisomerase activity tenfold. Here, we demonstrate the utility of Topo V's HhH motifs for modulating DNA-binding properties of the Stoffel fragment of TaqDNA polymerase and Pfu DNA polymerase. Different HhH cassettes fused with either NH(2) terminus or COOH terminus of DNA polymerases broaden the salt concentration range of the polymerase activity significantly (up to 0.5 M NaCl or 1.8 M potassium glutamate). We found that anions play a major role in the inhibition of DNA polymerase activity. The resistance of initial extension rates and the processivity of chimeric polymerases to salts depend on the structure of added HhH motifs. Regardless of the type of the construct, the thermal stability of chimeric Taq polymerases increases under the optimal ionic conditions, as compared with that of TaqDNA polymerase or its Stoffel fragment. Our approach to raise the salt tolerance, processivity, and thermostability of Taq and Pfu DNA polymerases may be applied to all pol1- and polB-type polymerases, as well as to other DNA processing enzymes.

  9. Structural basis for the binding of tryptophan-based motifs by δ-COP

    PubMed Central

    Suckling, Richard J.; Poon, Pak Phi; Travis, Sophie M.; Majoul, Irina V.; Hughson, Frederick M.; Evans, Philip R.; Duden, Rainer; Owen, David J.

    2015-01-01

    Coatomer consists of two subcomplexes: the membrane-targeting, ADP ribosylation factor 1 (Arf1):GTP-binding βγδζ-COP F-subcomplex, which is related to the adaptor protein (AP) clathrin adaptors, and the cargo-binding αβ’ε-COP B-subcomplex. We present the structure of the C-terminal μ-homology domain of the yeast δ-COP subunit in complex with the WxW motif from its binding partner, the endoplasmic reticulum-localized Dsl1 tether. The motif binds at a site distinct from that used by the homologous AP μ subunits to bind YxxΦ cargo motifs with its two tryptophan residues sitting in compatible pockets. We also show that the Saccharomyces cerevisiae Arf GTPase-activating protein (GAP) homolog Gcs1p uses a related WxxF motif at its extreme C terminus to bind to δ-COP at the same site in the same way. Mutations designed on the basis of the structure in conjunction with isothermal titration calorimetry confirm the mode of binding and show that mammalian δ-COP binds related tryptophan-based motifs such as that from ArfGAP1 in a similar manner. We conclude that δ-COP subunits bind Wxn(1–6)[WF] motifs within unstructured regions of proteins that influence the lifecycle of COPI-coated vesicles; this conclusion is supported by the observation that, in the context of a sensitizing domain deletion in Dsl1p, mutating the tryptophan-based motif-binding site in yeast causes defects in both growth and carboxypeptidase Y trafficking/processing. PMID:26578768

  10. Subtle Changes in Motif Positioning Cause Tissue-Specific Effects on Robustness of an Enhancer's Activity

    PubMed Central

    Erceg, Jelena; Saunders, Timothy E.; Girardot, Charles; Devos, Damien P.; Hufnagel, Lars; Furlong, Eileen E. M.

    2014-01-01

    Deciphering the specific contribution of individual motifs within cis-regulatory modules (CRMs) is crucial to understanding how gene expression is regulated and how this process is affected by sequence variation. But despite vast improvements in the ability to identify where transcription factors (TFs) bind throughout the genome, we are limited in our ability to relate information on motif occupancy to function from sequence alone. Here, we engineered 63 synthetic CRMs to systematically assess the relationship between variation in the content and spacing of motifs within CRMs to CRM activity during development using Drosophila transgenic embryos. In over half the cases, very simple elements containing only one or two types of TF binding motifs were capable of driving specific spatio-temporal patterns during development. Different motif organizations provide different degrees of robustness to enhancer activity, ranging from binary on-off responses to more subtle effects including embryo-to-embryo and within-embryo variation. By quantifying the effects of subtle changes in motif organization, we were able to model biophysical rules that explain CRM behavior and may contribute to the spatial positioning of CRM activity in vivo. For the same enhancer, the effects of small differences in motif positions varied in developmentally related tissues, suggesting that gene expression may be more susceptible to sequence variation in one tissue compared to another. This result has important implications for human eQTL studies in which many associated mutations are found in cis-regulatory regions, though the mechanism for how they affect tissue-specific gene expression is often not understood. PMID:24391522

  11. Structural basis for the binding of tryptophan-based motifs by δ-COP.

    PubMed

    Suckling, Richard J; Poon, Pak Phi; Travis, Sophie M; Majoul, Irina V; Hughson, Frederick M; Evans, Philip R; Duden, Rainer; Owen, David J

    2015-11-17

    Coatomer consists of two subcomplexes: the membrane-targeting, ADP ribosylation factor 1 (Arf1):GTP-binding βγδζ-COP F-subcomplex, which is related to the adaptor protein (AP) clathrin adaptors, and the cargo-binding αβ'ε-COP B-subcomplex. We present the structure of the C-terminal μ-homology domain of the yeast δ-COP subunit in complex with the WxW motif from its binding partner, the endoplasmic reticulum-localized Dsl1 tether. The motif binds at a site distinct from that used by the homologous AP μ subunits to bind YxxΦ cargo motifs with its two tryptophan residues sitting in compatible pockets. We also show that the Saccharomyces cerevisiae Arf GTPase-activating protein (GAP) homolog Gcs1p uses a related WxxF motif at its extreme C terminus to bind to δ-COP at the same site in the same way. Mutations designed on the basis of the structure in conjunction with isothermal titration calorimetry confirm the mode of binding and show that mammalian δ-COP binds related tryptophan-based motifs such as that from ArfGAP1 in a similar manner. We conclude that δ-COP subunits bind Wxn(1-6)[WF] motifs within unstructured regions of proteins that influence the lifecycle of COPI-coated vesicles; this conclusion is supported by the observation that, in the context of a sensitizing domain deletion in Dsl1p, mutating the tryptophan-based motif-binding site in yeast causes defects in both growth and carboxypeptidase Y trafficking/processing.

  12. The Frequency of Internal Shine-Dalgarno-like Motifs in Prokaryotes.

    PubMed

    Diwan, Gaurav D; Agashe, Deepa

    2016-06-14

    In prokaryotes, translation initiation typically depends on complementary binding between a G-rich Shine-Dalgarno (SD) motif in the 5' untranslated region of mRNAs, and the 3' tail of the 16S ribosomal RNA (the anti-SD sequence). In some cases, internal SD-like motifs in the coding region generate "programmed" ribosomal pauses that are beneficial for protein folding or accurate targeting. On the other hand, such pauses can also reduce protein production, generating purifying selection against internal SD-like motifs. This selection should be stronger in GC-rich genomes that are more likely to harbor the G-rich SD motif. However, the nature and consequences of selection acting on internal SD-like motifs within genomes and across species remains unclear. We analyzed the frequency of SD-like hexamers in the coding regions of 284 prokaryotes (277 with known anti-SD sequences and 7 without a typical SD mechanism). After accounting for GC content, we found that internal SD-like hexamers are avoided in 230 species, including three without a typical SD mechanism. The degree of avoidance was higher in GC-rich genomes, mesophiles, and N-terminal regions of genes. In contrast, 54 species either showed no signature of avoidance or were enriched in internal SD-like motifs. C-terminal gene regions were relatively enriched in SD-like hexamers, particularly for genes in operons or those followed closely by downstream genes. Together, our results suggest that the frequency of internal SD-like hexamers is governed by multiple factors including GC content and genome organization, and further empirical work is necessary to understand the evolution and functional roles of these motifs.

  13. Molecular diversity of LysM carbohydrate-binding motifs in fungi.

    PubMed

    Akcapinar, Gunseli Bayram; Kappel, Lisa; Sezerman, Osman Ugur; Seidl-Seiboth, Verena

    2015-05-01

    LysM motifs are carbohydrate-binding modules found in prokaryotes and eukaryotes. They bind to N-acetylglucosamine-containing carbohydrates, such as chitin, chitio-oligosaccharides and peptidoglycan. In this review, we summarize the features of the protein architecture of LysM-containing proteins in fungi and discuss their so far known biochemical properties, transcriptional profiles and biological functions. Further, based on data from evolutionary analyses and consensus pattern profiling of fungal LysM motifs, we show that they can be classified into a fungal-specific group and a fungal/bacterial group. This facilitates the classification and selection of further LysM proteins for detailed analyses and will contribute to widening our understanding of the functional spectrum of this protein family in fungi. Fungal LysM motifs are predominantly found in subgroup C chitinases and in LysM effector proteins, which are secreted proteins with LysM motifs but no catalytic domains. In enzymes, LysM motifs mediate the attachment to insoluble carbon sources. In plants, receptors containing LysM motifs are responsible for the perception of chitin-oligosaccharides and are involved in beneficial symbiotic interactions between plants and bacteria or fungi, as well as plant defence responses. In plant pathogenic fungi, LysM effector proteins have already been shown to have important functions in the dampening of host defence responses as well as protective functions of fungal hyphae against chitinases. However, the large number and diversity of proteins with LysM motifs that are being unravelled in fungal genome sequencing projects suggest that the functional repertoire of LysM effector proteins in fungi is only partially discovered so far.

  14. Superatoms and Metal-Semiconductor Motifs for Cluster Materials

    SciTech Connect

    Castleman, A. W.

    2013-10-11

    A molecular understanding of catalysis and catalytically active materials is of fundamental importance in designing new substances for applications in energy and fuels. We have performed reactivity studies and ultrafast ionization and coulomb explosion studies on a variety of catalytically-relevant materials, including transition metal oxides of Fe, Co, Ni, Cu, Ti, V, Nb, and Ta. We demonstrate that differences in charge state, geometry, and elemental composition of clusters of such materials determine chemical reactivity and ionization behavior, crucial steps in improving performance of catalysts.

  15. Disparate requirements for the Walker A and B ATPase motifs ofhuman RAD51D in homologous recombination

    SciTech Connect

    Wiese, Claudia; Hinz, John M.; Tebbs, Robert S.; Nham, Peter B.; Urbin, Salustra S.; Collins, David W.; Thompson, Larry H.; Schild, David

    2006-04-21

    In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C, and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks. Ectopic expression of wild type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments using the yeast two- and three-hybrid systems show that the interactions between RAD51D and its XRCC2 and RAD51C partners also require a functional RAD51D B motif, but not motif A. Similarly, hamster Xrcc2 is unable to bind to the non-complementing human RAD51D B-motif mutants in co-immunoprecipitation assays. We conclude that a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR. We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs.

  16. CDR3 clonotype and amino acid motif diversity of BV19 expressing circulating human CD8 T cells

    PubMed Central

    Yassai, Maryam B.; Demos, Wendy; Janczak, Teresa; Naumova, Elena N.; Gorski, Jack

    2015-01-01

    Generating a detailed description of human T cell repertoire diversity is an important goal in the study of human immunology. The circulation is the source of most T cells used for studies in humans. Here we use high throughput sequencing of TCR BV19 transcripts from CD8 T cells derived from unmanipulated PBMC from an older HLA-A2 individual to provide a quantitative and qualitative description of the clonotypic CDR3 nucleotide and amino acid composition of the TCR β-chain from this subset of circulating CD8 T cells. Aggregated samples from six time points spanning ~ 1.5 years were analyzed to smooth possible temporal fluctuation. BV19 encompasses the well studied RS-encoding clonotypes involved in recognition of the M158–66 epitope from influenza A in HLA-A2 individuals. The clonotype distribution was diverse, complex and self-similar. The amino acid composition was generally skewed in favor of glycines and there were specific amino acids observed at higher frequency at the NDN start position. The motif repertoire distribution was also diverse, complex and self-similar with respect to CDR3 length, NDN start and length. PMID:26593155

  17. A double mutant knockin of the CD28 YMNM and PYAP motifs reveals a critical role for the YMNM motif in regulation of T cell proliferation and Bcl-Xl expression1

    PubMed Central

    Boomer, Jonathan S.; Deppong, Christine M.; Shah, Dulari D.; Bricker, Traci L.; Green, Jonathan M.

    2014-01-01

    CD28 is a critical regulator of T cell function, augmenting proliferation, cytokine secretion and cell survival. Our previous work using knockin mice expressing point mutations in CD28 had demonstrated that the distal proline motif was primarily responsible for much of CD28 function, whereas in marked contrast to prior studies, mutation of the PI3-kinase binding motif had little discernible effect. In this study, we examined the phenotype of mice in which both motifs are simultaneously mutated. We found that mutation of the PYAP motif unmasks a critical role for the proximal tyrosine motif in regulating T cell proliferation and expression of Bcl-Xl, but not cytokine secretion. In addition, we demonstrated that while function is more severely impaired in the double mutant than in either single mutant, there remained residual CD28-dependent responses, definitively establishing that additional motifs can partially mediate CD28 function. PMID:24639356

  18. Different electrostatic potentials define ETGE and DLG motifs as hinge and latch in oxidative stress response.

    PubMed

    Tong, Kit I; Padmanabhan, Balasundaram; Kobayashi, Akira; Shang, Chengwei; Hirotsu, Yosuke; Yokoyama, Shigeyuki; Yamamoto, Masayuki

    2007-11-01

    Nrf2 is the regulator of the oxidative/electrophilic stress response. Its turnover is maintained by Keap1-mediated proteasomal degradation via a two-site substrate recognition mechanism in which two Nrf2-Keap1 binding sites form a hinge and latch. The E3 ligase adaptor Keap1 recognizes Nrf2 through its conserved ETGE and DLG motifs. In this study, we examined how the ETGE and DLG motifs bind to Keap1 in a very similar fashion but with different binding affinities by comparing the crystal complex of a Keap1-DC domain-DLG peptide with that of a Keap1-DC domain-ETGE peptide. We found that these two motifs interact with the same basic surface of either Keap1-DC domain of the Keap1 homodimer. The DLG motif works to correctly position the lysines within the Nrf2 Neh2 domain for efficient ubiquitination. Together with the results from calorimetric and functional studies, we conclude that different electrostatic potentials primarily define the ETGE and DLG motifs as a hinge and latch that senses the oxidative/electrophilic stress.

  19. Effects of rate-limiting steps in transcription initiation on genetic filter motifs.

    PubMed

    Häkkinen, Antti; Tran, Huy; Yli-Harja, Olli; Ribeiro, Andre S

    2013-01-01

    The behavior of genetic motifs is determined not only by the gene-gene interactions, but also by the expression patterns of the constituent genes. Live single-molecule measurements have provided evidence that transcription initiation is a sequential process, whose kinetics plays a key role in the dynamics of mRNA and protein numbers. The extent to which it affects the behavior of cellular motifs is unknown. Here, we examine how the kinetics of transcription initiation affects the behavior of motifs performing filtering in amplitude and frequency domain. We find that the performance of each filter is degraded as transcript levels are lowered. This effect can be reduced by having a transcription process with more steps. In addition, we show that the kinetics of the stepwise transcription initiation process affects features such as filter cutoffs. These results constitute an assessment of the range of behaviors of genetic motifs as a function of the kinetics of transcription initiation, and thus will aid in tuning of synthetic motifs to attain specific characteristics without affecting their protein products.

  20. Defining and searching for structural motifs using DeepView/Swiss-PdbViewer

    PubMed Central

    2012-01-01

    Background Today, recognition and classification of sequence motifs and protein folds is a mature field, thanks to the availability of numerous comprehensive and easy to use software packages and web-based services. Recognition of structural motifs, by comparison, is less well developed and much less frequently used, possibly due to a lack of easily accessible and easy to use software. Results In this paper, we describe an extension of DeepView/Swiss-PdbViewer through which structural motifs may be defined and searched for in large protein structure databases, and we show that common structural motifs involved in stabilizing protein folds are present in evolutionarily and structurally unrelated proteins, also in deeply buried locations which are not obviously related to protein function. Conclusions The possibility to define custom motifs and search for their occurrence in other proteins permits the identification of recurrent arrangements of residues that could have structural implications. The possibility to do so without having to maintain a complex software/hardware installation on site brings this technology to experts and non-experts alike. PMID:22823337

  1. Designing synthetic RNAs to determine the relevance of structural motifs in picornavirus IRES elements

    NASA Astrophysics Data System (ADS)

    Fernandez-Chamorro, Javier; Lozano, Gloria; Garcia-Martin, Juan Antonio; Ramajo, Jorge; Dotu, Ivan; Clote, Peter; Martinez-Salas, Encarnacion

    2016-04-01

    The function of Internal Ribosome Entry Site (IRES) elements is intimately linked to their RNA structure. Viral IRES elements are organized in modular domains consisting of one or more stem-loops that harbor conserved RNA motifs critical for internal initiation of translation. A conserved motif is the pyrimidine-tract located upstream of the functional initiation codon in type I and II picornavirus IRES. By computationally designing synthetic RNAs to fold into a structure that sequesters the polypyrimidine tract in a hairpin, we establish a correlation between predicted inaccessibility of the pyrimidine tract and IRES activity, as determined in both in vitro and in vivo systems. Our data supports the hypothesis that structural sequestration of the pyrimidine-tract within a stable hairpin inactivates IRES activity, since the stronger the stability of the hairpin the higher the inhibition of protein synthesis. Destabilization of the stem-loop immediately upstream of the pyrimidine-tract also decreases IRES activity. Our work introduces a hybrid computational/experimental method to determine the importance of structural motifs for biological function. Specifically, we show the feasibility of using the software RNAiFold to design synthetic RNAs with particular sequence and structural motifs that permit subsequent experimental determination of the importance of such motifs for biological function.

  2. The position of the Gly-xxx-Gly motif in transmembrane segments modulates dimer affinity.

    PubMed

    Johnson, Rachel M; Rath, Arianna; Deber, Charles M

    2006-12-01

    Although the intrinsic low solubility of membrane proteins presents challenges to their high-resolution structure determination, insight into the amino acid sequence features and forces that stabilize their folds has been provided through study of sequence-dependent helix-helix interactions between single transmembrane (TM) helices. While the stability of helix-helix partnerships mediated by the Gly-xxx-Gly (GG4) motif is known to be generally modulated by distal interfacial residues, it has not been established whether the position of this motif, with respect to the ends of a given TM segment, affects dimer affinity. Here we examine the relationship between motif position and affinity in the homodimers of 2 single-spanning membrane protein TM sequences: glycophorin A (GpA) and bacteriophage M13 coat protein (MCP). Using the TOXCAT assay for dimer affinity on a series of GpA and MCP TM segments that have been modified with either 4 Leu residues at each end or with 8 Leu residues at the N-terminal end, we show that in each protein, centrally located GG4 motifs are capable of stronger helix-helix interactions than those proximal to TM helix ends, even when surrounding interfacial residues are maintained. The relative importance of GG4 motifs in stabilizing helix-helix interactions therefore must be considered not only in its specific residue context but also in terms of the location of the interactive surface relative to the N and C termini of alpha-helical TM segments.

  3. A conserved motif mediates both multimer formation and allosteric activation of phosphoglycerate mutase 5.

    PubMed

    Wilkins, Jordan M; McConnell, Cyrus; Tipton, Peter A; Hannink, Mark

    2014-09-05

    Phosphoglycerate mutase 5 (PGAM5) is an atypical mitochondrial Ser/Thr phosphatase that modulates mitochondrial dynamics and participates in both apoptotic and necrotic cell death. The mechanisms that regulate the phosphatase activity of PGAM5 are poorly understood. The C-terminal phosphoglycerate mutase domain of PGAM5 shares homology with the catalytic domains found in other members of the phosphoglycerate mutase family, including a conserved histidine that is absolutely required for catalytic activity. However, this conserved domain is not sufficient for maximal phosphatase activity. We have identified a highly conserved amino acid motif, WDXNWD, located within the unique N-terminal region, which is required for assembly of PGAM5 into large multimeric complexes. Alanine substitutions within the WDXNWD motif abolish the formation of multimeric complexes and markedly reduce phosphatase activity of PGAM5. A peptide containing the WDXNWD motif dissociates the multimeric complex and reduces but does not fully abolish phosphatase activity. Addition of the WDXNWD-containing peptide in trans to a mutant PGAM5 protein lacking the WDXNWD motif markedly increases phosphatase activity of the mutant protein. Our results are consistent with an intermolecular allosteric regulation mechanism for the phosphatase activity of PGAM5, in which the assembly of PGAM5 into multimeric complexes, mediated by the WDXNWD motif, results in maximal activation of phosphatase activity. Our results suggest the possibility of identifying small molecules that function as allosteric regulators of the phosphatase activity of PGAM5.

  4. Analysis of Co-Associated Transcription Factors via Ordered Adjacency Differences on Motif Distribution

    PubMed Central

    Pan, Gaofeng; Tang, Jijun; Guo, Fei

    2017-01-01

    Transcription factors (TFs) binding to specific DNA sequences or motifs, are elementary to the regulation of transcription. The gene is regulated by a combination of TFs in close proximity. Analysis of co-TFs is an important problem in understanding the mechanism of transcriptional regulation. Recently, ChIP-seq in mapping TF provides a large amount of experimental data to analyze co-TFs. Several studies show that if two TFs are co-associated, the relative distance between TFs exhibits a peak-like distribution. In order to analyze co-TFs, we develop a novel method to evaluate the associated situation between TFs. We design an adjacency score based on ordered differences, which can illustrate co-TF binding affinities for motif analysis. For all candidate motifs, we calculate corresponding adjacency scores, and then list descending-order motifs. From these lists, we can find co-TFs for candidate motifs. On ChIP-seq datasets, our method obtains best AUC results on five datasets, 0.9432 for NMYC, 0.9109 for KLF4, 0.9006 for ZFX, 0.8892 for ESRRB, 0.8920 for E2F1. Our method has great stability on large sample datasets. AUC results of our method on all datasets are above 0.8. PMID:28240320

  5. RNA tertiary interactions in the large ribosomal subunit: The A-minor motif

    SciTech Connect

    Nissen, Poul; Ippolito, Joseph A.; Ban, Nenad; Moore, Peter B.; Steitz, Thomas A.

    2009-10-07

    Analysis of the 2.4-{angstrom} resolution crystal structure of the large ribosomal subunit from Haloarcula marismortui reveals the existence of an abundant and ubiquitous structural motif that stabilizes RNA tertiary and quaternary structures. This motif is termed the A-minor motif, because it involves the insertion of the smooth, minor groove edges of adenines into the minor groove of neighboring helices, preferentially at C-G base pairs, where they form hydrogen bonds with one or both of the 2' OHs of those pairs. A-minor motifs stabilize contacts between RNA helices, interactions between loops and helices, and the conformations of junctions and tight turns. The interactions between the 3' terminal adenine of tRNAs bound in either the A site or the P site with 23S rRNA are examples of functionally significant A-minor interactions. The A-minor motif is by far the most abundant tertiary structure interaction in the large ribosomal subunit; 186 adenines in 23S and 5S rRNA participate, 68 of which are conserved. It may prove to be the universally most important long-range interaction in large RNA structures.

  6. Olf-1-binding site: characterization of an olfactory neuron-specific promoter motif.

    PubMed Central

    Kudrycki, K; Stein-Izsak, C; Behn, C; Grillo, M; Akeson, R; Margolis, F L

    1993-01-01

    We report characterization of several domains within the 5' flanking region of the olfactory marker protein (OMP) gene that may participate in regulating transcription of this and other olfactory neuron-specific genes. Analysis by electrophoretic mobility shift assay and DNase I footprinting identifies two regions that contain a novel sequence motif. Interactions between this motif and nuclear proteins were detected only with nuclear protein extracts derived from olfactory neuroepithelium, and this activity is more abundant in olfactory epithelium enriched in immature neurons. We have designated a factor(s) involved in this binding as Olf-1. The Olf-1-binding motif consensus sequence was defined as TCCCC(A/T)NGGAG. Studies with transgenic mice indicate that a 0.3-kb fragment of the OMP gene containing one Olf-1 motif is sufficient for olfactory tissue-specific expression of the reporter gene. Some of the other identified sequence motifs also interact specifically with olfactory nuclear protein extracts. We propose that Olf-1 is a novel, olfactory neuron-specific trans-acting factor involved in the cell-specific expression of OMP. Images PMID:8474458

  7. Distribution of hammerhead and hammerhead-like RNA motifs through the GenBank.

    PubMed

    Ferbeyre, G; Bourdeau, V; Pageau, M; Miramontes, P; Cedergren, R

    2000-07-01

    Hammerhead ribozymes previously were found in satellite RNAs from plant viroids and in repetitive DNA from certain species of newts and schistosomes. To determine if this catalytic RNA motif has a wider distribution, we decided to scrutinize the GenBank database for RNAs that contain hammerhead or hammerhead-like motifs. The search shows a widespread distribution of this kind of RNA motif in different sequences suggesting that they might have a more general role in RNA biology. The frequency of the hammerhead motif is half of that expected from a random distribution, but this fact comes from the low CpG representation in vertebrate sequences and the bias of the GenBank for those sequences. Intriguing motifs include those found in several families of repetitive sequences, in the satellite RNA from the carrot red leaf luteovirus, in plant viruses like the spinach latent virus and the elm mottle virus, in animal viruses like the hepatitis E virus and the caprine encephalitis virus, and in mRNAs such as those coding for cytochrome P450 oxidoreductase in the rat and the hamster.

  8. A novel secondary structure based on fused five-membered rings motif

    PubMed Central

    Dhar, Jesmita; Kishore, Raghuvansh; Chakrabarti, Pinak

    2016-01-01

    An analysis of protein structures indicates the existence of a novel, fused five-membered rings motif, comprising of two residues (i and i + 1), stabilized by interresidue Ni+1–H∙∙∙Ni and intraresidue Ni+1–H∙∙∙O=Ci+1 hydrogen bonds. Fused-rings geometry is the common thread running through many commonly occurring motifs, such as β-turn, β-bulge, Asx-turn, Ser/Thr-turn, Schellman motif, and points to its structural robustness. A location close to the beginning of a β-strand is rather common for the motif. Devoid of side chain, Gly seems to be a key player in this motif, occurring at i, for which the backbone torsion angles cluster at ~(−90°, −10°) and (70°, 20°). The fused-rings structures, distant from each other in sequence, can hydrogen bond with each other, and the two segments aligned to each other in a parallel fashion, give rise to a novel secondary structure, topi, which is quite common in proteins, distinct from two major secondary structures, α-helix and β-sheet. Majority of the peptide segments making topi are identified as aggregation-prone and the residues tend to be conserved among homologous proteins. PMID:27511362

  9. Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure.

    PubMed Central

    Thayer, M M; Ahern, H; Xing, D; Cunningham, R P; Tainer, J A

    1995-01-01

    The 1.85 A crystal structure of endonuclease III, combined with mutational analysis, suggests the structural basis for the DNA binding and catalytic activity of the enzyme. Helix-hairpin-helix (HhH) and [4Fe-4S] cluster loop (FCL) motifs, which we have named for their secondary structure, bracket the cleft separating the two alpha-helical domains of the enzyme. These two novel DNA binding motifs and the solvent-filled pocket in the cleft between them all lie within a positively charged and sequence-conserved surface region. Lys120 and Asp138, both shown by mutagenesis to be catalytically important, lie at the mouth of this pocket, suggesting that this pocket is part of the active site. The positions of the HhH motif and protruding FCL motif, which contains the DNA binding residue Lys191, can accommodate B-form DNA, with a flipped-out base bound within the active site pocket. The identification of HhH and FCL sequence patterns in other DNA binding proteins suggests that these motifs may be a recurrent structural theme for DNA binding proteins. Images PMID:7664751

  10. Alanine substitutions of noncysteine residues in the cysteine-stabilized αβ motif

    PubMed Central

    Yang, Ying-Fang; Cheng, Kuo-Chang; Tsai, Ping-Hsing; Liu, Chung-Cheng; Lee, Tian-Ren; Ping-Chiang Lyu

    2009-01-01

    The protein scaffold is a peptide framework with a high tolerance of residue modifications. The cysteine-stabilized αβ motif (CSαβ) consists of an α-helix and an antiparallel triple-stranded β-sheet connected by two disulfide bridges. Proteins containing this motif share low sequence identity but high structural similarity and has been suggested as a good scaffold for protein engineering. The Vigna radiate defensin 1 (VrD1), a plant defensin, serves here as a model protein to probe the amino acid tolerance of CSαβ motif. A systematic alanine substitution is performed on the VrD1. The key residues governing the inhibitory function and structure stability are monitored. Thirty-two of 46 residue positions of VrD1 are altered by site-directed mutagenesis techniques. The circular dichroism spectrum, intrinsic fluorescence spectrum, and chemical denaturation are used to analyze the conformation and structural stability of proteins. The secondary structures were highly tolerant to the amino acid substitutions; however, the protein stabilities were varied for each mutant. Many mutants, although they maintained their conformations, altered their inhibitory function significantly. In this study, we reported the first alanine scan on the plant defensin containing the CSαβ motif. The information is valuable to the scaffold with the CSαβ motif and protein engineering. PMID:19533758

  11. qPMS9: An Efficient Algorithm for Quorum Planted Motif Search

    NASA Astrophysics Data System (ADS)

    Nicolae, Marius; Rajasekaran, Sanguthevar

    2015-01-01

    Discovering patterns in biological sequences is a crucial problem. For example, the identification of patterns in DNA sequences has resulted in the determination of open reading frames, identification of gene promoter elements, intron/exon splicing sites, and SH RNAs, location of RNA degradation signals, identification of alternative splicing sites, etc. In protein sequences, patterns have led to domain identification, location of protease cleavage sites, identification of signal peptides, protein interactions, determination of protein degradation elements, identification of protein trafficking elements, discovery of short functional motifs, etc. In this paper we focus on the identification of an important class of patterns, namely, motifs. We study the (l, d) motif search problem or Planted Motif Search (PMS). PMS receives as input n strings and two integers l and d. It returns all sequences M of length l that occur in each input string, where each occurrence differs from M in at most d positions. Another formulation is quorum PMS (qPMS), where the motif appears in at least q% of the strings. We introduce qPMS9, a parallel exact qPMS algorithm that offers significant runtime improvements on DNA and protein datasets. qPMS9 solves the challenging DNA (l, d)-instances (28, 12) and (30, 13). The source code is available at https://code.google.com/p/qpms9/.

  12. DNA motifs determining the efficiency of adaptation into the Escherichia coli CRISPR array.

    PubMed

    Yosef, Ido; Shitrit, Dror; Goren, Moran G; Burstein, David; Pupko, Tal; Qimron, Udi

    2013-08-27

    Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins constitute a recently identified prokaryotic defense system against invading nucleic acids. DNA segments, termed protospacers, are integrated into the CRISPR array in a process called adaptation. Here, we establish a PCR-based assay that enables evaluating the adaptation efficiency of specific spacers into the type I-E Escherichia coli CRISPR array. Using this assay, we provide direct evidence that the protospacer adjacent motif along with the first base of the protospacer (5'-AAG) partially affect the efficiency of spacer acquisition. Remarkably, we identified a unique dinucleotide, 5'-AA, positioned at the 3' end of the spacer, that enhances efficiency of the spacer's acquisition. Insertion of this dinucleotide increased acquisition efficiency of two different spacers. DNA sequencing of newly adapted CRISPR arrays revealed that the position of the newly identified motif with respect to the 5'-AAG is important for affecting acquisition efficiency. Analysis of approximately 1 million spacers showed that this motif is overrepresented in frequently acquired spacers compared with those acquired rarely. Our results represent an example of a short nonprotospacer adjacent motif sequence that affects acquisition efficiency and suggest that other as yet unknown motifs affect acquisition efficiency in other CRISPR systems as well.

  13. A Conserved Di-Basic Motif of Drosophila Crumbs Contributes to Efficient ER Export.

    PubMed

    Kumichel, Alexandra; Kapp, Katja; Knust, Elisabeth

    2015-06-01

    The Drosophila type I transmembrane protein Crumbs is an apical determinant required for the maintenance of apico-basal epithelial cell polarity. The level of Crumbs at the plasma membrane is crucial, but how it is regulated is poorly understood. In a genetic screen for regulators of Crumbs protein trafficking we identified Sar1, the core component of the coat protein complex II transport vesicles. sar1 mutant embryos show a reduced plasma membrane localization of Crumbs, a defect similar to that observed in haunted and ghost mutant embryos, which lack Sec23 and Sec24CD, respectively. By pulse-chase assays in Drosophila Schneider cells and analysis of protein transport kinetics based on Endoglycosidase H resistance we identified an RNKR motif in Crumbs, which contributes to efficient ER export. The motif identified fits the highly conserved di-basic RxKR motif and mediates interaction with Sar1. The RNKR motif is also required for plasma membrane delivery of transgene-encoded Crumbs in epithelial cells of Drosophila embryos. Our data are the first to show that a di-basic motif acts as a signal for ER exit of a type I plasma membrane protein in a metazoan organism.

  14. High affinity recognition of a Phytophthora protein by Arabidopsis via an RGD motif.

    PubMed

    Senchou, V; Weide, R; Carrasco, A; Bouyssou, H; Pont-Lezica, R; Govers, F; Canut, H

    2004-02-01

    The RGD tripeptide sequence, a cell adhesion motif present in several extracellular matrix proteins of mammalians, is involved in numerous plant processes. In plant-pathogen interactions, the RGD motif is believed to reduce plant defence responses by disrupting adhesions between the cell wall and plasma membrane. Photoaffinity cross-linking of [125I]-azido-RGD heptapeptide in the presence of purified plasma membrane vesicles of Arabidopsis thaliana led to label incorporation into a single protein with an apparent molecular mass of 80 kDa. Incorporation could be prevented by excess RGD peptides, but also by the IPI-O protein, an RGD-containing protein secreted by the oomycete plant pathogen Phytophthora infestans. Hydrophobic cluster analysis revealed that the RGD motif of IPI-O (positions 53-56) is readily accessible for interactions. Single amino acid mutations in the RGD motif in IPI-O (of Asp56 into Glu or Ala) resulted in the loss of protection of the 80-kDa protein from labelling. Thus, the interaction between the two proteins is mediated through RGD recognition and the 80-kDa RGD-binding protein has the characteristics of a receptor for IPI-O. The IPI-O protein also disrupted cell wall-plasma membrane adhesions in plasmolysed A. thaliana cells, whereas IPI-O proteins mutated in the RGD motif (D56A and D56E) did not.

  15. Cofunctional Subpathways Were Regulated by Transcription Factor with Common Motif, Common Family, or Common Tissue.

    PubMed

    Su, Fei; Shang, Desi; Xu, Yanjun; Feng, Li; Yang, Haixiu; Liu, Baoquan; Su, Shengyang; Chen, Lina; Li, Xia

    2015-01-01

    Dissecting the characteristics of the transcription factor (TF) regulatory subpathway is helpful for understanding the TF underlying regulatory function in complex biological systems. To gain insight into the influence of TFs on their regulatory subpathways, we constructed a global TF-subpathways network (TSN) to analyze systematically the regulatory effect of common-motif, common-family, or common-tissue TFs on subpathways. We performed cluster analysis to show that the common-motif, common-family, or common-tissue TFs that regulated the same pathway classes tended to cluster together and contribute to the same biological function that led to disease initiation and progression. We analyzed the Jaccard coefficient to show that the functional consistency of subpathways regulated by the TF pairs with common motif, common family, or common tissue was significantly greater than the random TF pairs at the subpathway level, pathway level, and pathway class level. For example, HNF4A (hepatocyte nuclear factor 4, alpha) and NR1I3 (nuclear receptor subfamily 1, group I, member 3) were a pair of TFs with common motif, common family, and common tissue. They were involved in drug metabolism pathways and were liver-specific factors required for physiological transcription. In short, we inferred that the cofunctional subpathways were regulated by common-motif, common-family, or common-tissue TFs.

  16. Composition-dependent stability of the medium-range order responsible for metallic glass formation

    SciTech Connect

    Zhang, Feng; Ji, Min; Fang, Xiao-Wei; Sun, Yang; Wang, Cai-Zhuang; Mendelev, Mikhail I.; Kramer, M. J.; Napolitano, Ralph E.; Ho, Kai-Ming

    2014-09-18

    The competition between the characteristic medium-range order corresponding to amorphous alloys and that in ordered crystalline phases is central to phase selection and morphology evolution under various processing conditions. We examine the stability of a model glass system, Cu–Zr, by comparing the energetics of various medium-range structural motifs over a wide range of compositions using first-principles calculations. Furthermore, we focus specifically on motifs that represent possible building blocks for competing glassy and crystalline phases, and we employ a genetic algorithm to efficiently identify the energetically favored decorations of each motif for specific compositions. These results show that a Bergman-type motif with crystallization-resisting icosahedral symmetry is energetically most favorable in the composition range 0.63 < xCu < 0.68, and is the underlying motif for one of the three optimal glass-forming ranges observed experimentally for this binary system (Li et al., 2008). This work establishes an energy-based methodology to evaluate specific medium-range structural motifs which compete with stable crystalline nuclei in deeply undercooled liquids.

  17. Local motifs involved in the canonical structure of the ligand-binding domain in the nuclear receptor superfamily.

    PubMed

    Tsuji, Motonori

    2014-03-01

    Structural and sequence alignment analyses have revealed the existence of class-dependent and -independent local motifs involved in the overall fold of the ligand-binding domain (LBD) in the nuclear receptor (NR) superfamily. Of these local motifs, three local motifs, i.e., AF-2 fixed motifs, were involved in the agonist conformation of the activation function-2 (AF-2) region of the LBD. Receptor-agonist interactions increased the stability of these AF-2 fixed motifs in the agonist conformation. In contrast, perturbation of the AF-2 fixed motifs by a ligand or another protein molecule led the AF-2 architecture to adopt an antagonist conformation. Knowledge of this process should provide us with novel insights into the 'agonism' and 'antagonism' of NRs.

  18. A dictionary of behavioral motifs reveals clusters of genes affecting C. elegans locomotion

    NASA Astrophysics Data System (ADS)

    Brown, Andre; Yemini, Eviatar; Grundy, Laura; Jucikas, Tadas; Schafer, William

    2013-03-01

    Visible phenotypes based on locomotion and posture have played a critical role in understanding the molecular basis of behavior and development in C. elegans and other model organisms. However, it is not known whether these human-defined features capture the most important aspects of behavior for phenotypic comparison nor whether they are sufficient to discover new behaviors. Here we show that four basic shapes, or eigenworms, previously described for wild type worms also capture mutant shapes, and that this representation can be used to build a dictionary of repetitive behavioral motifs in an unbiased way. By measuring the distance between each individual's behavior and the elements in the motif dictionary, we create a fingerprint that can be used to compare mutants to wild type and to each other. This analysis has revealed previously undescribed phenotypes and has allowed clustering of mutants into related groups. Behavioral motifs provide a compact and intuitive representation of behavioral phenotypes.

  19. Functional domains and motifs of bacterial type III effector proteins and their roles in infection.

    PubMed

    Dean, Paul

    2011-11-01

    A key feature of the virulence of many bacterial pathogens is the ability to deliver effector proteins into eukaryotic cells via a dedicated type three secretion system (T3SS). Many bacterial pathogens, including species of Chlamydia, Xanthomonas, Pseudomonas, Ralstonia, Shigella, Salmonella, Escherichia and Yersinia, depend on the T3SS to cause disease. T3SS effectors constitute a large and diverse group of virulence proteins that mimic eukaryotic proteins in structure and function. A salient feature of bacterial effectors is their modular architecture, comprising domains or motifs that confer an array of subversive functions within the eukaryotic cell. These domains/motifs therefore represent a fascinating repertoire of molecular determinants with important roles during infection. This review provides a snapshot of our current understanding of bacterial effector domains and motifs where a defined role in infection has been demonstrated.

  20. CPI motif interaction is necessary for capping protein function in cells

    PubMed Central

    Edwards, Marc; McConnell, Patrick; Schafer, Dorothy A.; Cooper, John A.

    2015-01-01

    Capping protein (CP) has critical roles in actin assembly in vivo and in vitro. CP binds with high affinity to the barbed end of actin filaments, blocking the addition and loss of actin subunits. Heretofore, models for actin assembly in cells generally assumed that CP is constitutively active, diffusing freely to find and cap barbed ends. However, CP can be regulated by binding of the ‘capping protein interaction' (CPI) motif, found in a diverse and otherwise unrelated set of proteins that decreases, but does not abolish, the actin-capping activity of CP and promotes uncapping in biochemical experiments. Here, we report that CP localization and the ability of CP to function in cells requires interaction with a CPI-motif-containing protein. Our discovery shows that cells target and/or modulate the capping activity of CP via CPI motif interactions in order for CP to localize and function in cells. PMID:26412145

  1. The VQ Motif-Containing Protein Family of Plant-Specific Transcriptional Regulators1

    PubMed Central

    Jing, Yanjun; Lin, Rongcheng

    2015-01-01

    The VQ motif-containing proteins (designated as VQ proteins) are a class of plant-specific proteins with a conserved and single short FxxhVQxhTG amino acid sequence motif. VQ proteins regulate diverse developmental processes, including responses to biotic and abiotic stresses, seed development, and photomorphogenesis. In this Update, we summarize and discuss recent advances in our understanding of the regulation and function of VQ proteins and the role of the VQ motif in mediating transcriptional regulation and protein-protein interactions in signaling pathways. Based on the accumulated evidence, we propose a general mechanism of action for the VQ protein family, which likely defines a novel class of transcriptional regulators specific to plants. PMID:26220951

  2. Definition of the consensus motif recognized by gamma-adaptin ear domains.

    PubMed

    Mattera, Rafael; Ritter, Brigitte; Sidhu, Sachdev S; McPherson, Peter S; Bonifacino, Juan S

    2004-02-27

    The heterotetrameric adaptor complex 1 (AP-1) and the monomeric Golgi-localized, gamma ear-containing, Arf-binding (GGA) proteins are components of clathrin coats associated with the trans-Golgi network and endosomes. The carboxyl-terminal ear domains (or gamma-adaptin ear (GAE) domains) of two gamma-adaptin subunit isoforms of AP-1 and of the GGAs are structurally similar and bind to a common set of accessory proteins. In this study, we have systematically defined a core tetrapeptide motif PsiG(P/D/E)(Psi/L/M) (where Psi is an aromatic residue), which is responsible for the interactions of accessory proteins with GAE domains. The definition of this motif has allowed us to identify novel GAE-binding partners named NECAP and aftiphilin, which also contain clathrin-binding motifs. These findings shed light on the mechanism of accessory protein recruitment to trans-Golgi network and endosomal clathrin coats.

  3. How motif environment influences transcription factor search dynamics: Finding a needle in a haystack

    PubMed Central

    Dror, Iris; Rohs, Remo

    2016-01-01

    Transcription factors (TFs) have to find their binding sites, which are distributed throughout the genome. Facilitated diffusion is currently the most widely accepted model for this search process. Based on this model the TF alternates between one‐dimensional sliding along the DNA, and three‐dimensional bulk diffusion. In this view, the non‐specific associations between the proteins and the DNA play a major role in the search dynamics. However, little is known about how the DNA properties around the motif contribute to the search. Accumulating evidence showing that TF binding sites are embedded within a unique environment, specific to each TF, leads to the hypothesis that the search process is facilitated by favorable DNA features that help to improve the search efficiency. Here, we review the field and present the hypothesis that TF‐DNA recognition is dictated not only by the motif, but is also influenced by the environment in which the motif resides. PMID:27192961

  4. Improved Exact Enumerative Algorithms for the Planted (l, d)-Motif Search Problem.

    PubMed

    Tanaka, Shunji

    2014-01-01

    In this paper efficient exact algorithms are proposed for the planted ( l, d)-motif search problem. This problem is to find all motifs of length l that are planted in each input string with at most d mismatches. The "quorum" version of this problem is also treated in this paper to find motifs planted not in all input strings but in at least q input strings. The proposed algorithms are based on the previous algorithms called qPMSPruneI and qPMS7 that traverse a search tree starting from a l-length substring of an input string. To improve these previous algorithms, several techniques are introduced, which contribute to reducing the computation time for the traversal. In computational experiments, it will be shown that the proposed algorithms outperform the previous algorithms.

  5. Viral immunoreceptor-associated tyrosine-based activation motifs: potential players in oncogenesis.

    PubMed

    Grande, Shannon M; Ross, Susan R; Monroe, John G

    2006-04-01

    Cancer is thought to arise as a consequence of multiple insults to a cell. Mutations that lead to increased expression or activity of proto-oncogenes or decreased expression of tumor suppressors are common insults that have been identified to date. However, when considering tumor viruses, viral proteins that modify cellular gene expression, alter host immune surveillance, or affect signaling pathways are also common players. Notably, several of these tumor viruses encode proteins containing an immunoreceptor-associated tyrosine-based activation motif (ITAM), a signaling motif recently implicated in epithelial cell oncogenesis. As expression of proteins bearing this motif is normally restricted to hematopoietic cells, recent work highlighting the consequences of ITAM expression in epithelial cells suggests it may play a role in solid tumor formation.

  6. Enteropathogenic Escherichia coli Tir recruits cellular SHP-2 through ITIM motifs to suppress host immune response.

    PubMed

    Yan, Dapeng; Quan, Heming; Wang, Lin; Liu, Feng; Liu, Haipeng; Chen, Jianxia; Cao, Xuetao; Ge, Baoxue

    2013-09-01

    Immune responses to pathogens are regulated by immune receptors containing either an immunoreceptor tyrosine-based activation motif (ITAM) or an immunoreceptor tyrosine-based inhibitory motif (ITIM). The important diarrheal pathogen enteropathogenic Escherichia coli (EPEC) require delivery and insertion of the bacterial translocated intimin receptor (Tir) into the host plasma membrane for pedestal formation. The C-terminal region of Tir, encompassing Y483 and Y511, shares sequence similarity with cellular ITIMs. Here, we show that EPEC Tir suppresses the production of inflammatory cytokines by recruitment of SHP-2 and subsequent deubiquitination of TRAF6 in an ITIM dependent manner. Our findings revealed a novel mechanism by which the EPEC utilize its ITIM motifs to suppress and evade the host innate immune response, which could lead to the development of novel therapeutics to prevent bacterial infection.

  7. Experimental Support for the Evolution of Symmetric Protein Architecture from a Simple Peptide Motif

    SciTech Connect

    J Lee; M Blaber

    2011-12-31

    The majority of protein architectures exhibit elements of structural symmetry, and 'gene duplication and fusion' is the evolutionary mechanism generally hypothesized to be responsible for their emergence from simple peptide motifs. Despite the central importance of the gene duplication and fusion hypothesis, experimental support for a plausible evolutionary pathway for a specific protein architecture has yet to be effectively demonstrated. To address this question, a unique 'top-down symmetric deconstruction' strategy was utilized to successfully identify a simple peptide motif capable of recapitulating, via gene duplication and fusion processes, a symmetric protein architecture (the threefold symmetric {beta}-trefoil fold). The folding properties of intermediary forms in this deconstruction agree precisely with a previously proposed 'conserved architecture' model for symmetric protein evolution. Furthermore, a route through foldable sequence-space between the simple peptide motif and extant protein fold is demonstrated. These results provide compelling experimental support for a plausible evolutionary pathway of symmetric protein architecture via gene duplication and fusion processes.

  8. Systematic and quantitative analysis of G protein-coupled receptor trafficking motifs.

    PubMed

    Hurt, Carl M; Ho, Vincent K; Angelotti, Timothy

    2013-01-01

    Plasma membrane expression of G protein-coupled receptors (GPCRs) is a dynamic process balancing anterograde and retrograde trafficking. Multiple interrelated cellular processes determine the final level of cell surface expression, including endoplasmic reticulum (ER) export/retention, receptor internalization, recycling, and degradation. These processes are highly regulated to achieve specific localization to subcellular domains (e.g., dendrites or basolateral membranes) and to affect receptor signaling. Analysis of potential ER trafficking motifs within GPCRs requires careful consideration of intracellular dynamics, such as protein folding, ER export and retention, and glycosylation. This chapter presents an approach and methods for qualitative and quantitative assessment of these processes to aid in accurate identification of GPCR trafficking motifs, utilizing the analysis of a hydrophobic extracellular trafficking motif in α2C adrenergic receptors as a model system.

  9. Mitogen-activated protein kinase 4-like carrying an MEY motif instead of a TXY motif is involved in ozone tolerance and regulation of stomatal closure in tobacco

    PubMed Central

    Yanagawa, Yuki; Yoda, Hiroshi; Osaki, Kohei; Amano, Yuta; Aono, Mitsuko; Seo, Shigemi; Kuchitsu, Kazuyuki; Mitsuhara, Ichiro

    2016-01-01

    The mitogen-activated protein kinases (MAPKs/MPKs) are important factors in the regulation of signal transduction in response to biotic and abiotic stresses. Previously, we characterized a MAPK from tobacco, Nicotiana tabacum MPK4 (NtMPK4). Here, we found a highly homologous gene, NtMPK4-like (NtMPK4L), in tobacco as well as other species in Solanaceae and Gramineae. Deduced amino acid sequences of their translation products carried MEY motifs instead of conserved TXY motifs of the MAPK family. We isolated the full length NtMPK4L gene and examined the physiological functions of NtMPK4L. We revealed that NtMPK4L was activated by wounding, like NtMPK4. However, a constitutively active salicylic acid-induced protein kinase kinase (SIPKKEE), which phosphorylates NtMPK4, did not phosphorylate NtMPK4L. Moreover, a tyrosine residue in the MEY motif was not involved in NtMPK4L activation. We also found that NtMPK4L-silenced plants showed rapid transpiration caused by remarkably open stomata. In addition, NtMPK4L-silenced plants completely lost the ability to close stomata upon ozone treatment and were highly sensitive to ozone, suggesting that this atypical MAPK plays a role in ozone tolerance through stomatal regulation. PMID:27126796

  10. Mutual enrichment in ranked lists and the statistical assessment of position weight matrix motifs

    PubMed Central

    2014-01-01

    Background Statistics in ranked lists is useful in analysing molecular biology measurement data, such as differential expression, resulting in ranked lists of genes, or ChIP-Seq, which yields ranked lists of genomic sequences. State of the art methods study fixed motifs in ranked lists of sequences. More flexible models such as position weight matrix (PWM) motifs are more challenging in this context, partially because it is not clear how to avoid the use of arbitrary thresholds. Results To assess the enrichment of a PWM motif in a ranked list we use a second ranking on the same set of elements induced by the PWM. Possible orders of one ranked list relative to another can be modelled as permutations. Due to sample space complexity, it is difficult to accurately characterize tail distributions in the group of permutations. In this paper we develop tight upper bounds on tail distributions of the size of the intersection of the top parts of two uniformly and independently drawn permutations. We further demonstrate advantages of this approach using our software implementation, mmHG-Finder, which is publicly available, to study PWM motifs in several datasets. In addition to validating known motifs, we found GC-rich strings to be enriched amongst the promoter sequences of long non-coding RNAs that are specifically expressed in thyroid and prostate tissue samples and observed a statistical association with tissue specific CpG hypo-methylation. Conclusions We develop tight bounds that can be calculated in polynomial time. We demonstrate utility of mutual enrichment in motif search and assess performance for synthetic and biological datasets. We suggest that thyroid and prostate-specific long non-coding RNAs are regulated by transcription factors that bind GC-rich sequences, such as EGR1, SP1 and E2F3. We further suggest that this regulation is associated with DNA hypo-methylation. PMID:24708618

  11. Electromagnetic Field Seems to Not Influence Transcription via CTCT Motif in Three Plant Promoters

    PubMed Central

    Sztafrowski, Dariusz; Aksamit-Stachurska, Anna; Kostyn, Kamil; Mackiewicz, Paweł; Łukaszewicz, Marcin

    2017-01-01

    It was proposed that magnetic fields (MFs) can influence gene transcription via CTCT motif located in human HSP70 promoter. To check the universality of this mechanism, we estimated the potential role of this motif on plant gene transcription in response to MFs using both bioinformatics and experimental studies. We searched potential promoter sequences (1000 bp upstream) in the potato Solanum tuberosum and thale cress Arabidopsis thaliana genomes for the CTCT sequence. The motif was found, on average, 3.6 and 4.3 times per promoter (148,487 and 134,361 motifs in total) in these two species, respectively; however, the CTCT sequences were not randomly distributed in the promoter regions but were preferentially located near the transcription initiation site and were closely packed. The closer these CTCT sequences to the transcription initiation site, the smaller distance between them in both plants. One can assume that genes with many CTCT motifs in their promoter regions can be potentially regulated by MFs. To check this assumption, we tested the influence of MFs on gene expression in a transgenic potato with three promoters (16R, 20R, and 5UGT) containing from 3 to 12 CTCT sequences and starting expression of β-glucuronidase as a reported gene. The potatoes were exposed to a 50 Hz 60–70 A/m MF for 30 min and the reporter gene activity was measured for up to 24 h. Although other factors induced the reporter gene activity, the MF did not. It implies the CTCT motif does not mediate in response to MF in the tested plant promoters. PMID:28326086

  12. Structural Relationships in the Lysozyme Superfamily: Significant Evidence for Glycoside Hydrolase Signature Motifs

    PubMed Central

    Wohlkönig, Alexandre; Huet, Joëlle; Looze, Yvan; Wintjens, René

    2010-01-01

    Background Chitin is a polysaccharide that forms the hard, outer shell of arthropods and the cell walls of fungi and some algae. Peptidoglycan is a polymer of sugars and amino acids constituting the cell walls of most bacteria. Enzymes that are able to hydrolyze these cell membrane polymers generally play important roles for protecting plants and animals against infection with insects and pathogens. A particular group of such glycoside hydrolase enzymes share some common features in their three-dimensional structure and in their molecular mechanism, forming the lysozyme superfamily. Results Besides having a similar fold, all known catalytic domains of glycoside hydrolase proteins of lysozyme superfamily (families and subfamilies GH19, GH22, GH23, GH24 and GH46) share in common two structural elements: the central helix of the all-α domain, which invariably contains the catalytic glutamate residue acting as general-acid catalyst, and a β-hairpin pointed towards the substrate binding cleft. The invariant β-hairpin structure is interestingly found to display the highest amino acid conservation in aligned sequences of a given family, thereby allowing to define signature motifs for each GH family. Most of such signature motifs are found to have promising performances for searching sequence databases. Our structural analysis further indicates that the GH motifs participate in enzymatic catalysis essentially by containing the catalytic water positioning residue of inverting mechanism. Conclusions The seven families and subfamilies of the lysozyme superfamily all have in common a β-hairpin structure which displays a family-specific sequence motif. These GH β-hairpin motifs contain potentially important residues for the catalytic activity, thereby suggesting the participation of the GH motif to catalysis and also revealing a common catalytic scheme utilized by enzymes of the lysozyme superfamily. PMID:21085702

  13. PhyloGibbs-MP: module prediction and discriminative motif-finding by Gibbs sampling.

    PubMed

    Siddharthan, Rahul

    2008-08-29

    PhyloGibbs, our recent Gibbs-sampling motif-finder, takes phylogeny into account in detecting binding sites for transcription factors in DNA and assigns posterior probabilities to its predictions obtained by sampling the entire configuration space. Here, in an extension called PhyloGibbs-MP, we widen the scope of the program, addressing two major problems in computational regulatory genomics. First, PhyloGibbs-MP can localise predictions to small, undetermined regions of a large input sequence, thus effectively predicting cis-regulatory modules (CRMs) ab initio while simultaneously predicting binding sites in those modules-tasks that are usually done by two separate programs. PhyloGibbs-MP's performance at such ab initio CRM prediction is comparable with or superior to dedicated module-prediction software that use prior knowledge of previously characterised transcription factors. Second, PhyloGibbs-MP can predict motifs that differentiate between two (or more) different groups of regulatory regions, that is, motifs that occur preferentially in one group over the others. While other "discriminative motif-finders" have been published in the literature, PhyloGibbs-MP's implementation has some unique features and flexibility. Benchmarks on synthetic and actual genomic data show that this algorithm is successful at enhancing predictions of differentiating sites and suppressing predictions of common sites and compares with or outperforms other discriminative motif-finders on actual genomic data. Additional enhancements include significant performance and speed improvements, the ability to use "informative priors" on known transcription factors, and the ability to output annotations in a format that can be visualised with the Generic Genome Browser. In stand-alone motif-finding, PhyloGibbs-MP remains competitive, outperforming PhyloGibbs-1.0 and other programs on benchmark data.

  14. An ion-responsive motif in the second transmembrane segment of rhodopsin-like receptors.

    PubMed

    Parker, M S; Wong, Y Y; Parker, S L

    2008-06-01

    A L(M)xxxD(N, E) motif (x=a non-ionic amino acid residue, most frequently A, S, L or F; small capitals indicating a minor representation) is found in the second transmembrane (tm2) segment of most G-protein coupling metazoan receptors of the rhodopsin family (Rh-GPCRs). Changes in signal transduction, agonist binding and receptor cycling are known for numerous receptors bearing evolved or experimentally introduced mutations in this tm2 motif, especially of its aspartate residue. The [Na(+)] sensitivity of the receptor-agonist interaction relates to this aspartate in a number of Rh-GPCRs. Native non-conservative mutations in the tm2 motif only rarely coincide with significant changes in two other ubiquitous features of the rhodopsin family, the seventh transmembrane N(D)PxxY(F) motif and the D(E)RY(W,F) or analogous sequence at the border of the third transmembrane helix and the second intracellular loop. Native tm2 mutations with Rh-GPCRs frequently result in constitutive signaling, and with visual opsins also in shifts to short-wavelength sensitivity. Substitution of a strongly basic residue for the tm2 aspartate in Taste-2 receptors could be connected to a lack of sodium sensing by these receptors. These properties could be consistent with ionic interactions, and even of ion transfer, that involve the tm2 motif. A decrease in cation sensing by this motif is usually connected to an enhanced constitutive interaction of the mutated receptors with cognate G- proteins, and also relates to both the constitutive and the overall activity of the short-wavelength opsins.

  15. Accurate Quantification of microRNA via Single Strand Displacement Reaction on DNA Origami Motif

    PubMed Central

    Lou, Jingyu; Li, Weidong; Li, Sheng; Zhu, Hongxin; Yang, Lun; Zhang, Aiping; He, Lin; Li, Can

    2013-01-01

    DNA origami is an emerging technology that assembles hundreds of staple strands and one single-strand DNA into certain nanopattern. It has been widely used in various fields including detection of biological molecules such as DNA, RNA and proteins. MicroRNAs (miRNAs) play important roles in post-transcriptional gene repression as well as many other biological processes such as cell growth and differentiation. Alterations of miRNAs' expression contribute to many human diseases. However, it is still a challenge to quantitatively detect miRNAs by origami technology. In this study, we developed a novel approach based on streptavidin and quantum dots binding complex (STV-QDs) labeled single strand displacement reaction on DNA origami to quantitatively detect the concentration of miRNAs. We illustrated a linear relationship between the concentration of an exemplary miRNA as miRNA-133 and the STV-QDs hybridization efficiency; the results demonstrated that it is an accurate nano-scale miRNA quantifier motif. In addition, both symmetrical rectangular motif and asymmetrical China-map motif were tested. With significant linearity in both motifs, our experiments suggested that DNA Origami motif with arbitrary shape can be utilized in this method. Since this DNA origami-based method we developed owns the unique advantages of simple, time-and-material-saving, potentially multi-targets testing in one motif and relatively accurate for certain impurity samples as counted directly by atomic force microscopy rather than fluorescence signal detection, it may be widely used in quantification of miRNAs. PMID:23990889

  16. Stable proline box motif at the N-terminal end of alpha-helices.

    PubMed Central

    Viguera, A. R.; Serrano, L.

    1999-01-01

    We describe a novel N-terminal alpha-helix local motif that involves three hydrophobic residues and a Pro residue (Pro-box motif). Database analysis shows that when Pro is the N-cap of an alpha-helix the distribution of amino acids in adjacent positions changes dramatically with respect to the average distribution in an alpha-helix, but not when Pro is at position N1. N-cap Pro residues are usually associated to Ile and Leu, at position N', Val at position N3 and a hydrophobic residue (h) at position N4. The side chain of the N-cap Pro packs against Val, while the hydrophobic residues at positions N' and N4 make favorable interactions. To analyze the role of this putative motif (sequence fingerprint hPXXhh), we have synthesized a series of peptides and analyzed them by circular dichroism (CD) and NMR. We find that this motif is formed in peptides, and that the accompanying hydrophobic interactions contribute up to 1.2 kcal/mol to helix stability. The fact that some of the residues in this fingerprint are not good N-cap and helix formers results in a small overall stabilization of the alpha-helix with respect to other peptides having Gly as the N-cap and Ala at N3 and N4. This suggests that the Pro-box motif will not specially contribute to protein stability but to the specificity of its fold. In fact, 80% of the sequences that contain the fingerprint sequence in the protein database are adopting the described structural motif, and in none of them is the helix extended to place Pro at the more favorable N1 position. PMID:10493574

  17. A systematic analysis of a mi-RNA inter-pathway regulatory motif

    PubMed Central

    2013-01-01

    Background The continuing discovery of new types and functions of small non-coding RNAs is suggesting the presence of regulatory mechanisms far more complex than the ones currently used to study and design Gene Regulatory Networks. Just focusing on the roles of micro RNAs (miRNAs), they have been found to be part of several intra-pathway regulatory motifs. However, inter-pathway regulatory mechanisms have been often neglected and require further investigation. Results In this paper we present the result of a systems biology study aimed at analyzing a high-level inter-pathway regulatory motif called Pathway Protection Loop, not previously described, in which miRNAs seem to play a crucial role in the successful behavior and activation of a pathway. Through the automatic analysis of a large set of public available databases, we found statistical evidence that this inter-pathway regulatory motif is very common in several classes of KEGG Homo Sapiens pathways and concurs in creating a complex regulatory network involving several pathways connected by this specific motif. The role of this motif seems also confirmed by a deeper review of other research activities on selected representative pathways. Conclusions Although previous studies suggested transcriptional regulation mechanism at the pathway level such as the Pathway Protection Loop, a high-level analysis like the one proposed in this paper is still missing. The understanding of higher-level regulatory motifs could, as instance, lead to new approaches in the identification of therapeutic targets because it could unveil new and “indirect” paths to activate or silence a target pathway. However, a lot of work still needs to be done to better uncover this high-level inter-pathway regulation including enlarging the analysis to other small non-coding RNA molecules. PMID:24152805

  18. A bioinformatics pipeline to search functional motifs within whole-proteome data: a case study of poxviruses.

    PubMed

    Sobhy, Haitham

    2017-04-01

    Proteins harbor domains or short linear motifs, which facilitate their functions and interactions. Finding functional motifs in protein sequences could predict the putative cellular roles or characteristics of hypothetical proteins. In this study, we present Shetti-Motif, which is an interactive tool to (i) map UniProt and PROSITE flat files, (ii) search for multiple pre-defined consensus patterns or experimentally validated functional motifs in large datasets protein sequences (proteome-wide), (iii) search for motifs containing repeated residues (low-complexity regions, e.g., Leu-, SR-, PEST-rich motifs, etc.). As proof of principle, using this comparative proteomics pipeline, eleven proteomes encoded by member of Poxviridae family were searched against about 100 experimentally validated functional motifs. The closely related viruses and viruses infect the same host cells (e.g. vaccinia and variola viruses) show similar motif-containing proteins profile. The motifs encoded by these viruses are correlated, which explains why poxviruses are able to interact with wide range of host cells. In conclusion, this in silico analysis is useful to establish a dataset(s) or potential proteins for further investigation or compare between species.

  19. AliBiMotif: integrating alignment and biclustering to unravel transcription factor binding sites in DNA sequences.

    PubMed

    Gonçalves, Joana P; Moreau, Yves; Madeira, Sara C

    2012-01-01

    Transcription Factors (TFs) control transcription by binding to specific sites in the promoter regions of the target genes, which can be modelled by structured motifs. In this paper we propose AliBiMotif, a method combining sequence alignment and a biclustering approach based on efficient string matching techniques using suffix trees to unravel approximately conserved sets of blocks (structured motifs) while straightforwardly disregarding non-conserved stretches in-between. The ability to ignore the width of non-conserved regions is a major advantage of the proposed method over other motif finders, as the lengths of the binding sites are usually easier to estimate than the separating distances.

  20. The MASH pipeline for protein function prediction and an algorithm for the geometric refinement of 3D motifs.

    PubMed

    Chen, Brian Y; Fofanov, Viacheslav Y; Bryant, Drew H; Dodson, Bradley D; Kristensen, David M; Lisewski, Andreas M; Kimmel, Marek; Lichtarge, Olivier; Kavraki, Lydia E

    2007-01-01

    The development of new and effective drugs is strongly affected by the need to identify drug targets and to reduce side effects. Resolving these issues depends partially on a thorough understanding of the biological function of proteins. Unfortunately, the experimental determination of protein function is expensive and time consuming. To support and accelerate the determination of protein functions, algorithms for function prediction are designed to gather evidence indicating functional similarity with well studied proteins. One such approach is the MASH pipeline, described in the first half of this paper. MASH identifies matches of geometric and chemical similarity between motifs, representing known functional sites, and substructures of functionally uncharacterized proteins (targets). Observations from several research groups concur that statistically significant matches can indicate functionally related active sites. One major subproblem is the design of effective motifs, which have many matches to functionally related targets (sensitive motifs), and few matches to functionally unrelated targets (specific motifs). Current techniques select and combine structural, physical, and evolutionary properties to generate motifs that mirror functional characteristics in active sites. This approach ignores incidental similarities that may occur with functionally unrelated proteins. To address this problem, we have developed Geometric Sieving (GS), a parallel distributed algorithm that efficiently refines motifs, designed by existing methods, into optimized motifs with maximal geometric and chemical dissimilarity from all known protein structures. In exhaustive comparison of all possible motifs based on the active sites of 10 well-studied proteins, we observed that optimized motifs were among the most sensitive and specific.

  1. Classification of protein motifs based on subcellular localization uncovers evolutionary relationships at both sequence and functional levels

    PubMed Central

    2013-01-01

    Background Most proteins have evolved in specific cellular compartments that limit their functions and potential interactions. On the other hand, motifs define amino acid arrangements conserved between protein family members and represent powerful tools for assigning function to protein sequences. The ideal motif would identify all members of a protein family but in practice many motifs identify both family members and unrelated proteins, referred to as True Positive (TP) and False Positive (FP) sequences, respectively. Results To address the relationship between protein motifs, protein function and cellular localization, we systematically assigned subcellular localization data to motif sequences from the comprehensive PROSITE sequence motif database. Using this data we analyzed relationships between localization and function. We find that TPs and FPs have a strong tendency to localize in different compartments. When multiple localizations are considered, TPs are usually distributed between related cellular compartments. We also identified cases where FPs are concentrated in particular subcellular regions, indicating possible functional or evolutionary relationships with TP sequences of the same motif. Conclusions Our findings suggest that the systematic examination of subcellular localization has the potential to uncover evolutionary and functional relationships between motif-containing sequences. We believe that this type of analysis complements existing motif annotations and could aid in their interpretation. Our results shed light on the evolution of cellular organelles and potentially establish the basis for new subcellular localization and function prediction algorithms. PMID:23865897

  2. Cloud-based MOTIFSIM: Detecting Similarity in Large DNA Motif Data Sets.

    PubMed

    Tran, Ngoc Tam L; Huang, Chun-Hsi

    2016-09-08

    We developed the cloud-based MOTIFSIM on Amazon Web Services (AWS) cloud. The tool is an extended version from our web-based tool version 2.0, which was developed based on a novel algorithm for detecting similarity in multiple DNA motif data sets. This cloud-based version further allows researchers to exploit the computing resources available from AWS to detect similarity in multiple large-scale DNA motif data sets resulting from the next-generation sequencing technology. The tool is highly scalable with expandable AWS.

  3. Identification of an oligodeoxynucleotide sequence motif that specifically inhibits phosphorylation by protein tyrosine kinases.

    PubMed

    Krieg, A M; Matson, S; Cheng, K; Fisher, E; Koretzky, G A; Koland, J G

    1997-04-01

    Protein tyrosine kinases (PTKs) have central roles in cellular signal transduction. We have identified a sequence motif (CGT[C]GA) in phosphorothioate-modified oligodeoxynucleotides (ODNs) that specifically inhibits the enzymatic activity of recombinant or immunoprecipitated PTK in vitro. Hexamer ODNs containing this motif block both substrate and autophosphorylation of at least four different PTKs but have no apparent effect on the enzymatic activity of a serine/threonine protein kinase. These data suggest possible new applications for ODNs and have implications for the design and interpretation of experiments using antisense or triplex ODNs.

  4. Novel motifs distinguish multiple homologues of Polycomb in vertebrates: expansion and diversification of the epigenetic toolkit

    PubMed Central

    2009-01-01

    Background Polycomb group (PcG) proteins maintain expression pattern of genes set early during development. Although originally isolated as regulators of homeotic genes, PcG members play a key role in epigenetic mechanism that maintains the expression state of a large number of genes. Polycomb (PC) is conserved during evolution and while invertebrates have one PC gene, vertebrates have five or more homologues. It remains unclear if different vertebrate PC homologues have distinct or overlapping functions. We have identified and compared the sequence of PC homologues in various organisms to analyze similarities and differences that shaped the evolutionary history of this key regulatory protein. Results All PC homologues have an N-terminal chromodomain and a C-terminal Polycomb Repressor box. We searched the protein and genome sequence database of various organisms for these signatures and identified ~100 PC homologues. Comparative analysis of these sequences led to the identification of a novel insect specific motif and several novel and signature motifs in the vertebrate homologue: two in CBX2 (Cx2.1 and Cx2.2), four in CBX4 (Cx4.1, Cx4.2, Cx4.3 and Cx4.4), three in CBX6 (Cx6.1, Cx6.2 and Cx6.3) and one in CBX8 (Cx8.1). Additionally, adjacent to the chromodomain, all the vertebrate homologues have a DNA binding motif - AT-Hook in case of CBX2, which was known earlier, and 'AT-Hook Like' motif, from this study, in other PC homologues. Conclusion Our analysis shows that PC is an ancient gene dating back to pre bilaterian origin that has not only been conserved but has also expanded during the evolution of complexity. Unique motifs acquired by each homologue have been maintained for more than 500 millions years indicating their functional relevance in boosting the epigenetic 'tool kit'. We report the presence of a DNA interaction motif adjacent to chromodomain in all vertebrate PC homologues and suggest a three-way 'PC-histoneH3-DNA' interaction that can restrict

  5. BetaSearch: a new method for querying β-residue motifs

    PubMed Central

    2012-01-01

    Background Searching for structural motifs across known protein structures can be useful for identifying unrelated proteins with similar function and characterising secondary structures such as β-sheets. This is infeasible using conventional sequence alignment because linear protein sequences do not contain spatial information. β-residue motifs are β-sheet substructures that can be represented as graphs and queried using existing graph indexing methods, however, these approaches are designed for general graphs that do not incorporate the inherent structural constraints of β-sheets and require computationally-expensive filtering and verification procedures. 3D substructure search methods, on the other hand, allow β-residue motifs to be queried in a three-dimensional context but at significant computational costs. Findings We developed a new method for querying β-residue motifs, called BetaSearch, which leverages the natural planar constraints of β-sheets by indexing them as 2D matrices, thus avoiding much of the computational complexities involved with structural and graph querying. BetaSearch exhibits faster filtering, verification, and overall query time than existing graph indexing approaches whilst producing comparable index sizes. Compared to 3D substructure search methods, BetaSearch achieves 33 and 240 times speedups over index-based and pairwise alignment-based approaches, respectively. Furthermore, we have presented case-studies to demonstrate its capability of motif matching in sequentially dissimilar proteins and described a method for using BetaSearch to predict β-strand pairing. Conclusions We have demonstrated that BetaSearch is a fast method for querying substructure motifs. The improvements in speed over existing approaches make it useful for efficiently performing high-volume exploratory querying of possible protein substructural motifs or conformations. BetaSearch was used to identify a nearly identical β-residue motif between an entirely

  6. Incorporating Motif Analysis into Gene Co-expression Networks Reveals Novel Modular Expression Pattern and New Signaling Pathways

    PubMed Central

    Ma, Shisong; Shah, Smit; Bohnert, Hans J.; Snyder, Michael; Dinesh-Kumar, Savithramma P.

    2013-01-01

    Understanding of gene regulatory networks requires discovery of expression modules within gene co-expression networks and identification of promoter motifs and corresponding transcription factors that regulate their expression. A commonly used method for this purpose is a top-down approach based on clustering the network into a range of densely connected segments, treating these segments as expression modules, and extracting promoter motifs from these modules. Here, we describe a novel bottom-up approach to identify gene expression modules driven by known cis-regulatory motifs in the gene promoters. For a specific motif, genes in the co-expression network are ranked according to their probability of belonging to an expression module regulated by that motif. The ranking is conducted via motif enrichment or motif position bias analysis. Our results indicate that motif position bias analysis is an effective tool for genome-wide motif analysis. Sub-networks containing the top ranked genes are extracted and analyzed for inherent gene expression modules. This approach identified novel expression modules for the G-box, W-box, site II, and MYB motifs from an Arabidopsis thaliana gene co-expression network based on the graphical Gaussian model. The novel expression modules include those involved in house-keeping functions, primary and secondary metabolism, and abiotic and biotic stress responses. In addition to confirmation of previously described modules, we identified modules that include new signaling pathways. To associate transcription factors that regulate genes in these co-expression modules, we developed a novel reporter system. Using this approach, we evaluated MYB transcription factor-promoter interactions within MYB motif modules. PMID:24098147

  7. S-layer homology motif is an immunogen and confers protection to mouse model against anthrax.

    PubMed

    Kulshreshtha, Parul; Aggarwal, Sneha; Jaiswal, Hemant; Bhatnagar, Rakesh

    2012-02-01

    SLH proteins bear an S-layer homology motif comprised of three S-layer homology (SLH) domains. Several SLH proteins in Bacillus anthracis have been recognized as immunogenic in recent past. We hypothesized that the SLH motif, the most common moiety amongst all the SLH proteins could be responsible for their immunogenicity. To test this hypothesis, we checked the immunogenic capacity of recombinant SLH motif. The rSLH fragment on immunization in mice led to the development of a potent humoral and T Helper immune response as compared to the only adjuvant immunized group. Antibodies raised against rSLH could identify the surface of B. anthracis Ames strain vegetative forms. rSLH immunization protected 50% mice challenged with B. anthracis compared to 0% survival in group of mice immunized with only adjuvant. But when rSLH immunization was synergized with a single sub-optimal dose of rPA (Protective Antigen), 80% immunized mice survived the lethal challenge of B. anthracis. Taken together, for the first time we demonstrate the immunogenic and protective potential of SLH motif of the SLH proteins of B. anthracis.

  8. Cellular microRNAs up-regulate transcription via interaction with promoter TATA-box motifs.

    PubMed

    Zhang, Yijun; Fan, Miaomiao; Zhang, Xue; Huang, Feng; Wu, Kang; Zhang, Junsong; Liu, Jun; Huang, Zhuoqiong; Luo, Haihua; Tao, Liang; Zhang, Hui

    2014-12-01

    The TATA box represents one of the most prevalent core promoters where the pre-initiation complexes (PICs) for gene transcription are assembled. This assembly is crucial for transcription initiation and well regulated. Here we show that some cellular microRNAs (miRNAs) are associated with RNA polymerase II (Pol II) and TATA box-binding protein (TBP) in human peripheral blood mononuclear cells (PBMCs). Among them, let-7i sequence specifically binds to the TATA-box motif of interleukin-2 (IL-2) gene and elevates IL-2 mRNA and protein production in CD4(+) T-lymphocytes in vitro and in vivo. Through direct interaction with the TATA-box motif, let-7i facilitates the PIC assembly and transcription initiation of IL-2 promoter. Several other cellular miRNAs, such as mir-138, mir-92a or mir-181d, also enhance the promoter activities via binding to the TATA-box motifs of insulin, calcitonin or c-myc, respectively. In agreement with the finding that an HIV-1-encoded miRNA could enhance viral replication through targeting the viral promoter TATA-box motif, our data demonstrate that the interaction with core transcription machinery is a novel mechanism for miRNAs to regulate gene expression.

  9. Application of motif-based tools on evolutionary analysis of multipartite single-stranded DNA viruses.

    PubMed

    Wang, Hsiang-Iu; Chang, Chih-Hung; Lin, Po-Heng; Fu, Hui-Chuan; Tang, Chuanyi; Yeh, Hsin-Hung

    2013-01-01

    Multipartite viruses contain more than one distinctive genome component, and the origin of multipartite viruses has been suggested to evolve from a non-segmented wild-type virus. To explore whether recombination also plays a role in the evolution of the genomes of multipartite viruses, we developed a systematic approach that employs motif-finding tools to detect conserved motifs from divergent genomic regions and applies statistical approaches to select high-confidence motifs. The information that this approach provides helps us understand the evolution of viruses. In this study, we compared our motif-based strategy with current alignment-based recombination-detecting methods and applied our methods to the analysis of multipartite single-stranded plant DNA viruses, including bipartite begomoviruses, Banana bunchy top virus (BBTV) (consisting of 6 genome components) and Faba bean necrotic yellows virus (FBNYV) (consisting of 8 genome components). Our analysis revealed that recombination occurred between genome components in some begomoviruses, BBTV and FBNYV. Our data also show that several unusual recombination events have contributed to the evolution of BBTV genome components. We believe that similar approaches can be applied to resolve the evolutionary history of other viruses.

  10. Using machine learning to predict gene expression and discover sequence motifs

    NASA Astrophysics Data System (ADS)

    Li, Xuejing

    Recently, large amounts of experimental data for complex biological systems have become available. We use tools and algorithms from machine learning to build data-driven predictive models. We first present a novel algorithm to discover gene sequence motifs associated with temporal expression patterns of genes. Our algorithm, which is based on partial least squares (PLS) regression, is able to directly model the flow of information, from gene sequence to gene expression, to learn cis regulatory motifs and characterize associated gene expression patterns. Our algorithm outperforms traditional computational methods e.g. clustering in motif discovery. We then present a study of extending a machine learning model for transcriptional regulation predictive of genetic regulatory response to Caenorhabditis elegans. We show meaningful results both in terms of prediction accuracy on the test experiments and biological information extracted from the regulatory program. The model discovers DNA binding sites ab initio. We also present a case study where we detect a signal of lineage-specific regulation. Finally we present a comparative study on learning predictive models for motif discovery, based on different boosting algorithms: Adaptive Boosting (AdaBoost), Linear Programming Boosting (LPBoost) and Totally Corrective Boosting (TotalBoost). We evaluate and compare the performance of the three boosting algorithms via both statistical and biological validation, for hypoxia response in Saccharomyces cerevisiae.

  11. ML2Motif—Reliable extraction of discriminative sequence motifs from learning machines

    PubMed Central

    Kloft, Marius; Müller, Klaus-Robert; Görnitz, Nico

    2017-01-01

    High prediction accuracies are not the only objective to consider when solving problems using machine learning. Instead, particular scientific applications require some explanation of the learned prediction function. For computational biology, positional oligomer importance matrices (POIMs) have been successfully applied to explain the decision of support vector machines (SVMs) using weighted-degree (WD) kernels. To extract relevant biological motifs from POIMs, the motifPOIM method has been devised and showed promising results on real-world data. Our contribution in this paper is twofold: as an extension to POIMs, we propose gPOIM, a general measure of feature importance for arbitrary learning machines and feature sets (including, but not limited to, SVMs and CNNs) and devise a sampling strategy for efficient computation. As a second contribution, we derive a convex formulation of motifPOIMs that leads to more reliable motif extraction from gPOIMs. Empirical evaluations confirm the usefulness of our approach on artificially generated data as well as on real-world datasets. PMID:28346487

  12. Bayesian Markov models consistently outperform PWMs at predicting motifs in nucleotide sequences

    PubMed Central

    Siebert, Matthias; Söding, Johannes

    2016-01-01

    Position weight matrices (PWMs) are the standard model for DNA and RNA regulatory motifs. In PWMs nucleotide probabilities are independent of nucleotides at other positions. Models that account for dependencies need many parameters and are prone to overfitting. We have developed a Bayesian approach for motif discovery using Markov models in which conditional probabilities of order k − 1 act as priors for those of order k. This Bayesian Markov model (BaMM) training automatically adapts model complexity to the amount of available data. We also derive an EM algorithm for de-novo discovery of enriched motifs. For transcription factor binding, BaMMs achieve significantly (P    =  1/16) higher cross-validated partial AUC than PWMs in 97% of 446 ChIP-seq ENCODE datasets and improve performance by 36% on average. BaMMs also learn complex multipartite motifs, improving predictions of transcription start sites, polyadenylation sites, bacterial pause sites, and RNA binding sites by 26–101%. BaMMs never performed worse than PWMs. These robust improvements argue in favour of generally replacing PWMs by BaMMs. PMID:27288444

  13. The MRE11 GAR motif regulates DNA double-strand break processing and ATR activation

    PubMed Central

    Yu, Zhenbao; Vogel, Gillian; Coulombe, Yan; Dubeau, Danielle; Spehalski, Elizabeth; Hébert, Josée; Ferguson, David O; Masson, Jean Yves; Richard, Stéphane

    2012-01-01

    The MRE11/RAD50/NBS1 complex is the primary sensor rapidly recruited to DNA double-strand breaks (DSBs). MRE11 is known to be arginine methylated by PRMT1 within its glycine-arginine-rich (GAR) motif. In this study, we report a mouse knock-in allele of Mre11 that substitutes the arginines with lysines in the GAR motif and generates the MRE11RK protein devoid of methylated arginines. The Mre11RK/RK mice were hypersensitive to γ-irradiation (IR) and the cells from these mice displayed cell cycle checkpoint defects and chromosome instability. Moreover, the Mre11RK/RK MEFs exhibited ATR/CHK1 signaling defects and impairment in the recruitment of RPA and RAD51 to the damaged sites. The MRKRN complex formed and localized to the sites of DNA damage and normally activated the ATM pathway in response to IR. The MRKRN complex exhibited exonuclease and DNA-binding defects in vitro responsible for the impaired DNA end resection and ATR activation observed in vivo in response to IR. Our findings provide genetic evidence for the critical role of the MRE11 GAR motif in DSB repair, and demonstrate a mechanistic link between post-translational modifications at the MRE11 GAR motif and DSB processing, as well as the ATR/CHK1 checkpoint signaling. PMID:21826105

  14. Exploiting Publicly Available Biological and Biochemical Information for the Discovery of Novel Short Linear Motifs

    PubMed Central

    Sayadi, Ahmed; Briganti, Leonardo; Tramontano, Anna; Via, Allegra

    2011-01-01

    The function of proteins is often mediated by short linear segments of their amino acid sequence, called Short Linear Motifs or SLiMs, the identification of which can provide important information about a protein function. However, the short length of the motifs and their variable degree of conservation makes their identification hard since it is difficult to correctly estimate the statistical significance of their occurrence. Consequently, only a small fraction of them have been discovered so far. We describe here an approach for the discovery of SLiMs based on their occurrence in evolutionarily unrelated proteins belonging to the same biological, signalling or metabolic pathway and give specific examples of its effectiveness in both rediscovering known motifs and in discovering novel ones. An automatic implementation of the procedure, available for download, allows significant motifs to be identified, automatically annotated with functional, evolutionary and structural information and organized in a database that can be inspected and queried. An instance of the database populated with pre-computed data on seven organisms is accessible through a publicly available server and we believe it constitutes by itself a useful resource for the life sciences (http://www.biocomputing.it/modipath). PMID:21799808

  15. Computational identification and functional validation of regulatory motifs in cartilage-expressed genes

    PubMed Central

    Davies, Sherri R.; Chang, Li-Wei; Patra, Debabrata; Xing, Xiaoyun; Posey, Karen; Hecht, Jacqueline; Stormo, Gary D.; Sandell, Linda J.

    2007-01-01

    Chondrocyte gene regulation is important for the generation and maintenance of cartilage tissues. Several regulatory factors have been identified that play a role in chondrogenesis, including the positive transacting factors of the SOX family such as SOX9, SOX5, and SOX6, as well as negative transacting factors such as C/EBP and delta EF1. However, a complete understanding of the intricate regulatory network that governs the tissue-specific expression of cartilage genes is not yet available. We have taken a computational approach to identify cis-regulatory, transcription factor (TF) binding motifs in a set of cartilage characteristic genes to better define the transcriptional regulatory networks that regulate chondrogenesis. Our computational methods have identified several TFs, whose binding profiles are available in the TRANSFAC database, as important to chondrogenesis. In addition, a cartilage-specific SOX-binding profile was constructed and used to identify both known, and novel, functional paired SOX-binding motifs in chondrocyte genes. Using DNA pattern-recognition algorithms, we have also identified cis-regulatory elements for unknown TFs. We have validated our computational predictions through mutational analyses in cell transfection experiments. One novel regulatory motif, N1, found at high frequency in the COL2A1 promoter, was found to bind to chondrocyte nuclear proteins. Mutational analyses suggest that this motif binds a repressive factor that regulates basal levels of the COL2A1 promoter. PMID:17785538

  16. A conserved motif of vertebrate Y RNAs essential for chromosomal DNA replication

    PubMed Central

    Gardiner, Timothy J.; Christov, Christo P.; Langley, Alexander R.; Krude, Torsten

    2009-01-01

    Noncoding Y RNAs are required for the reconstitution of chromosomal DNA replication in late G1 phase template nuclei in a human cell-free system. Y RNA genes are present in all vertebrates and in some isolated nonvertebrates, but the conservation of Y RNA function and key determinants for its function are unknown. Here, we identify a determinant of Y RNA function in DNA replication, which is conserved throughout vertebrate evolution. Vertebrate Y RNAs are able to reconstitute chromosomal DNA replication in the human cell-free DNA replication system, but nonvertebrate Y RNAs are not. A conserved nucleotide sequence motif in the double-stranded stem of vertebrate Y RNAs correlates with Y RNA function. A functional screen of human Y1 RNA mutants identified this conserved motif as an essential determinant for reconstituting DNA replication in vitro. Double-stranded RNA oligonucleotides comprising this RNA motif are sufficient to reconstitute DNA replication, but corresponding DNA or random sequence RNA oligonucleotides are not. In intact cells, wild-type hY1 or the conserved RNA duplex can rescue an inhibition of DNA replication after RNA interference against hY3 RNA. Therefore, we have identified a new RNA motif that is conserved in vertebrate Y RNA evolution, and essential and sufficient for Y RNA function in human chromosomal DNA replication. PMID:19474146

  17. Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif

    PubMed Central

    Hernández-Sánchez, Itzell E.; Maruri-López, Israel; Ferrando, Alejandro; Carbonell, Juan; Graether, Steffen P.; Jiménez-Bremont, Juan F.

    2015-01-01

    The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization. PMID:26442018

  18. Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif.

    PubMed

    Hernández-Sánchez, Itzell E; Maruri-López, Israel; Ferrando, Alejandro; Carbonell, Juan; Graether, Steffen P; Jiménez-Bremont, Juan F

    2015-01-01

    The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization.

  19. Identification of sequence–structure RNA binding motifs for SELEX-derived aptamers

    PubMed Central

    Hoinka, Jan; Zotenko, Elena; Friedman, Adam; Sauna, Zuben E.; Przytycka, Teresa M.

    2012-01-01

    Motivation: Systematic Evolution of Ligands by EXponential Enrichment (SELEX) represents a state-of-the-art technology to isolate single-stranded (ribo)nucleic acid fragments, named aptamers, which bind to a molecule (or molecules) of interest via specific structural regions induced by their sequence-dependent fold. This powerful method has applications in designing protein inhibitors, molecular detection systems, therapeutic drugs and antibody replacement among others. However, full understanding and consequently optimal utilization of the process has lagged behind its wide application due to the lack of dedicated computational approaches. At the same time, the combination of SELEX with novel sequencing technologies is beginning to provide the data that will allow the examination of a variety of properties of the selection process. Results: To close this gap we developed, Aptamotif, a computational method for the identification of sequence–structure motifs in SELEX-derived aptamers. To increase the chances of identifying functional motifs, Aptamotif uses an ensemble-based approach. We validated the method using two published aptamer datasets containing experimentally determined motifs of increasing complexity. We were able to recreate the author's findings to a high degree, thus proving the capability of our approach to identify binding motifs in SELEX data. Additionally, using our new experimental dataset, we illustrate the application of Aptamotif to elucidate several properties of the selection process. Contact: przytyck@ncbi.nlm.nih.gov, Zuben.Sauna@fda.hhs.gov PMID:22689764

  20. Numb directs the subcellular localization of EAAT3 through binding the YxNxxF motif.

    PubMed

    Su, Jin-Feng; Wei, Jian; Li, Pei-Shan; Miao, Hong-Hua; Ma, Yong-Chao; Qu, Yu-Xiu; Xu, Jie; Qin, Jie; Li, Bo-Liang; Song, Bao-Liang; Xu, Zheng-Ping; Luo, Jie

    2016-08-15

    Excitatory amino acid transporter type 3 (EAAT3, also known as SLC1A1) is a high-affinity, Na(+)-dependent glutamate carrier that localizes primarily within the cell and at the apical plasma membrane. Although previous studies have reported proteins and sequence regions involved in EAAT3 trafficking, the detailed molecular mechanism by which EAAT3 is distributed to the correct location still remains elusive. Here, we identify that the YVNGGF sequence in the C-terminus of EAAT3 is responsible for its intracellular localization and apical sorting in rat hepatoma cells CRL1601 and Madin-Darby canine kidney (MDCK) cells, respectively. We further demonstrate that Numb, a clathrin adaptor protein, directly binds the YVNGGF motif and regulates the localization of EAAT3. Mutation of Y503, N505 and F508 within the YVNGGF motif to alanine residues or silencing Numb by use of small interfering RNA (siRNA) results in the aberrant localization of EAAT3. Moreover, both Numb and the YVNGGF motif mediate EAAT3 endocytosis in CRL1601 cells. In summary, our study suggests that Numb is a pivotal adaptor protein that mediates the subcellular localization of EAAT3 through binding the YxNxxF (where x stands for any amino acid) motif.

  1. Identification of a binding motif specific to HNF4 by comparative analysis of multiple nuclear receptors

    PubMed Central

    Fang, Bin; Mane-Padros, Daniel; Bolotin, Eugene; Jiang, Tao; Sladek, Frances M.

    2012-01-01

    Nuclear receptors (NRs) regulate gene expression by binding specific DNA sequences consisting of AG[G/T]TCA or AGAACA half site motifs in a variety of configurations. However, those motifs/configurations alone do not adequately explain the diversity of NR function in vivo. Here, a systematic examination of DNA binding specificity by protein-binding microarrays (PBMs) of three closely related human NRs—HNF4α, retinoid X receptor alpha (RXRα) and COUPTF2—reveals an HNF4-specific binding motif (H4-SBM), xxxxCAAAGTCCA, as well as a previously unrecognized polarity in the classical DR1 motif (AGGTCAxAGGTCA) for HNF4α, RXRα and COUPTF2 homodimers. ChIP-seq data indicate that the H4-SBM is uniquely bound by HNF4α but not 10 other NRs in vivo, while NRs PXR, FXRα, Rev-Erbα appear to bind adjacent to H4-SBMs. HNF4-specific DNA recognition and transactivation are mediated by residues Asp69 and Arg76 in the DNA-binding domain; this combination of amino acids is unique to HNF4 among all human NRs. Expression profiling and ChIP data predict ∼100 new human HNF4α target genes with an H4-SBM site, including several Co-enzyme A-related genes and genes with links to disease. These results provide important new insights into NR DNA binding. PMID:22383578

  2. Bayesian models and Markov chain Monte Carlo methods for protein motifs with the secondary characteristics.

    PubMed

    Xie, Jun; Kim, Nak-Kyeong

    2005-09-01

    Statistical methods have been developed for finding local patterns, also called motifs, in multiple protein sequences. The aligned segments may imply functional or structural core regions. However, the existing methods often have difficulties in aligning multiple proteins when sequence residue identities are low (e.g., less than 25%). In this article, we develop a Bayesian model and Markov chain Monte Carlo (MCMC) methods for identifying subtle motifs in protein sequences. Specifically, a motif is defined not only in terms of specific sites characterized by amino acid frequency vectors, but also as a combination of secondary characteristics such as hydrophobicity, polarity, etc. Markov chain Monte Carlo methods are proposed to search for a motif pattern with high posterior probability under the new model. A special MCMC algorithm is developed, involving transitions between state spaces of different dimensions. The proposed methods were supported by a simulated study. It was then tested by two real datasets, including a group of helix-turn-helix proteins, and one set from the CATH Protein Structure Classification Database. Statistical comparisons showed that the new approach worked better than a typical Gibbs sampling approach which is based only on an amino acid model.

  3. Succession of Alkane Conformational Motifs Bound within Hydrophobic Supramolecular Capsular Assemblies.

    PubMed

    Barnett, J Wesley; Gibb, Bruce C; Ashbaugh, Henry S

    2016-10-06

    n-Alkane encapsulation experiments within dimeric octa-acid cavitand capsules in water reveal a succession of packing motifs from extended, to helical, to hairpin, to spinning top structures with increasing chain length. Here, we report a molecular simulation study of alkane conformational preferences within these host-guest assemblies to uncover the factors stabilizing distinct conformers. The simulated alkane conformers follow the trends inferred from (1)H NMR experiments, while guest proton chemical shifts evaluated from Gauge Invariant Atomic Orbital calculations provide further evidence our simulations capture guest packing within these assemblies. Analysis of chain length and dihedral distributions indicates that packing under confinement to minimize nonpolar guest and host interior contact with water largely drives the transitions. Mean intramolecular distance maps and transfer free energy differences suggest the extended and helical motifs are members of a larger family of linear guest structures, for which the guest gauche population increases with increasing chain length to accommodate the chains within the complex. Breaks observed between the helical/hairpin and hairpin/spinning top motifs, on the other hand, indicate the hairpin and spinning top conformations are distinct from the linear family. Our results represent the first bridging of empirical and simulation data for flexible guests encapsulated within confined nanospaces, and constitute an effective strategy by which guest packing motifs within artificial or natural compartments can be rationalized and/or predicted a priori.

  4. Analysis of tetra- and hepta-nucleotides motifs promoting -1 ribosomal frameshifting in Escherichia coli

    PubMed Central

    Sharma, Virag; Prère, Marie-Françoise; Canal, Isabelle; Firth, Andrew E.; Atkins, John F.; Baranov, Pavel V.; Fayet, Olivier

    2014-01-01

    Programmed ribosomal -1 frameshifting is a non-standard decoding process occurring when ribosomes encounter a signal embedded in the mRNA of certain eukaryotic and prokaryotic genes. This signal has a mandatory component, the frameshift motif: it is either a Z_ZZN tetramer or a X_XXZ_ZZN heptamer (where ZZZ and XXX are three identical nucleotides) allowing cognate or near-cognate repairing to the -1 frame of the A site or A and P sites tRNAs. Depending on the signal, the frameshifting frequency can vary over a wide range, from less than 1% to more than 50%. The present study combines experimental and bioinformatics approaches to carry out (i) a systematic analysis of the frameshift propensity of all possible motifs (16 Z_ZZN tetramers and 64 X_XXZ_ZZN heptamers) in Escherichia coli and (ii) the identification of genes potentially using this mode of expression amongst 36 Enterobacteriaceae genomes. While motif efficiency varies widely, a major distinctive rule of bacterial -1 frameshifting is that the most efficient motifs are those allowing cognate re-pairing of the A site tRNA from ZZN to ZZZ. The outcome of the genomic search is a set of 69 gene clusters, 59 of which constitute new candidates for functional utilization of -1 frameshifting. PMID:24875478

  5. A cell-surface-anchored ratiometric i-motif sensor for extracellular pH detection.

    PubMed

    Ying, Le; Xie, Nuli; Yang, Yanjing; Yang, Xiaohai; Zhou, Qifeng; Yin, Bincheng; Huang, Jin; Wang, Kemin

    2016-06-14

    A FRET-based sensor is anchored on the cell surface through streptavidin-biotin interactions. Due to the excellent properties of the pH-sensitive i-motif structure, the sensor can detect extracellular pH with high sensitivity and excellent reversibility.

  6. Motif analysis in directed ordered networks and applications to food webs

    PubMed Central

    Paulau, Pavel V.; Feenders, Christoph; Blasius, Bernd

    2015-01-01

    The analysis of small recurrent substructures, so called network motifs, has become a standard tool of complex network science to unveil the design principles underlying the structure of empirical networks. In many natural systems network nodes are associated with an intrinsic property according to which they can be ordered and compared against each other. Here, we expand standard motif analysis to be able to capture the hierarchical structure in such ordered networks. Our new approach is based on the identification of all ordered 3-node substructures and the visualization of their significance profile. We present a technique to calculate the fine grained motif spectrum by resolving the individual members of isomorphism classes (sets of substructures formed by permuting node-order). We apply this technique to computer generated ensembles of ordered networks and to empirical food web data, demonstrating the importance of considering node order for food-web analysis. Our approach may not only be helpful to identify hierarchical patterns in empirical food webs and other natural networks, it may also provide the base for extending motif analysis to other types of multi-layered networks. PMID:26144248

  7. [Conserved motifs in the primary and secondary ITS1 structures in bryophytes].

    PubMed

    Milyutina, I A; Ignatov, M S

    2015-01-01

    A study of the ITS1 nucleotide sequences of 1000 moss species of 62 families, 11 liverwort species from five orders, and one hornwort Anthoceros agrestis identified five highly conserved motifs (CM1-CM5), which are presumably involved in pre-rRNA processing. Although the ITS1 sequences substantially differ in length and the extent of divergence, the conserved motifs are found in all of them. ITS1 secondary structures were constructed for 76 mosses, and main regularities at conserved motif positioning were observed. The positions of processing sites in the ITS1 secondary structure of the yeast Saccharomyces cerevisiae were found to be similar to the positions of the conserved motifs in the ITS1 secondary structures of mosses and liverworts. In addition, a potential hairpin formation in the putative secondary structure of a pre-rRNA fragment was considered for the region between ITS1 CM4-CM5 and a highly conserved region between hairpins 49 and 50 (H49 and H50) of the 18S rRNA.

  8. Crystal structure of SEL1L: Insight into the roles of SLR motifs in ERAD pathway

    PubMed Central

    Jeong, Hanbin; Sim, Hyo Jung; Song, Eun Kyung; Lee, Hakbong; Ha, Sung Chul; Jun, Youngsoo; Park, Tae Joo; Lee, Changwook

    2016-01-01

    Terminally misfolded proteins are selectively recognized and cleared by the endoplasmic reticulum-associated degradation (ERAD) pathway. SEL1L, a component of the ERAD machinery, plays an important role in selecting and transporting ERAD substrates for degradation. We have determined the crystal structure of the mouse SEL1L central domain comprising five Sel1-Like Repeats (SLR motifs 5 to 9; hereafter called SEL1Lcent). Strikingly, SEL1Lcent forms a homodimer with two-fold symmetry in a head-to-tail manner. Particularly, the SLR motif 9 plays an important role in dimer formation by adopting a domain-swapped structure and providing an extensive dimeric interface. We identified that the full-length SEL1L forms a self-oligomer through the SEL1Lcent domain in mammalian cells. Furthermore, we discovered that the SLR-C, comprising SLR motifs 10 and 11, of SEL1L directly interacts with the N-terminus luminal loops of HRD1. Therefore, we propose that certain SLR motifs of SEL1L play a unique role in membrane bound ERAD machinery. PMID:27064360

  9. ATtRACT-a database of RNA-binding proteins and associated motifs.

    PubMed

    Giudice, Girolamo; Sánchez-Cabo, Fátima; Torroja, Carlos; Lara-Pezzi, Enrique

    2016-01-01

    RNA-binding proteins (RBPs) play a crucial role in key cellular processes, including RNA transport, splicing, polyadenylation and stability. Understanding the interaction between RBPs and RNA is key to improve our knowledge of RNA processing, localization and regulation in a global manner. Despite advances in recent years, a unified non-redundant resource that includes information on experimentally validated motifs, RBPs and integrated tools to exploit this information is lacking. Here, we developed a database named ATtRACT (available athttp://attract.cnic.es) that compiles information on 370 RBPs and 1583 RBP consensus binding motifs, 192 of which are not present in any other database. To populate ATtRACT we (i) extracted and hand-curated experimentally validated data from CISBP-RNA, SpliceAid-F, RBPDB databases, (ii) integrated and updated the unavailable ASD database and (iii) extracted information from Protein-RNA complexes present in Protein Data Bank database through computational analyses. ATtRACT provides also efficient algorithms to search a specific motif and scan one or more RNA sequences at a time. It also allows discoveringde novomotifs enriched in a set of related sequences and compare them with the motifs included in the database.Database URL:http:// attract. cnic. es.

  10. Insect kinin analogs with cis-peptide bond motif 4-aminopyroglutamate: Optimal stereochemistry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The insect kinins are present in a wide variety of insects and function as potent diuretic peptides, though they are subject to rapid degradation by internal peptidases. Insect kinin analogs incorporating stereochemical variants of (2S,4S)-4-aminopyroglutamate (APy), a cis-peptide bond motif, demon...

  11. Platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling and vascular integrity.

    PubMed

    Boulaftali, Yacine; Hess, Paul R; Kahn, Mark L; Bergmeier, Wolfgang

    2014-03-28

    Platelets are well-known for their critical role in hemostasis, that is, the prevention of blood loss at sites of mechanical vessel injury. Inappropriate platelet activation and adhesion, however, can lead to thrombotic complications, such as myocardial infarction and stroke. To fulfill its role in hemostasis, the platelet is equipped with various G protein-coupled receptors that mediate the response to soluble agonists such as thrombin, ADP, and thromboxane A2. In addition to G protein-coupled receptors, platelets express 3 glycoproteins that belong to the family of immunoreceptor tyrosine-based activation motif receptors: Fc receptor γ chain, which is noncovalently associated with the glycoprotein VI collagen receptor, C-type lectin 2, the receptor for podoplanin, and Fc receptor γII A, a low-affinity receptor for immune complexes. Although both genetic and chemical approaches have documented a critical role for platelet G protein-coupled receptors in hemostasis, the contribution of immunoreceptor tyrosine-based activation motif receptors to this process is less defined. Studies performed during the past decade, however, have identified new roles for platelet immunoreceptor tyrosine-based activation motif signaling in vascular integrity in utero and at sites of inflammation. The purpose of this review is to summarize recent findings on how platelet immunoreceptor tyrosine-based activation motif signaling controls vascular integrity, both in the presence and absence of mechanical injury.

  12. The LIM motif defines a specific zinc-binding protein domain.

    PubMed

    Michelsen, J W; Schmeichel, K L; Beckerle, M C; Winge, D R

    1993-05-15

    The cysteine-rich protein (CRP) contains two copies of the LIM sequence motif, CX2CX17HX2CX2CX2CX17-CX2C, that was first identified in the homeodomain proteins Lin-11, Is1-1, and Mec-3. The abundance and spacing of the cysteine residues in the LIM motif are reminiscent of a metal-binding domain. We examined the metal-binding properties of CRP isolated from chicken smooth muscle (cCRP) and from a bacterial expression system and observed that cCRP is a specific Zn-binding metalloprotein. Four Zn(II) ions are maximally bound to cCRP, consistent with the idea that each LIM domain coordinates two metal ions. From spectroscopic studies of Co(II)- and 113Cd(II)-substituted cCRP, we determined that each metal ion is tetrahedrally coordinated with cysteinyl sulfurs dominating the ligand types. One metal site within each LIM motif has tetrathiolate (S4) coordination, the second site may either be S4 or S3N1. The LIM motif represents another example of a specific Zn-binding protein sequence.

  13. Conserved sequence motifs among bacterial, eukaryotic, and archaeal phosphatases that define a new phosphohydrolase superfamily.

    PubMed Central

    Thaller, M. C.; Schippa, S.; Rossolini, G. M.

    1998-01-01

    Members of a new molecular family of bacterial nonspecific acid phosphatases (NSAPs), indicated as class C, were found to share significant sequence similarities to bacterial class B NSAPs and to some plant acid phosphatases, representing the first example of a family of bacterial NSAPs that has a relatively close eukaryotic counterpart. Despite the lack of an overall similarity, conserved sequence motifs were also identified among the above enzyme families (class B and class C bacterial NSAPs, and related plant phosphatases) and several other families of phosphohydrolases, including bacterial phosphoglycolate phosphatases, histidinol-phosphatase domains of the bacterial bifunctional enzymes imidazole-glycerolphosphate dehydratases, and bacterial, eukaryotic, and archaeal phosphoserine phosphatases and threalose-6-phosphatases. These conserved motifs are clustered within two domains, separated by a variable spacer region, according to the pattern [FILMAVT]-D-[ILFRMVY]-D-[GSNDE]-[TV]-[ILVAM]-[AT S VILMC]-X-¿YFWHKR)-X-¿YFWHNQ¿-X( 102,191)-¿KRHNQ¿-G-D-¿FYWHILVMC¿-¿QNH¿-¿FWYGP¿-D -¿PSNQYW¿. The dephosphorylating activity common to all these proteins supports the definition of this phosphatase motif and the inclusion of these enzymes into a superfamily of phosphohydrolases that we propose to indicate as "DDDD" after the presence of the four invariant aspartate residues. Database searches retrieved various hypothetical proteins of unknown function containing this or similar motifs, for which a phosphohydrolase activity could be hypothesized. PMID:9684901

  14. The extended AT-hook is a novel RNA binding motif.

    PubMed

    Filarsky, Michael; Zillner, Karina; Araya, Ingrid; Villar-Garea, Ana; Merkl, Rainer; Längst, Gernot; Németh, Attila

    2015-01-01

    The AT-hook has been defined as a DNA binding peptide motif that contains a glycine-arginine-proline (G-R-P) tripeptide core flanked by basic amino acids. Recent reports documented variations in the sequence of AT-hooks and revealed RNA binding activity of some canonical AT-hooks, suggesting a higher structural and functional variability of this protein domain than previously anticipated. Here we describe the discovery and characterization of the extended AT-hook peptide motif (eAT-hook), in which basic amino acids appear symmetrical mainly at a distance of 12-15 amino acids from the G-R-P core. We identified 80 human and 60 mouse eAT-hook proteins and biochemically characterized the eAT-hooks of Tip5/BAZ2A, PTOV1 and GPBP1. Microscale thermophoresis and electrophoretic mobility shift assays reveal the nucleic acid binding features of this peptide motif, and show that eAT-hooks bind RNA with one order of magnitude higher affinity than DNA. In addition, cellular localization studies suggest a role for the N-terminal eAT-hook of PTOV1 in nucleocytoplasmic shuttling. In summary, our findings classify the eAT-hook as a novel nucleic acid binding motif, which potentially mediates various RNA-dependent cellular processes.

  15. Temporal motifs reveal collaboration patterns in online task-oriented networks

    NASA Astrophysics Data System (ADS)

    Xuan, Qi; Fang, Huiting; Fu, Chenbo; Filkov, Vladimir

    2015-05-01

    Real networks feature layers of interactions and complexity. In them, different types of nodes can interact with each other via a variety of events. Examples of this complexity are task-oriented social networks (TOSNs), where teams of people share tasks towards creating a quality artifact, such as academic research papers or software development in commercial or open source environments. Accomplishing those tasks involves both work, e.g., writing the papers or code, and communication, to discuss and coordinate. Taking into account the different types of activities and how they alternate over time can result in much more precise understanding of the TOSNs behaviors and outcomes. That calls for modeling techniques that can accommodate both node and link heterogeneity as well as temporal change. In this paper, we report on methodology for finding temporal motifs in TOSNs, limited to a system of two people and an artifact. We apply the methods to publicly available data of TOSNs from 31 Open Source Software projects. We find that these temporal motifs are enriched in the observed data. When applied to software development outcome, temporal motifs reveal a distinct dependency between collaboration and communication in the code writing process. Moreover, we show that models based on temporal motifs can be used to more precisely relate both individual developer centrality and team cohesion to programmer productivity than models based on aggregated TOSNs.

  16. Some motifs were important for myostatin transcriptional regulation in sheep (Ovis aries).

    PubMed

    Du, Rong; An, Xiao-Rong; Chen, Yong-Fu; Qin, Jian

    2007-07-31

    Many motifs along the 1.2 kb myostatin promoter (MSTNpro) in sheep have been found by the MatInspecter program in our recent study. To further verify the role of the motifs and better understand the transcriptional regulation mechanism of the myostatin gene in sheep, the reporter gene EGFP (enhanced green fluorescent protein) was selected and the wild-type (W) vector MSTNPro(W)-EGFP or motif-mutational (M) vector MSTNPro(M)-EGFP were constructed. The transcriptional regulation activities were analyzed by detecting the fluorescence strength of EGFP in C2C12 myoblasts transfected with the vectors. The results showed that E-box (E) 3, E4, E5 and E7, particularly E3, E5 and E7, had important effects on the activity of the 1.2 kb sheep myostatin promoter. In addition, we also detected several other important motifs such as MTBF (muscle-specific Mt binding factor), MEF2 (myocyte enhancer factor 2), GRE (glucocorticoid response elements) and PRE (progesterone response elements) along the sheep myostatin promoter by the mutational analysis.

  17. Negative regulation of defence and stress genes by EAR-motif-containing repressors.

    PubMed

    Kazan, Kemal

    2006-03-01

    Although positive control or activation mechanism(s) involved in plant defence- and stress-related gene expression is relatively well studied, little is known about what keeps defensive armoury under control when not needed. Recent reports suggest that transcriptional repression of gene expression by EAR-motif-containing repressor proteins plays a key role in modulating plant defence and stress responses.

  18. Dipeptide frequency/bias analysis identifies conserved sites of nonrandomness shared by cysteine-rich motifs.

    PubMed

    Campion, S R; Ameen, A S; Lai, L; King, J M; Munzenmaier, T N

    2001-08-15

    This report describes the application of a simple computational tool, AAPAIR.TAB, for the systematic analysis of the cysteine-rich EGF, Sushi, and Laminin motif/sequence families at the two-amino acid level. Automated dipeptide frequency/bias analysis detects preferences in the distribution of amino acids in established protein families, by determining which "ordered dipeptides" occur most frequently in comprehensive motif-specific sequence data sets. Graphic display of the dipeptide frequency/bias data revealed family-specific preferences for certain dipeptides, but more importantly detected a shared preference for employment of the ordered dipeptides Gly-Tyr (GY) and Gly-Phe (GF) in all three protein families. The dipeptide Asn-Gly (NG) also exhibited high-frequency and bias in the EGF and Sushi motif families, whereas Asn-Thr (NT) was distinguished in the Laminin family. Evaluation of the distribution of dipeptides identified by frequency/bias analysis subsequently revealed the highly restricted localization of the G(F/Y) and N(G/T) sequence elements at two separate sites of extreme conservation in the consensus sequence of all three sequence families. The similar employment of the high-frequency/bias dipeptides in three distinct protein sequence families was further correlated with the concurrence of these shared molecular determinants at similar positions within the distinctive scaffolds of three structurally divergent, but similarly employed, motif modules.

  19. Structural motifs recurring in different folds recognize the same ligand fragments

    PubMed Central

    Ausiello, Gabriele; Gherardini, Pier Federico; Gatti, Elena; Incani, Ottaviano; Helmer-Citterich, Manuela

    2009-01-01

    Background The structural analysis of protein ligand binding sites can provide information relevant for assigning functions to unknown proteins, to guide the drug discovery process and to infer relations among distant protein folds. Previous approaches to the comparative analysis of binding pockets have usually been focused either on the ligand or the protein component. Even though several useful observations have been made with these approaches they both have limitations. In the former case the analysis is restricted to binding pockets interacting with similar ligands, while in the latter it is difficult to systematically check whether the observed structural similarities have a functional significance. Results Here we propose a novel methodology that takes into account the structure of both the binding pocket and the ligand. We first look for local similarities in a set of binding pockets and then check whether the bound ligands, even if completely different, share a common fragment that can account for the presence of the structural motif. Thanks to this method we can identify structural motifs whose functional significance is explained by the presence of shared features in the interacting ligands. Conclusion The application of this method to a large dataset of binding pockets allows the identification of recurring protein motifs that bind specific ligand fragments, even in the context of molecules with a different overall structure. In addition some of these motifs are present in a high number of evolutionarily unrelated proteins. PMID:19527512

  20. Modelling Liquid Particle Composition In Polar Stratospheric Clouds

    NASA Astrophysics Data System (ADS)

    Lowe, D.; MacKenzie, A. R.

    Polar Stratospheric Clouds (PSCs) are thought to be composed of solid ni- tric acid trihydrate (NAT) particles, water ice particles, or supercooled liquid HNO3/H2SO4/H2O particles under different conditions and depending on the ther- mal history of the air mass. The solid particles are believed to form by the freezing of the liquid particles, the rate of which depends on the composition and size of the liquid particles. Lagrangian-in-radius-space numerical schemes have been used be- fore to study particle composition across the PSC size spectrum, in simple box model runs and in domain-filling Lagrangian studies. However these models were not de- signed to be compatible with global chemistry and transport models (CTMs), which currently model PSCs by assuming equilibrium with the atmosphere.We report here on an adaptation of a continuous (Eulerian-in-radius) distribution scheme, modelling the evolution of liquid PSC particles in non-equilibrium conditions. It uses an effi- cient numerical scheme, designed to be compatible with CTMs. Results from the new scheme have been validated against analytical solutions, and corroborate the compo- sition gradients across the size distribution under rapid cooling conditions that were reported in earlier studies.

  1. An SOS Regulon under Control of a Noncanonical LexA-Binding Motif in the Betaproteobacteria

    PubMed Central

    Sanchez-Alberola, Neus; Campoy, Susana; Emerson, David; Barbé, Jordi

    2015-01-01

    ABSTRACT The SOS response is a transcriptional regulatory network governed by the LexA repressor that activates in response to DNA damage. In the Betaproteobacteria, LexA is known to target a palindromic sequence with the consensus sequence CTGT-N8-ACAG. We report the characterization of a LexA regulon in the iron-oxidizing betaproteobacterium Sideroxydans lithotrophicus. In silico and in vitro analyses show that LexA targets six genes by recognizing a binding motif with the consensus sequence GAACGaaCGTTC, which is strongly reminiscent of the Bacillus subtilis LexA-binding motif. We confirm that the closely related Gallionella capsiferriformans shares the same LexA-binding motif, and in silico analyses indicate that this motif is also conserved in the Nitrosomonadales and the Methylophilales. Phylogenetic analysis of LexA and the alpha subunit of DNA polymerase III (DnaE) reveal that the organisms harboring this noncanonical LexA form a compact taxonomic cluster within the Betaproteobacteria. However, their lexA gene is unrelated to the standard Betaproteobacteria lexA, and there is evidence of its spread through lateral gene transfer. In contrast to other reported cases of noncanonical LexA-binding motifs, the regulon of S. lithotrophicus is comparable in size and function to that of many other Betaproteobacteria, suggesting that a convergent SOS regulon has reevolved under the control of a new LexA protein. Analysis of the DNA-binding domain of S. lithotrophicus LexA reveals little sequence similarity with that of other LexA proteins targeting similar binding motifs, suggesting that network structure may limit site evolution or that structural constrains make the B. subtilis-type motif an optimal interface for multiple LexA sequences. IMPORTANCE Understanding the evolution of transcriptional systems enables us to address important questions in microbiology, such as the emergence and transfer potential of different regulatory systems to regulate virulence or

  2. SA-Mot: a web server for the identification of motifs of interest extracted from protein loops.

    PubMed

    Regad, Leslie; Saladin, Adrien; Maupetit, Julien; Geneix, Colette; Camproux, Anne-Claude

    2011-07-01

    The detection of functional motifs is an important step for the determination of protein functions. We present here a new web server SA-Mot (Structural Alphabet Motif) for the extraction and location of structural motifs of interest from protein loops. Contrary to other methods, SA-Mot does not focus only on functional motifs, but it extracts recurrent and conserved structural motifs involved in structural redundancy of loops. SA-Mot uses the structural word notion to extract all structural motifs from uni-dimensional sequences corresponding to loop structures. Then, SA-Mot provides a description of these structural motifs using statistics computed in the loop data set and in SCOP superfamily, sequence and structural parameters. SA-Mot results correspond to an interactive table listing all structural motifs extracted from a target structure and their associated descriptors. Using this information, the users can easily locate loop regions that are important for the protein folding and function. The SA-Mot web server is available at http://sa-mot.mti.univ-paris-diderot.fr.

  3. GRISOTTO: A greedy approach to improve combinatorial algorithms for motif discovery with prior knowledge

    PubMed Central

    2011-01-01

    Background Position-specific priors (PSP) have been used with success to boost EM and Gibbs sampler-based motif discovery algorithms. PSP information has been computed from different sources, including orthologous conservation, DNA duplex stability, and nucleosome positioning. The use of prior information has not yet been used in the context of combinatorial algorithms. Moreover, priors have been used only independently, and the gain of combining priors from different sources has not yet been studied. Results We extend RISOTTO, a combinatorial algorithm for motif discovery, by post-processing its output with a greedy procedure that uses prior information. PSP's from different sources are combined into a scoring criterion that guides the greedy search procedure. The resulting method, called GRISOTTO, was evaluated over 156 yeast TF ChIP-chip sequence-sets commonly used to benchmark prior-based motif discovery algorithms. Results show that GRISOTTO is at least as accurate as other twelve state-of-the-art approaches for the same task, even without combining priors. Furthermore, by considering combined priors, GRISOTTO is considerably more accurate than the state-of-the-art approaches for the same task. We also show that PSP's improve GRISOTTO ability to retrieve motifs from mouse ChiP-seq data, indicating that the proposed algorithm can be applied to data from a different technology and for a higher eukaryote. Conclusions The conclusions of this work are twofold. First, post-processing the output of combinatorial algorithms by incorporating prior information leads to a very efficient and effective motif discovery method. Second, combining priors from different sources is even more beneficial than considering them separately. PMID:21513505

  4. Unique motifs identify PIG-A proteins from glycosyltransferases of the GT4 family

    PubMed Central

    2008-01-01

    Background The first step of GPI anchor biosynthesis is catalyzed by PIG-A, an enzyme that transfers N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol. This protein is present in all eukaryotic organisms ranging from protozoa to higher mammals, as part of a larger complex of five to six 'accessory' proteins whose individual roles in the glycosyltransferase reaction are as yet unclear. The PIG-A gene has been shown to be an essential gene in various eukaryotes. In humans, mutations in the protein have been associated with paroxysomal noctural hemoglobuinuria. The corresponding PIG-A gene has also been recently identified in the genome of many archaeabacteria although genes of the accessory proteins have not been discovered in them. The present study explores the evolution of PIG-A and the phylogenetic relationship between this protein and other glycosyltransferases. Results In this paper we show that out of the twelve conserved motifs identified by us eleven are exclusively present in PIG-A and, therefore, can be used as markers to identify PIG-A from newly sequenced genomes. Three of these motifs are absent in the primitive eukaryote, G. lamblia. Sequence analyses show that seven of these conserved motifs are present in prokaryote and archaeal counterparts in rudimentary forms and can be used to differentiate PIG-A proteins from glycosyltransferases. Using partial least square regression analysis and data involving presence or absence of motifs in a range of PIG-A and glycosyltransferases we show that (i) PIG-A may have evolved from prokaryotic glycosyltransferases and lipopolysaccharide synthases, members of the GT4 family of glycosyltransferases and (ii) it is possible to uniquely classify PIG-A proteins versus glycosyltransferases. Conclusion Besides identifying unique motifs and showing that PIG-A protein from G. lamblia and some putative PIG-A proteins from archaebacteria are evolutionarily closer to glycosyltransferases, these studies

  5. The DRF motif of CXCR6 as chemokine receptor adaptation to adhesion

    PubMed Central

    Koenen, Andrea; Babendreyer, Aaron; Schumacher, Julian; Pasqualon, Tobias; Schwarz, Nicole; Seifert, Anke; Deupi, Xavier

    2017-01-01

    The CXC-chemokine receptor 6 (CXCR6) is a class A GTP-binding protein-coupled receptor (GPCRs) that mediates adhesion of leukocytes by interacting with the transmembrane cell surface-expressed chemokine ligand 16 (CXCL16), and also regulates leukocyte migration by interacting with the soluble shed variant of CXCL16. In contrast to virtually all other chemokine receptors with chemotactic activity, CXCR6 carries a DRF motif instead of the typical DRY motif as a key element in receptor activation and G protein coupling. In this work, modeling analyses revealed that the phenylalanine F3.51 in CXCR6 might have impact on intramolecular interactions including hydrogen bonds by this possibly changing receptor function. Initial investigations with embryonic kidney HEK293 cells and further studies with monocytic THP-1 cells showed that mutation of DRF into DRY does not influence ligand binding, receptor internalization, receptor recycling, and protein kinase B (AKT) signaling. Adhesion was slightly decreased in a time-dependent manner. However, CXCL16-induced calcium signaling and migration were increased. Vice versa, when the DRY motif of the related receptor CX3CR1 was mutated into DRF the migratory response towards CX3CL1 was diminished, indicating that the presence of a DRF motif generally impairs chemotaxis in chemokine receptors. Transmembrane and soluble CXCL16 play divergent roles in homeostasis, inflammation, and cancer, which can be beneficial or detrimental. Therefore, the DRF motif of CXCR6 may display a receptor adaptation allowing adhesion and cell retention by transmembrane CXCL16 but reducing the chemotactic response to soluble CXCL16. This adaptation may avoid permanent or uncontrolled recruitment of inflammatory cells as well as cancer metastasis. PMID:28267793

  6. DISCOVER: a feature-based discriminative method for motif search in complex genomes

    PubMed Central

    Fu, Wenjie; Ray, Pradipta; Xing, Eric P.

    2009-01-01

    Motivation: Identifying transcription factor binding sites (TFBSs) encoding complex regulatory signals in metazoan genomes remains a challenging problem in computational genomics. Due to degeneracy of nucleotide content among binding site instances or motifs, and intricate ‘grammatical organization’ of motifs within cis-regulatory modules (CRMs), extant pattern matching-based in silico motif search methods often suffer from impractically high false positive rates, especially in the context of analyzing large genomic datasets, and noisy position weight matrices which characterize binding sites. Here, we try to address this problem by using a framework to maximally utilize the information content of the genomic DNA in the region of query, taking cues from values of various biologically meaningful genetic and epigenetic factors in the query region such as clade-specific evolutionary parameters, presence/absence of nearby coding regions, etc. We present a new method for TFBS prediction in metazoan genomes that utilizes both the CRM architecture of sequences and a variety of features of individual motifs. Our proposed approach is based on a discriminative probabilistic model known as conditional random fields that explicitly optimizes the predictive probability of motif presence in large sequences, based on the joint effect of all such features. Results: This model overcomes weaknesses in earlier methods based on less effective statistical formalisms that are sensitive to spurious signals in the data. We evaluate our method on both simulated CRMs and real Drosophila sequences in comparison with a wide spectrum of existing models, and outperform the state of the art by 22% in F1 score. Availability and Implementation: The code is publicly available at http://www.sailing.cs.cmu.edu/discover.html. Contact: epxing@cs.cmu.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19478006

  7. Dry Sliding Wear Behaviour of Flyash Reinforced ZA-27 Alloy Based Metal Matrix Composites

    NASA Astrophysics Data System (ADS)

    Sharma, S. C.; Krishna, M.; Bhattacharyya, D.

    In the present investigation, an attempt has been made to evaluate the wear rate of ZA-27 alloy composites reinforced with fly ash particles from 1 to 3 wt% in steps of 1 wt%. The compo-casting method has been used to fabricate the composites using Raichur fly ash of average size 3-5 microns. The wear specimens are tested under dry conditions using a pin-on-disc sliding wear testing machine with wear loads of 20-120 N in steps of 20 N, and the sliding distances in the range of 0.5 km to 2.5 km. The results indicate that the wear rate of the composites is less than that of the matrix alloy and it further decreases with the increase in fly ash content. However, the material loss in terms of wear rate and wear volume increases with the increase in load and sliding distance, both in the cases of composites and the matrix alloy. An increase in the applied load increases the wear severity by changing the wear mechanism from abrasion to particle-cracking induced delamination wear. It is found that with the increase in fly ash content, the wear resistance increases monotonically. The observations have been explained using scanning electron microscope (SEM) analysis of the worn surfaces of the composites.

  8. Analysis of immunoreceptor tyrosine-based activation motif (ITAM) binding to ZAP-70 by surface plasmon resonance.

    PubMed

    Vély, F; Nunès, J A; Malissen, B; Hedgecock, C J

    1997-11-01

    The signaling function of the T cell antigen receptor (TCR) is mediated via CD3 polypeptides, the cytoplasmic sequences of which bear conserved immunoreceptor tyrosine-based activation motifs (ITAM). ITAM are defined by two YxxL/I sequences separated by a six-eight amino acid long spacer. Upon antigen recognition, ITAM become phosphorylated on both tyrosine residues, creating a high affinity binding site for the tandem SH2 domains found in the protein tyrosine kinase ZAP-70. Using surface plasmon resonance, we further dissected the sequences required for the binding of ZAP-70 to each TCR-associated ITAM. First, we generated protein tyrosine phosphatase-resistant ITAM peptide analogs, in which difluorophosphonomethyl phenylalanyl (F2p) replaced both phosphotyrosines, and showed that those protein tyrosine phosphatase-resistant analogs bind ZAP-70 with high affinity, establishing a rational strategy for the design of novel pharmacological tools capable of interfering with TCR signaling function. Second, we substituted the five amino acids separating the two YxxL/I sequences of the CD3 zeta 1 ITAM with a non-peptidic linker made up of gamma-amino butyric acid units and demonstrated that the length of this intervening sequence rather than its chemical composition is essential for high affinity binding of phosphorylated ITAM to the ZAP-70 SH2 domains.

  9. Isosteric and nonisosteric base pairs in RNA motifs: molecular dynamics and bioinformatics study of the sarcin-ricin internal loop.

    PubMed

    Havrila, Marek; Réblová, Kamila; Zirbel, Craig L; Leontis, Neocles B; Šponer, Jiří

    2013-11-21

    The sarcin-ricin RNA motif (SR motif) is one of the most prominent recurrent RNA building blocks that occurs in many different RNA contexts and folds autonomously, that is, in a context-independent manner. In this study, we combined bioinformatics analysis with explicit-solvent molecular dynamics (MD) simulations to better understand the relation between the RNA sequence and the evolutionary patterns of the SR motif. A SHAPE probing experiment was also performed to confirm the fidelity of the MD simulations. We identified 57 instances of the SR motif in a nonredundant subset of the RNA X-ray structure database and analyzed their base pairing, base-phosphate, and backbone-backbone interactions. We extracted sequences aligned to these instances from large rRNA alignments to determine the frequency of occurrence for different sequence variants. We then used a simple scoring scheme based on isostericity to suggest 10 sequence variants with a highly variable expected degree of compatibility with the SR motif 3D structure. We carried out MD simulations of SR motifs with these base substitutions. Nonisosteric base substitutions led to unstable structures, but so did isosteric substitutions which were unable to make key base-phosphate interactions. The MD technique explains why some potentially isosteric SR motifs are not realized during evolution. We also found that the inability to form stable cWW geometry is an important factor in the case of the first base pair of the flexible region of the SR motif. A comparison of structural, bioinformatics, SHAPE probing, and MD simulation data reveals that explicit solvent MD simulations neatly reflect the viability of different sequence variants of the SR motif. Thus, MD simulations can efficiently complement bioinformatics tools in studies of conservation patterns of RNA motifs and provide atomistic insight into the role of their different signature interactions.

  10. SLiMScape 3.x: a Cytoscape 3 app for discovery of Short Linear Motifs in protein interaction networks.

    PubMed

    Olorin, Emily; O'Brien, Kevin T; Palopoli, Nicolas; Pérez-Bercoff, Åsa; Shields, Denis C; Edwards, Richard J

    2015-01-01

    Short linear motifs (SLiMs) are small protein sequence patterns that mediate a large number of critical protein-protein interactions, involved in processes such as complex formation, signal transduction, localisation and stabilisation. SLiMs show rapid evolutionary dynamics and are frequently the targets of molecular mimicry by pathogens. Identifying enriched sequence patterns due to convergent evolution in non-homologous proteins has proven to be a successful strategy for computational SLiM prediction. Tools of the SLiMSuite package use this strategy, using a statistical model to identify SLiM enrichment based on the evolutionary relationships, amino acid composition and predicted disorder of the input proteins. The quality of input data is critical for successful SLiM prediction. Cytoscape provides a user-friendly, interactive environment to explore interaction networks and select proteins based on common features, such as shared interaction partners. SLiMScape embeds tools of the SLiMSuite package for de novo SLiM discovery (SLiMFinder and QSLiMFinder) and identifying occurrences/enrichment of known SLiMs (SLiMProb) within this interactive framework. SLiMScape makes it easier to (1) generate high quality hypothesis-driven datasets for these tools, and (2) visualise predicted SLiM occurrences within the context of the network. To generate new predictions, users can select nodes from a protein network or provide a set of Uniprot identifiers. SLiMProb also requires additional query motif input. Jobs are then run remotely on the SLiMSuite server ( http://rest.slimsuite.unsw.edu.au) for subsequent retrieval and visualisation. SLiMScape can also be used to retrieve and visualise results from jobs run directly on the server. SLiMScape and SLiMSuite are open source and freely available via GitHub under GNU licenses.

  11. Effector prediction in host-pathogen interaction based on a Markov model of a ubiquitous EPIYA motif

    PubMed Central

    2010-01-01

    Background Effector secretion is a common strategy of pathogen in mediating host-pathogen interaction. Eight EPIYA-motif containing effectors have recently been discovered in six pathogens. Once these effectors enter host cells through type III/IV secretion systems (T3SS/T4SS), tyrosine in the EPIYA motif is phosphorylated, which triggers effectors binding other proteins to manipulate host-cell functions. The objectives of this study are to evaluate the distribution pattern of EPIYA motif in broad biological species, to predict potential effectors with EPIYA motif, and to suggest roles and biological functions of potential effectors in host-pathogen interactions. Results A hidden Markov model (HMM) of five amino acids was built for the EPIYA-motif based on the eight known effectors. Using this HMM to search the non-redundant protein database containing 9,216,047 sequences, we obtained 107,231 sequences with at least one EPIYA motif occurrence and 3115 sequences with multiple repeats of the EPIYA motif. Although the EPIYA motif exists among broad species, it is significantly over-represented in some particular groups of species. For those proteins containing at least four copies of EPIYA motif, most of them are from intracellular bacteria, extracellular bacteria with T3SS or T4SS or intracellular protozoan parasites. By combining the EPIYA motif and the adjacent SH2 binding motifs (KK, R4, Tarp and Tir), we built HMMs of nine amino acids and predicted many potential effectors in bacteria and protista by the HMMs. Some potential effectors for pathogens (such as Lawsonia intracellularis, Plasmodium falciparum and Leishmania major) are suggested. Conclusions Our study indicates that the EPIYA motif may be a ubiquitous functional site for effectors that play an important pathogenicity role in mediating host-pathogen interactions. We suggest that some intracellular protozoan parasites could secrete EPIYA-motif containing effectors through secretion systems similar to the

  12. Microglial activatory (immunoreceptor tyrosine-based activation motif)- and inhibitory (immunoreceptor tyrosine-based inhibition motif)-signaling receptors for recognition of the neuronal glycocalyx.

    PubMed

    Linnartz, Bettina; Neumann, Harald

    2013-01-01

    Microglia sense intact or lesioned cells of the central nervous system (CNS) and respond accordingly. To fulfill this task, microglia express a whole set of recognition receptors. Fc receptors and DAP12 (TYROBP)-associated receptors such as microglial triggering receptor expressed on myeloid cells-2 (TREM2) and the complement receptor-3 (CR3, CD11b/CD18) trigger the immunoreceptor tyrosine-based activation motif (ITAM)-signaling cascade, resulting in microglial activation, migration, and phagocytosis. Those receptors are counter-regulated by immunoreceptor tyrosine-based inhibition motif (ITIM)-signaling receptors, such as sialic acid-binding immunoglobulin superfamily lectins (Siglecs). Siglecs recognize the sialic acid cap of healthy neurons thus leading to an ITIM signaling that turns down microglial immune responses and phagocytosis. In contrast, desialylated neuronal processes are phagocytosed by microglial CR3 signaling via an adaptor protein containing an ITAM. Thus, the aberrant terminal glycosylation of neuronal surface glycoproteins and glycolipids could serve as a flag for microglia, which display a multitude of diverse carbohydrate-binding receptors that monitor the neuronal physical condition and respond via their ITIM- or ITAM-signaling cascade accordingly.

  13. Composition-dependent stability of the medium-range order responsible for metallic glass formation

    DOE PAGES

    Zhang, Feng; Ji, Min; Fang, Xiao-Wei; ...

    2014-09-18

    The competition between the characteristic medium-range order corresponding to amorphous alloys and that in ordered crystalline phases is central to phase selection and morphology evolution under various processing conditions. We examine the stability of a model glass system, Cu–Zr, by comparing the energetics of various medium-range structural motifs over a wide range of compositions using first-principles calculations. Furthermore, we focus specifically on motifs that represent possible building blocks for competing glassy and crystalline phases, and we employ a genetic algorithm to efficiently identify the energetically favored decorations of each motif for specific compositions. These results show that a Bergman-type motifmore » with crystallization-resisting icosahedral symmetry is energetically most favorable in the composition range 0.63 < xCu < 0.68, and is the underlying motif for one of the three optimal glass-forming ranges observed experimentally for this binary system (Li et al., 2008). This work establishes an energy-based methodology to evaluate specific medium-range structural motifs which compete with stable crystalline nuclei in deeply undercooled liquids.« less

  14. Sequence-motif Detection of NAD(P)-binding Proteins: Discovery of a Unique Antibacterial Drug Target

    NASA Astrophysics Data System (ADS)

    Hua, Yun Hao; Wu, Chih Yuan; Sargsyan, Karen; Lim, Carmay

    2014-09-01

    Many enzymes use nicotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate (NAD(P)) as essential coenzymes. These enzymes often do not share significant sequence identity and cannot be easily detected by sequence homology. Previously, we determined all distinct locally conserved pyrophosphate-binding structures (3d motifs) from NAD(P)-bound protein structures, from which 1d sequence motifs were derived. Here, we aim to establish the precision of these 3d and 1d motifs to annotate NAD(P)-binding proteins. We show that the pyrophosphate-binding 3d motifs are characteristic of NAD(P)-binding proteins, as they are rarely found in nonNAD(P)-binding proteins. Furthermore, several 1d motifs could distinguish between proteins that bind only NAD and those that bind only NADP. They could also distinguish between NAD(P)-binding proteins from nonNAD(P)-binding ones. Interestingly, one of the pyrophosphate-binding 3d and corresponding 1d motifs was found only in enoyl-acyl carrier protein reductases, which are enzymes essential for bacterial fatty acid biosynthesis. This unique 3d motif serves as an attractive novel drug target, as it is conserved across many bacterial species and is not found in human proteins.

  15. A comprehensive classification and nomenclature of carboxyl–carboxyl(ate) supramolecular motifs and related catemers: implications for biomolecular systems

    PubMed Central

    D’Ascenzo, Luigi; Auffinger, Pascal

    2015-01-01

    Carboxyl and carboxylate groups form important supramolecular motifs (synthons). Besides carboxyl cyclic dimers, carboxyl and carboxylate groups can associate through a single hydrogen bond. Carboxylic groups can further form polymeric-like catemer chains within crystals. To date, no exhaustive classification of these motifs has been established. In this work, 17 association types were identified (13 carboxyl–carboxyl and 4 carboxyl–carboxylate motifs) by taking into account the syn and anti carboxyl conformers, as well as the syn and anti lone pairs of the O atoms. From these data, a simple rule was derived stating that only eight distinct catemer motifs involving repetitive combinations of syn and anti carboxyl groups can be formed. Examples extracted from the Cambridge Structural Database (CSD) for all identified dimers and catemers are presented, as well as statistical data related to their occurrence and conformational preferences. The inter-carboxyl(ate) and carboxyl(ate)–water hydrogen-bond properties are described, stressing the occurrence of very short (strong) hydrogen bonds. The precise characterization and classification of these supramolecular motifs should be of interest in crystal engineering, pharmaceutical and also biomolecular sciences, where similar motifs occur in the form of pairs of Asp/Glu amino acids or motifs involving ligands bearing carboxyl(ate) groups. Hence, we present data emphasizing how the analysis of hydrogen-containing small molecules of high resolution can help understand structural aspects of larger and more complex biomolecular systems of lower resolution. PMID:25827369

  16. A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities.

    PubMed

    Martínez-Bonet, Marta; Palladino, Claudia; Briz, Veronica; Rudolph, Jochen M; Fackler, Oliver T; Relloso, Miguel; Muñoz-Fernandez, Maria Angeles; Madrid, Ricardo

    2015-01-01

    To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121-137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection.

  17. A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities

    PubMed Central

    Martínez-Bonet, Marta; Palladino, Claudia; Briz, Veronica; Rudolph, Jochen M.; Fackler, Oliver T.; Relloso, Miguel; Muñoz-Fernandez, Maria Angeles; Madrid, Ricardo

    2015-01-01

    To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121–137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection. PMID:26700863

  18. EAR motif-mediated transcriptional repression in plants: an underlying mechanism for epigenetic regulation of gene expression.

    PubMed

    Kagale, Sateesh; Rozwadowski, Kevin

    2011-02-01

    Ethylene-responsive element binding factor-associated Amphiphilic Repression (EAR) motif-mediated transcriptional repression is emerging as one of the principal mechanisms of plant gene regulation. The EAR motif, defined by the consensus sequence patterns of either LxLxL or DLNxxP, is the most predominant form of transcriptional repression motif so far identified in plants. Additionally, this active repression motif is highly conserved in transcriptional regulators known to function as negative regulators in a broad range of developmental and physiological processes across evolutionarily diverse plant species. Recent discoveries of co-repressors interacting with EAR motifs, such as TOPLESS (TPL) and AtSAP18, have begun to unravel the mechanisms of EAR motif-mediated repression. The demonstration of genetic interaction between mutants of TPL and AtHDA19, co-complex formation between TPL-related 1 (TPR1) and AtHDA19, as well as direct physical interaction between AtSAP18 and AtHDA19 support a model where EAR repressors, via recruitment of chromatin remodeling factors, facilitate epigenetic regulation of gene expression. Here, we discuss the biological significance of EAR-mediated gene regulation in the broader context of plant biology and present literature evidence in support of a model for EAR motif-mediated repression via the recruitment and action of chromatin modifiers. Additionally, we discuss the possible influences of phosphorylation and ubiquitination on the function and turnover of EAR repressors.

  19. Computational Prediction of Phylogenetically Conserved Sequence Motifs for Five Different Candidate Genes in Type II Diabetic Nephropathy

    PubMed Central

    Sindhu, T; Rajamanikandan, S; Srinivasan, P

    2012-01-01

    Background: Computational identification of phylogenetic motifs helps to understand the knowledge about known functional features that includes catalytic site, substrate binding epitopes, and protein-protein interfaces. Furthermore, they are strongly conserved among orthologs, indicating their evolutionary importance. The study aimed to analyze five candidate genes involved in type II diabetic nephropathy and to predict phylogenetic motifs from their corresponding orthologous protein sequences. Methods: AKR1B1, APOE, ENPP1, ELMO1 and IGFBP1 are the genes that have been identified as an important target for type II diabetic nephropathy through experimental studies. Their corresponding protein sequences, structures, orthologous sequences were retrieved from UniprotKB, PDB, and PHOG database respectively. Multiple sequence alignments were constructed using ClustalW and phylogenetic motifs were identified using MINER. The occurrence of amino acids in the obtained phylogenetic motifs was generated using WebLogo and false positive expectations were calculated against phylogenetic similarity. Results: In total, 17 phylogenetic motifs were identified from the five proteins and the residues such as glycine, leucine, tryptophan, aspartic acid were found in appreciable frequency whereas arginine identified in all the predicted PMs. The result implies that these residues can be important to the functional and structural role of the proteins and calculated false positive expectations implies that they were generally conserved in traditional sense. Conclusion: The prediction of phylogenetic motifs is an accurate method for detecting functionally important conserved residues. The conserved motifs can be used as a potential drug target for type II diabetic nephropathy. PMID:23113206

  20. Investigating the mechanism of the assembly of FGF1-binding heparan sulfate motifs

    PubMed Central

    Nguyen, Thao Kim Nu; Raman, Karthik; Trana, Vy My; Kuberan, Balagurunathan

    2011-01-01

    Heparan sulfate (HS) chains play crucial biological roles by binding to various signaling molecules including fibroblast growth factors (FGFs). Distinct sulfation patterns of HS chains are required for their binding to FGFs/FGF receptors (FGFRs). These sulfation patterns are putatively regulated by biosynthetic enzyme complexes, called GAGOSOMES, in the Golgi. While the structural requirements of HS-FGF interactions have been described previously, it is still unclear how the FGF-binding motif is assembled in vivo. In this study, we generated HS structures using biosynthetic enzymes in a sequential or concurrent manner to elucidate the potential mechanism by which the FGF1-binding HS motif is assembled. Our results indicate that the HS chains form ternary complexes with FGF1/FGFR when enzymes carry out modifications in a specific manner. PMID:21803043

  1. Native characterization of nucleic acid motif thermodynamics via non-covalent catalysis

    PubMed Central

    Wang, Chunyan; Bae, Jin H.; Zhang, David Yu

    2016-01-01

    DNA hybridization thermodynamics is critical for accurate design of oligonucleotides for biotechnology and nanotechnology applications, but parameters currently in use are inaccurately extrapolated based on limited quantitative understanding of thermal behaviours. Here, we present a method to measure the ΔG° of DNA motifs at temperatures and buffer conditions of interest, with significantly better accuracy (6- to 14-fold lower s.e.) than prior methods. The equilibrium constant of a reaction with thermodynamics closely approximating that of a desired motif is numerically calculated from directly observed reactant and product equilibrium concentrations; a DNA catalyst is designed to accelerate equilibration. We measured the ΔG° of terminal fluorophores, single-nucleotide dangles and multinucleotide dangles, in temperatures ranging from 10 to 45 °C. PMID:26782977

  2. Regulation of α2B-Adrenerigc Receptor Export Trafficking by Specific Motifs.

    PubMed

    Wu, Guangyu; Davis, Jason E; Zhang, Maoxiang

    2015-01-01

    Intracellular trafficking and precise targeting to specific locations of G protein-coupled receptors (GPCRs) control the physiological functions of the receptors. Compared to the extensive efforts dedicated to understanding the events involved in the endocytic and recycling pathways, the molecular mechanisms underlying the transport of the GPCR superfamily from the endoplasmic reticulum (ER) through the Golgi to the plasma membrane are relatively less well defined. Over the past years, we have used α(2B)-adrenergic receptor (α(2B)-AR) as a model to define the factors that control GPCR export trafficking. In this chapter, we will review specific motifs identified to mediate the export of nascent α(2B)-AR from the ER and the Golgi and discuss the possible underlying mechanisms. As these motifs are highly conserved among GPCRs, they may provide common mechanisms for export trafficking of these receptors.

  3. Super-transient scaling in time-delay autonomous Boolean network motifs

    NASA Astrophysics Data System (ADS)

    D'Huys, Otti; Lohmann, Johannes; Haynes, Nicholas D.; Gauthier, Daniel J.

    2016-09-01

    Autonomous Boolean networks are commonly used to model the dynamics of gene regulatory networks and allow for the prediction of stable dynamical attractors. However, most models do not account for time delays along the network links and noise, which are crucial features of real biological systems. Concentrating on two paradigmatic motifs, the toggle switch and the repressilator, we develop an experimental testbed that explicitly includes both inter-node time delays and noise using digital logic elements on field-programmable gate arrays. We observe transients that last millions to billions of characteristic time scales and scale exponentially with the amount of time delays between nodes, a phenomenon known as super-transient scaling. We develop a hybrid model that includes time delays along network links and allows for stochastic variation in the delays. Using this model, we explain the observed super-transient scaling of both motifs and recreate the experimentally measured transient distributions.

  4. Pyrene functionalized molecular beacon with pH-sensitive i-motif in a loop.

    PubMed

    Dembska, Anna; Juskowiak, Bernard

    2015-01-01

    In this work, we present a spectral characterization of pH-sensitive system, which combines the i-motif properties with the spatially sensitive fluorescence signal of pyrene molecules attached to hairpin ends. The excimer production (fluorescence max. ∼480 nm) by pyrene labels at the ends of the molecular beacon is driven by pH-dependent i-motif formation in the loop. To illustrate the performance and reversible work of our systems, we performed the experiments with repeatedly pH cycling between pH values of 7.5±0.3 and 6.5±0.3. The sensor gives analytical response in excimer-monomer switching mode in narrow pH range (1.5 pH units) and exhibits high pH resolution (0.1 pH unit).

  5. Quasiracemate Crystal Structures of Magainin 2 Derivatives Support the Functional Significance of the Phenylalanine Zipper Motif.

    PubMed

    Hayouka, Zvi; Thomas, Nicole C; Mortenson, David E; Satyshur, Kenneth A; Weisblum, Bernard; Forest, Katrina T; Gellman, Samuel H

    2015-09-23

    Quasiracemic crystallography has been used to explore the significance of homochiral and heterochiral associations in a set of host-defense peptide derivatives. The previously reported racemic crystal structure of a magainin 2 derivative displayed a homochiral antiparallel dimer association featuring a "phenylalanine zipper" notable for the dual roles of phenylalanines in mediating dimerization and formation of an exposed hydrophobic swath. This motif is seen as well in two new quasiracemate crystals that contain the d form of the magainin 2 derivative along with an l-peptide in which one Ala has been replaced by a β-amino acid residue. This structural trend supports the hypothesis that the Phe zipper motif has functional significance.

  6. The nitrogen responsive transcriptome in potato (Solanum tuberosum L.) reveals significant gene regulatory motifs

    PubMed Central

    Gálvez, José Héctor; Tai, Helen H.; Lagüe, Martin; Zebarth, Bernie J.; Strömvik, Martina V.

    2016-01-01

    Nitrogen (N) is the most important nutrient for the growth of potato (Solanum tuberosum L.). Foliar gene expression in potato plants with and without N supplementation at 180 kg N ha−1 was compared at mid-season. Genes with consistent differences in foliar expression due to N supplementation over three cultivars and two developmental time points were examined. In total, thirty genes were found to be over-expressed and nine genes were found to be under-expressed with supplemented N. Functional relationships between over-expressed genes were found. The main metabolic pathway represented among differentially expressed genes was amino acid metabolism. The 1000 bp upstream flanking regions of the differentially expressed genes were analysed and nine overrepresented motifs were found using three motif discovery algorithms (Seeder, Weeder and MEME). These results point to coordinated gene regulation at the transcriptional level controlling steady state potato responses to N sufficiency. PMID:27193058

  7. Discovery of widespread GTP-binding motifs in genomic DNA and RNA.

    PubMed

    Curtis, Edward A; Liu, David R

    2013-04-18

    Biological RNAs that bind small molecules have been implicated in a variety of regulatory and catalytic processes. Inspired by these examples, we used in vitro selection to search a pool of genome-encoded RNA fragments for naturally occurring GTP aptamers. Several aptamer classes were identified, including one (the "G motif") with a G-quadruplex structure. Further analysis revealed that most RNA and DNA G-quadruplexes bind GTP. The G motif is abundant in eukaryotes, and the human genome contains ~75,000 examples with dissociation constants comparable to the GTP concentration of a eukaryotic cell (~300 μM). G-quadruplexes play roles in diverse cellular processes, and our findings raise the possibility that GTP may play a role in the function of these elements. Consistent with this possibility, the sequence requirements of several classes of regulatory G-quadruplexes parallel those of GTP binding.

  8. A Common Structural Motif in the Binding of Virulence Factors to Bacterial Secretion Chaperones

    SciTech Connect

    Lilic,M.; Vujanac, M.; Stebbins, C.

    2006-01-01

    Salmonella invasion protein A (SipA) is translocated into host cells by a type III secretion system (T3SS) and comprises two regions: one domain binds its cognate type III secretion chaperone, InvB, in the bacterium to facilitate translocation, while a second domain functions in the host cell, contributing to bacterial uptake by polymerizing actin. We present here the crystal structures of the SipA chaperone binding domain (CBD) alone and in complex with InvB. The SipA CBD is found to consist of a nonglobular polypeptide as well as a large globular domain, both of which are necessary for binding to InvB. We also identify a structural motif that may direct virulence factors to their cognate chaperones in a diverse range of pathogenic bacteria. Disruption of this structural motif leads to a destabilization of several chaperone-substrate complexes from different species, as well as an impairment of secretion in Salmonella.

  9. Stabilizing Motifs in Autonomous Boolean Networks and the Yeast Cell Cycle Oscillator

    NASA Astrophysics Data System (ADS)

    Sevim, Volkan; Gong, Xinwei; Socolar, Joshua

    2009-03-01

    Synchronously updated Boolean networks are widely used to model gene regulation. Some properties of these model networks are known to be artifacts of the clocking in the update scheme. Autonomous updating is a less artificial scheme that allows one to introduce small timing perturbations and study stability of the attractors. We argue that the stabilization of a limit cycle in an autonomous Boolean network requires a combination of motifs such as feed-forward loops and auto-repressive links that can correct small fluctuations in the timing of switching events. A recently published model of the transcriptional cell-cycle oscillator in yeast contains the motifs necessary for stability under autonomous updating [1]. [1] D. A. Orlando, et al. Nature (London), 4530 (7197):0 944--947, 2008.

  10. Crystallization and Preliminary X-ray Diffraction Analysis of motif N from Saccharomyces cerevisiae Dbf4

    SciTech Connect

    Matthews, L.; Duong, A; Prasad, A; Duncker, B; Guarne, A

    2009-01-01

    The Cdc7-Dbf4 complex plays an instrumental role in the initiation of DNA replication and is a target of replication-checkpoint responses in Saccharomyces cerevisiae. Cdc7 is a conserved serine/threonine kinase whose activity depends on association with its regulatory subunit, Dbf4. A conserved sequence near the N-terminus of Dbf4 (motif N) is necessary for the interaction of Cdc7-Dbf4 with the checkpoint kinase Rad53. To understand the role of the Cdc7-Dbf4 complex in checkpoint responses, a fragment of Saccharomyces cerevisiae Dbf4 encompassing motif N was isolated, overproduced and crystallized. A complete native data set was collected at 100 K from crystals that diffracted X-rays to 2.75 {angstrom} resolution and structure determination is currently under way.

  11. Identification of the RGG Box Motif in Shadoo: RNA-Binding and Signaling Roles?

    PubMed Central

    Corley, Susan M.; Gready, Jill E.

    2008-01-01

    Using comparative genomics and in-silico analyses, we previously identified a new member of the prion-protein (PrP) family, the gene SPRN, encoding the protein Shadoo (Sho), and suggested its functions might overlap with those of PrP. Extended bioinformatics and conceptual biology studies to elucidate Sho’s functions now reveal Sho has a conserved RGG-box motif, a well-known RNA-binding motif characterized in proteins such as FragileX Mental Retardation Protein. We report a systematic comparative analysis of RGG-box containing proteins which highlights the motif’s functional versatility and supports the suggestion that Sho plays a dual role in cell signaling and RNA binding in brain. These findings provide a further link to PrP, which has well-characterized RNA-binding properties. PMID:19812790

  12. Native characterization of nucleic acid motif thermodynamics via non-covalent catalysis

    NASA Astrophysics Data System (ADS)

    Wang, Chunyan; Bae, Jin H.; Zhang, David Yu

    2016-01-01

    DNA hybridization thermodynamics is critical for accurate design of oligonucleotides for biotechnology and nanotechnology applications, but parameters currently in use are inaccurately extrapolated based on limited quantitative understanding of thermal behaviours. Here, we present a method to measure the ΔG° of DNA motifs at temperatures and buffer conditions of interest, with significantly better accuracy (6- to 14-fold lower s.e.) than prior methods. The equilibrium constant of a reaction with thermodynamics closely approximating that of a desired motif is numerically calculated from directly observed reactant and product equilibrium concentrations; a DNA catalyst is designed to accelerate equilibration. We measured the ΔG° of terminal fluorophores, single-nucleotide dangles and multinucleotide dangles, in temperatures ranging from 10 to 45 °C.

  13. A Convex Atomic-Norm Approach to Multiple Sequence Alignment and Motif Discovery

    PubMed Central

    Yen, Ian E. H.; Lin, Xin; Zhang, Jiong; Ravikumar, Pradeep; Dhillon, Inderjit S.

    2016-01-01

    Multiple Sequence Alignment and Motif Discovery, known as NP-hard problems, are two fundamental tasks in Bioinformatics. Existing approaches to these two problems are based on either local search methods such as Expectation Maximization (EM), Gibbs Sampling or greedy heuristic methods. In this work, we develop a convex relaxation approach to both problems based on the recent concept of atomic norm and develop a new algorithm, termed Greedy Direction Method of Multiplier, for solving the convex relaxation with two convex atomic constraints. Experiments show that our convex relaxation approach produces solutions of higher quality than those standard tools widely-used in Bioinformatics community on the Multiple Sequence Alignment and Motif Discovery problems. PMID:27559428

  14. Super-transient scaling in time-delay autonomous Boolean network motifs.

    PubMed

    D'Huys, Otti; Lohmann, Johannes; Haynes, Nicholas D; Gauthier, Daniel J

    2016-09-01

    Autonomous Boolean networks are commonly used to model the dynamics of gene regulatory networks and allow for the prediction of stable dynamical attractors. However, most models do not account for time delays along the network links and noise, which are crucial features of real biological systems. Concentrating on two paradigmatic motifs, the toggle switch and the repressilator, we develop an experimental testbed that explicitly includes both inter-node time delays and noise using digital logic elements on field-programmable gate arrays. We observe transients that last millions to billions of characteristic time scales and scale exponentially with the amount of time delays between nodes, a phenomenon known as super-transient scaling. We develop a hybrid model that includes time delays along network links and allows for stochastic variation in the delays. Using this model, we explain the observed super-transient scaling of both motifs and recreate the experimentally measured transient distributions.

  15. Discover 1: a new program to search for unusually represented DNA motifs.

    PubMed Central

    Valle, G

    1993-01-01

    DISCOVER1 (DIStribution COunter VERsion 1) is a new program that can identify DNA motifs occurring with a high deviation from the expected frequency. The program generates families of patterns, each family having a common set of defined bases. Undefined bases are inserted amongst the defined bases in different ways, thus generating the diverse patterns of each family. The occurrences of the different patterns are then compared and analysed within each family, assuming that all patterns should have the same probability of occurrence. An extensive use of computer memory, combined with the immediate sorting of counts by address calculation allow a complete counting of all DNA motifs on a single pass on the DNA sequence. This approach offers a very fast way to search for unusually distributed patterns and can identify inexact patterns as well as exact patterns. PMID:8255770

  16. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme

    PubMed Central

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai-Zhuang; Lin, Zijing; Zhu, Zi-Zhong; Ho, Kai-Ming

    2015-01-01

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. These structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been much less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs. PMID:26497381

  17. Target motifs affecting natural immunity by a constitutive CRISPR-Cas system in Escherichia coli.

    PubMed

    Almendros, Cristóbal; Guzmán, Noemí M; Díez-Villaseñor, César; García-Martínez, Jesús; Mojica, Francisco J M

    2012-01-01

    Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR associated (cas) genes conform the CRISPR-Cas systems of various bacteria and archaea and produce degradation of invading nucleic acids containing sequences (protospacers) that are complementary to repeat intervening spacers. It has been demonstrated that the base sequence identity of a protospacer with the cognate spacer and the presence of a protospacer adjacent motif (PAM) influence CRISPR-mediated interference efficiency. By using an original transformation assay with plasmids targeted by a resident spacer here we show that natural CRISPR-mediated immunity against invading DNA occurs in wild type Escherichia coli. Unexpectedly, the strongest activity is observed with protospacer adjoining nucleotides (interference motifs) that differ from the PAM both in sequence and location. Hence, our results document for the first time native CRISPR activity in E. coli and demonstrate that positions next to the PAM in invading DNA influence their recognition and degradation by these prokaryotic immune systems.

  18. Native characterization of nucleic acid motif thermodynamics via non-covalent catalysis.

    PubMed

    Wang, Chunyan; Bae, Jin H; Zhang, David Yu

    2016-01-19

    DNA hybridization thermodynamics is critical for accurate design of oligonucleotides for biotechnology and nanotechnology applications, but parameters currently in use are inaccurately extrapolated based on limited quantitative understanding of thermal behaviours. Here, we present a method to measure the ΔG° of DNA motifs at temperatures and buffer conditions of interest, with significantly better accuracy (6- to 14-fold lower s.e.) than prior methods. The equilibrium constant of a reaction with thermodynamics closely approximating that of a desired motif is numerically calculated from directly observed reactant and product equilibrium concentrations; a DNA catalyst is designed to accelerate equilibration. We measured the ΔG° of terminal fluorophores, single-nucleotide dangles and multinucleotide dangles, in temperatures ranging from 10 to 45 °C.

  19. Identification of peptide motif that binds to the surface of zirconia.

    PubMed

    Hashimoto, Kazuhiko; Yoshinari, Masao; Matsuzaka, Kenichi; Shiba, Kiyotaka; Inoue, Takashi

    2011-01-01

    A zirconia-binding peptide motif was identified using a peptide phage display system. Yttria stabilized zirconia beads and discs were used as the target. Quartz crystal microbalance was used to monitor the binding of phages to zirconia. Starting from a library of phages displaying random sequences of 12-mer peptides, we repeated cycles of biopanning against zirconia beads. After four cycles of biopanning, we isolated a phage clone Φ#17. DNA sequencing of the corresponding portion of Φ#17 unexpectedly revealed that it displayed a 58-mer peptide (amino acid sequence: WMPSDVDINDPQGGGSRPNLHQPKPAAEAASKKKSENRKVPFYSHSWY-SSMSEDKRGW). We found that Φ#17 had a 300-fold, significantly higher binding affinity for zirconia discs than phages displaying no peptide. In quartz crystal microbalance assay, a rapid increase in energy dissipation was observed from Φ#17 but not from the control phages, indicating that Φ#17 binds to the surface of zirconia via its displayed peptide. We successfully identified a peptide motif that binds zirconia.

  20. Design and development of three-dimensional DNA crystals utilizing CGAA parallel base paired motifs

    NASA Astrophysics Data System (ADS)

    Muser, Stephanie Elizabeth

    Three-dimensional (3D) DNA crystals hold great potential for various applications such as the development of molecular scaffolds for use in protein structure determination by x-ray crystallography. The programmability and predictability of DNA make it a powerful tool for self-assembly but it is hindered by the linearity of the duplex structure. Predictable noncanonical base pairs and motifs have the potential to connect linear double-helical DNA segments into complex 3D structures. The sequence d(GCGAAAGCT) has been observed to form 3D crystals containing both noncanonical parallel pairs and canonical Watson-Crick pairs. This provided a template structure that we used in expanding the design and development of 3D DNA crystals along with exploring the use of predictable noncanonical motifs. The structures we determined contained all but one or two of the designed secondary structure interactions, depending on pH.

  1. A compendium of RNA-binding motifs for decoding gene regulation

    PubMed Central

    Ray, Debashish; Kazan, Hilal; Cook, Kate B.; Weirauch, Matthew T.; Najafabadi, Hamed S.; Li, Xiao; Gueroussov, Serge; Albu, Mihai; Zheng, Hong; Yang, Ally; Na, Hong; Irimia, Manuel; Matzat, Leah H.; Dale, Ryan K.; Smith, Sarah A.; Yarosh, Christopher A.; Kelly, Seth M.; Nabet, Behnam; Mecenas, Desirea; Li, Weimin; Laishram, Rakesh S.; Qiao, Mei; Lipshitz, Howard D.; Piano, Fabio; Corbett, Anita H.; Carstens, Russ P.; Frey, Brendan J.; Anderson, Richard A.; Lynch, Kristen W.; Penalva, Luiz O. F.; Lei, Elissa P.; Fraser, Andrew G.; Blencowe, Benjamin J.; Morris, Quaid D.; Hughes, Timothy R.

    2014-01-01

    RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence. The motifs that we identify in vitro correlate well with in vivo RNA-binding data. Moreover, we can associate them with distinct functional roles in diverse types of post-transcriptional regulation, enabling new insights into the functions of RNA-binding proteins both in normal physiology and in human disease. These data provide an unprecedented overview of RNA-binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukaryotes. PMID:23846655

  2. Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination.

    PubMed

    Myers, Simon; Bowden, Rory; Tumian, Afidalina; Bontrop, Ronald E; Freeman, Colin; MacFie, Tammie S; McVean, Gil; Donnelly, Peter

    2010-02-12

    Although present in both humans and chimpanzees, recombination hotspots, at which meiotic crossover events cluster, differ markedly in their genomic location between the species. We report that a 13-base pair sequence motif previously associated with the activity of 40% of human hotspots does not function in chimpanzees and is being removed by self-destructive drive in the human lineage. Multiple lines of evidence suggest that the rapidly evolving zinc-finger protein PRDM9 binds to this motif and that sequence changes in the protein may be responsible for hotspot differences between species. The involvement of PRDM9, which causes histone H3 lysine 4 trimethylation, implies that there is a common mechanism for recombination hotspots in eukaryotes but raises questions about what forces have driven such rapid change.

  3. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme

    SciTech Connect

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai -Zhuang; Lin, Zijing; Zhu, Zi -Zhong; Ho, Kai -Ming

    2015-10-26

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. In addition, these structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been much less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs.

  4. Spectral Barcoding of Quantum Dots: Deciphering Structural Motifs from the Excitonic Spectra

    SciTech Connect

    Mlinar, V.; Zunger, A.

    2009-01-01

    Self-assembled semiconductor quantum dots (QDs) show in high-resolution single-dot spectra a multitude of sharp lines, resembling a barcode, due to various neutral and charged exciton complexes. Here we propose the 'spectral barcoding' method that deciphers structural motifs of dots by using such barcode as input to an artificial-intelligence learning system. Thus, we invert the common practice of deducing spectra from structure by deducing structure from spectra. This approach (i) lays the foundation for building a much needed structure-spectra understanding for large nanostructures and (ii) can guide future design of desired optical features of QDs by controlling during growth only those structural motifs that decide given optical features.

  5. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme.

    PubMed

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai-Zhuang; Lin, Zijing; Zhu, Zi-Zhong; Ho, Kai-Ming

    2015-10-26

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. These structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been much less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs.

  6. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme

    DOE PAGES

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; ...

    2015-10-26

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. In addition, these structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been muchmore » less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs.« less

  7. Multiple Binding Modes between HNF4α and the LXXLL Motifs of PGC-1α Lead to Full Activation*

    PubMed Central

    Rha, Geun Bae; Wu, Guangteng; Shoelson, Steven E.; Chi, Young-In

    2009-01-01

    Hepatocyte nuclear factor 4α (HNF4α) is a novel nuclear receptor that participates in a hierarchical network of transcription factors regulating the development and physiology of such vital organs as the liver, pancreas, and kidney. Among the various transcriptional coregulators with which HNF4α interacts, peroxisome proliferation-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) represents a novel coactivator whose activation is unusually robust and whose binding mode appears to be distinct from that of canonical coactivators such as NCoA/SRC/p160 family members. To elucidate the potentially unique molecular mechanism of PGC-1α recruitment, we have determined the crystal structure of HNF4α in complex with a fragment of PGC-1α containing all three of its LXXLL motifs. Despite the presence of all three LXXLL motifs available for interactions, only one is bound at the canonical binding site, with no additional contacts observed between the two proteins. However, a close inspection of the electron density map indicates that the bound LXXLL motif is not a selected one but an averaged structure of more than one LXXLL motif. Further biochemical and functional studies show that the individual LXXLL motifs can bind but drive only minimal transactivation. Only when more than one LXXLL motif is involved can significant transcriptional activity be measured, and full activation requires all three LXXLL motifs. These findings led us to propose a model wherein each LXXLL motif has an additive effect, and the multiple binding modes by HNF4α toward the LXXLL motifs of PGC-1α could account for the apparent robust activation by providing a flexible mechanism for combinatorial recruitment of additional coactivators and mediators. PMID:19846556

  8. The immunostimulatory activity of CpG oligonucleotides on microglial N9 cells is affected by a polyguanosine motif.

    PubMed

    Zhang, Zhiren; Guo, Ketai; Schluesener, Hermann J

    2005-04-01

    Oligonucleotides (ODN) with hexameric motifs containing central unmethylated CpG dinucleotides are immunostimulatory. Also ODN with continuous guanosines (polyG motif) show a wide range of immunological activity. Depending on the position, the chemical property of the ODN backbone and the cell type, polyG motifs have either an enhancing or a suppressing effect on the immunostimulatory activity of the CpG-ODN. Microglial cells are central components of the innate immune system of the brain and are activated by CpG-ODN in vitro and in vivo. Here we present the analysis of the immunomodulatory effects of CpG-ODN carrying a polyG motif on the microglial cell line N9. Our data show that N9 cells express Toll-like receptor 9 (TLR9) and are activated by CpG-ODN, which leads to expression of interleukin-12p40 (IL12p40), tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). A 3'-end polyG motif inhibits phosphothioate (PS) CpG-ODN immunostimulatory activity but enhances the immunostimulatory activity of phosphodiester (PE) CpG-ODN. Correspondingly, a 3'-end polyG motif improves the cellular uptake of PE CpG-ODN but does not change their cellular distribution pattern. Furthermore, PE CpG-ODN with a 3'-end polyG motif interact with a much higher number of cellular proteins than PE CpG-ODN. These data indicate that the 3'-end polyG motif could enhance the immunostimulatory activity of PE CpG-ODN in microglial N9 cells through increasing interaction with cellular proteins. Therefore PE CpG-ODN containing a 3'-end polyG motif resulting in increased immunostimulatory activity might be promising alternate analogues for studies in the central nervous system.

  9. Evaluation of diverse peptidyl motifs for cellular delivery of semiconductor quantum dots.

    PubMed

    Gemmill, Kelly Boeneman; Muttenthaler, Markus; Delehanty, James B; Stewart, Michael H; Susumu, Kimihiro; Dawson, Philip E; Medintz, Igor L

    2013-07-01

    Cell-penetrating peptides (CPPs) have rapidly become a mainstay technology for facilitating the delivery of a wide variety of nanomaterials to cells and tissues. Currently, the library of CPPs to choose from is still limited, with the HIV TAT-derived motif still being the most used. Among the many materials routinely delivered by CPPs, nanoparticles are of particular interest for a plethora of labeling, imaging, sensing, diagnostic, and therapeutic applications. The development of nanoparticle-based technologies for many of these uses will require access to a much larger number of functional peptide motifs that can both facilitate cellular delivery of different types of nanoparticles to cells and be used interchangeably in the presence of other peptides and proteins on the same surface. Here, we evaluate the utility of four peptidyl motifs for their ability to facilitate delivery of luminescent semiconductor quantum dots (QDs) in a model cell culture system. We find that an LAH4 motif, derived from a membrane-inserting antimicrobial peptide, and a chimeric sequence that combines a sweet arrow peptide with a portion originating from the superoxide dismutase enzyme provide effective cellular delivery of QDs. Interestingly, a derivative of the latter sequence lacking just a methyl group was found to be quite inefficient, suggesting that even small changes can have significant functional outcomes. Delivery was effected using 1 h incubation with cells, and fluorescent counterstaining strongly suggests an endosomal uptake process that requires a critical minimum number or ratio of peptides to be displayed on the QD surface. Concomitant cytoviability testing showed that the QD-peptide conjugates are minimally cytotoxic in the model COS-1 cell line tested. Potential applications of these peptides in the context of cellular delivery of nanoparticles and a variety of other (bio)molecules are discussed.

  10. In vivo immunogold labeling confirms large-scale chromatin folding motifs.

    PubMed

    Kireev, Igor; Lakonishok, Margot; Liu, Wenqiu; Joshi, Vishwas N; Powell, Rick; Belmont, Andrew S

    2008-04-01

    The difficulty in localizing specific cellular proteins by immuno-electron microscopy techniques limits applications of electron microscopy to cell biology. We found that in vivo immunogold labeling improves epitope accessibility, ultrastructural preservation and three-dimensional visualization, and allows correlated light and electron microscopy. We detected large-scale chromatin folding motifs within intact interphase nuclei of CHO cells and visualized the ultrastructure of DNA replication 'factories' labeled with GFP-proliferating cell nuclear antigen (PCNA).

  11. Systematic reconstruction of RNA functional motifs with high-throughput microfluidics.

    PubMed

    Martin, Lance; Meier, Matthias; Lyons, Shawn M; Sit, Rene V; Marzluff, William F; Quake, Stephen R; Chang, Howard Y

    2012-12-01

    We present RNA-mechanically induced trapping of molecular interactions (RNA-MITOMI), a microfluidic platform that allows integrated synthesis and functional assays for programmable RNA libraries. The interaction of a comprehensive library of RNA mutants with stem-loop-binding protein precisely defined the RNA structural and sequence features that govern affinity. The functional motif reconstructed in a single experiment on our platform uncovers new binding specificities and enriches interpretation of phylogenetic data.

  12. A Novel Fibronectin Binding Motif in MSCRAMMs Targets F3 Modules

    PubMed Central

    Prabhakaran, Sabitha; Liang, Xiaowen; Skare, Jonathan T.; Potts, Jennifer R.; Höök, Magnus

    2009-01-01

    Background BBK32 is a surface expressed lipoprotein and fibronectin (Fn)-binding microbial surface component recognizing adhesive matrix molecule (MSCRAMM) of Borrelia burgdorferi, the causative agent of Lyme disease. Previous studies from our group showed that BBK32 is a virulence factor in experimental Lyme disease and located the Fn-binding region to residues 21–205 of the lipoprotein. Methodology/Principal Findings Studies aimed at identifying interacting sites between BBK32 and Fn revealed an interaction between the MSCRAMM and the Fn F3 modules. Further analysis of this interaction showed that BBK32 can cause the aggregation of human plasma Fn in a similar concentration-dependent manner to that of anastellin, the superfibronectin (sFn) inducing agent. The resulting Fn aggregates are conformationally distinct from plasma Fn as indicated by a change in available thermolysin cleavage sites. Recombinant BBK32 and anastellin affect the structure of Fn matrices formed by cultured fibroblasts and inhibit endothelial cell proliferation similarly. Within BBK32, we have located the sFn-forming activity to a region between residues 160 and 175 which contains two sequence motifs that are also found in anastellin. Synthetic peptides mimicking these motifs induce Fn aggregation, whereas a peptide with a scrambled sequence motif was inactive, suggesting that these motifs represent the sFn-inducing sequence. Conclusions/Significance We conclude that BBK32 induces the formation of Fn aggregates that are indistinguishable from those formed by anastellin. The results of this study provide evidence for how bacteria can target host proteins to manipulate host cell activities. PMID:19404402

  13. Analysis of the DXD motifs in human xylosyltransferase I required for enzyme activity.

    PubMed

    Götting, Christian; Müller, Sandra; Schöttler, Manuela; Schön, Sylvia; Prante, Christian; Brinkmann, Thomas; Kuhn, Joachim; Kleesiek, Knut

    2004-10-08

    Human xylosyltransferase I (XT-I) is the initial enzyme involved in the biosynthesis of the glycosaminoglycan linker region in proteoglycans. Here, we tested the importance of the DXD motifs at positions 314-316 and 745-747 for enzyme activity and the nucleotide binding capacity of human XT-I. Mutations of the 314DED316 motif did not have any effect on enzyme activity, whereas alterations of the 745DWD747 motif resulted in reduced XT-I activity. Loss of function was observed after exchange of the highly conserved aspartic acid at position 745 with glycine. However, mutation of Asp745 to glutamic acid retained full enzyme activity, indicating the importance of an acidic amino acid at this position. Reduced substrate affinity was observed for mutants D747G (Km=6.9 microm) and D747E (Km=4.4 microm) in comparison with the wild-type enzyme (Km=0.9 microm). Changing the central tryptophan to a neutral, basic, or acidic amino acid resulted in a 6-fold lower Vmax, with Km values comparable with those of the wild-type enzyme. Despite the major effect of the DWD motif on XT-I activity, nucleotide binding was not abolished in the D745G and D747G mutants, as revealed by UDP-bead binding assays. Ki values for inhibition by UDP were determined to be 1.9-24.6 microm for the XT-I mutants. The properties of binding of XT-I to heparin-beads, the Ki constants for noncompetitive inhibition by heparin, and the activation by protamine were not altered by the generated mutations.

  14. Reusable amine-based structural motifs for green house gas (CO2) fixation.

    PubMed

    Dalapati, Sasanka; Jana, Sankar; Saha, Rajat; Alam, Md Akhtarul; Guchhait, Nikhil

    2012-07-06

    A series of compounds with an amine based structural motif (ASM) have been synthesized for efficient atmospheric CO(2) fixation. The H-bonded ASM-bicarbonate complexes were formed with an in situ generated HCO(3)(-) ion. The complexes have been characterized by IR, (13)C NMR, and X-ray single-crystal structural analysis. ASM-bicarbonate salts have been converted to pure ASMs in quantitative yield under mild conditions for recycling processes.

  15. Conserved Hydration Sites in Pin1 Reveal a Distinctive Water Recognition Motif in Proteins.

    PubMed

    Barman, Arghya; Smitherman, Crystal; Souffrant, Michael; Gadda, Giovanni; Hamelberg, Donald

    2016-01-25

    Structurally conserved water molecules are important for biomolecular stability, flexibility, and function. X-ray crystallographic studies of Pin1 have resolved a number of water molecules around the enzyme, including two highly conserved water molecules within the protein. The functional role of these localized water molecules remains unknown and unexplored. Pin1 catalyzes cis/trans isomerizations of peptidyl prolyl bonds that are preceded by a phosphorylated serine or threonine residue. Pin1 is involved in many subcellular signaling processes and is a potential therapeutic target for the treatment of several life threatening diseases. Here, we investigate the significance of these structurally conserved water molecules in the catalytic domain of Pin1 using molecular dynamics (MD) simulations, free energy calculations, analysis of X-ray crystal structures, and circular dichroism (CD) experiments. MD simulations and free energy calculations suggest the tighter binding water molecule plays a crucial role in maintaining the integrity and stability of a critical hydrogen-bonding network in the active site. The second water molecule is exchangeable with bulk solvent and is found in a distinctive helix-turn-coil motif. Structural bioinformatics analysis of nonredundant X-ray crystallographic protein structures in the Protein Data Bank (PDB) suggest this motif is present in several other proteins and can act as a water site, akin to the calcium EF hand. CD experiments suggest the isolated motif is in a distorted PII conformation and requires the protein environment to fully form the α-helix-turn-coil motif. This study provides valuable insights into the role of hydration in the structural integrity of Pin1 that can be exploited in protein engineering and drug design.

  16. Sevoflurane Alters Spatiotemporal Functional Connectivity Motifs That Link Resting-State Networks during Wakefulness

    PubMed Central

    Kafashan, MohammadMehdi; Ching, ShiNung; Palanca, Ben J. A.

    2016-01-01

    Background: The spatiotemporal patterns of correlated neural activity during the transition from wakefulness to general anesthesia have not been fully characterized. Correlation analysis of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) allows segmentation of the brain into resting-state networks (RSNs), with functional connectivity referring to the covarying activity that suggests shared functional specialization. We quantified the persistence of these correlations following the induction of general anesthesia in healthy volunteers and assessed for a dynamic nature over time. Methods: We analyzed human fMRI data acquired at 0 and 1.2% vol sevoflurane. The covariance in the correlated activity among different brain regions was calculated over time using bounded Kalman filtering. These time series were then clustered into eight orthogonal motifs using a K-means algorithm, where the structure of correlated activity throughout the brain at any time is the weighted sum of all motifs. Results: Across time scales and under anesthesia, the reorganization of interactions between RSNs is related to the strength of dynamic connections between member pairs. The covariance of correlated activity between RSNs persists compared to that linking individual member pairs of different RSNs. Conclusions: Accounting for the spatiotemporal structure of correlated BOLD signals, anesthetic-induced loss of consciousness is mainly associated with the disruption of motifs with intermediate strength within and between members of different RSNs. In contrast, motifs with higher strength of connections, predominantly with regions-pairs from within-RSN interactions, are conserved among states of wakefulness and sevoflurane general anesthesia. PMID:28082871

  17. Targeting MED1 LxxLL Motifs for Tissue-Selective Treatment of Human Breast Cancer

    DTIC Science & Technology

    2012-09-01

    pRNA nanoparticle delivery system has been used to conjugate CD4 aptamers and anti-GP120 aptamers, and was tested in anti- cancer and viral infection... nanoparticles for specific delivery of multiple therapeutic molecules to cancer cells using RNA nanotechnology . Nano Lett 5, 1797-1808. Khvorova, A...estrogen receptor interacting NR boxes/LxxLL motifs of the MED1 protein and test their efficacy on breast cancer cell growth both in vitro and in

  18. An evolutionary analysis of flightin reveals a conserved motif unique and widespread in Pancrustacea.

    PubMed

    Soto-Adames, Felipe N; Alvarez-Ortiz, Pedro; Vigoreaux, Jim O

    2014-01-01

    Flightin is a thick filament protein that in Drosophila melanogaster is uniquely expressed in the asynchronous, indirect flight muscles (IFM). Flightin is required for the structure and function of the IFM and is indispensable for flight in Drosophila. Given the importance of flight acquisition in the evolutionary history of insects, here we study the phylogeny and distribution of flightin. Flightin was identified in 69 species of hexapods in classes Collembola (springtails), Protura, Diplura, and insect orders Thysanura (silverfish), Dictyoptera (roaches), Orthoptera (grasshoppers), Pthiraptera (lice), Hemiptera (true bugs), Coleoptera (beetles), Neuroptera (green lacewing), Hymenoptera (bees, ants, and wasps), Lepidoptera (moths), and Diptera (flies and mosquitoes). Flightin was also found in 14 species of crustaceans in orders Anostraca (water flea), Cladocera (brine shrimp), Isopoda (pill bugs), Amphipoda (scuds, sideswimmers), and Decapoda (lobsters, crabs, and shrimps). Flightin was not identified in representatives of chelicerates, myriapods, or any species outside Pancrustacea (Tetraconata, sensu Dohle). Alignment of amino acid sequences revealed a conserved region of 52 amino acids, referred herein as WYR, that is bound by strictly conserved tryptophan (W) and arginine (R) and an intervening sequence with a high content of tyrosines (Y). This motif has no homologs in GenBank or PROSITE and is unique to flightin and paraflightin, a putative flightin paralog identified in decapods. A third motif of unclear affinities to pancrustacean WYR was observed in chelicerates. Phylogenetic analysis of amino acid sequences of the conserved motif suggests that paraflightin originated before the divergence of amphipods, isopods, and decapods. We conclude that flightin originated de novo in the ancestor of Pancrustacea > 500 MYA, well before the divergence of insects (~400 MYA) and the origin of flight (~325 MYA), and that its IFM-specific function in Drosophila is a more

  19. Systems chemistry: logic gates, arithmetic units, and network motifs in small networks.

    PubMed

    Wagner, Nathaniel; Ashkenasy, Gonen

    2009-01-01

    A mixture of molecules can be regarded as a network if all the molecular components participate in some kind of interaction with other molecules--either physical or functional interactions. Template-assisted ligation reactions that direct replication processes can serve as the functional elements that connect two members of a chemical network. In such a process, the template does not necessarily catalyze its own formation, but rather the formation of another molecule, which in turn can operate as a template for reactions within the network medium. It was postulated that even networks made up of small numbers of molecules possess a wealth of molecular information sufficient to perform rather complex behavior. To probe this assumption, we have constructed virtual arrays consisting of three replicating molecules, in which dimer templates are capable of catalyzing reactants to form additional templates. By using realistic parameters from peptides or DNA replication experiments, we simulate the construction of various functional motifs within the networks. Specifically, we have designed and implemented each of the three-element Boolean logic gates, and show how these networks are assembled from four basic "building blocks". We also show how the catalytic pathways can be wired together to perform more complex arithmetic units and network motifs, such as the half adder and half subtractor computational modules, and the coherent feed-forward loop network motifs under different sets of parameters. As in previous studies of chemical networks, some of the systems described display behavior that would be difficult to predict without the numerical simulations. Furthermore, the simulations reveal trends and characteristics that should be useful as "recipes" for future design of experimental functional motifs and for potential integration into modular circuits and molecular computation devices.

  20. Motif analysis for small-number effects in chemical reaction dynamics.

    PubMed

    Saito, Nen; Sughiyama, Yuki; Kaneko, Kunihiko

    2016-09-07

    The number of molecules involved in a cell or subcellular structure is sometimes rather small. In this situation, ordinary macroscopic-level fluctuations can be overwhelmed by non-negligible large fluctuations, which results in drastic changes in chemical-reaction dynamics and statistics compared to those observed under a macroscopic system (i.e., with a large number of molecules). In order to understand how salient changes emerge from fluctuations in molecular number, we here quantitatively define small-number effect by focusing on a "mesoscopic" level, in which the concentration distribution is distinguishable both from micro- and macroscopic ones and propose a criterion for determining whether or not such an effect can emerge in a given chemical reaction network. Using the proposed criterion, we systematically derive a list of motifs of chemical reaction networks that can show small-number effects, which includes motifs showing emergence of the power law and the bimodal distribution observable in a mesoscopic regime with respect to molecule number. The list of motifs provided herein is helpful in the search for candidates of biochemical reactions with a small-number effect for possible biological functions, as well as for designing a reaction system whose behavior can change drastically depending on molecule number, rather than concentration.

  1. Ubiquitous presence of the hammerhead ribozyme motif along the tree of life

    PubMed Central

    de la Peña, Marcos; García-Robles, Inmaculada

    2010-01-01

    Examples of small self-cleaving RNAs embedded in noncoding regions already have been found to be involved in the control of gene expression, although their origin remains uncertain. In this work, we show the widespread occurrence of the hammerhead ribozyme (HHR) motif among genomes from the Bacteria, Chromalveolata, Plantae, and Metazoa kingdoms. Intergenic HHRs were detected in three different bacterial genomes, whereas metagenomic data from Galapagos Islands showed the occurrence of similar ribozymes that could be regarded as direct relics from the RNA world. Among eukaryotes, HHRs were detected in the genomes of three water molds as well as 20 plant species, ranging from unicellular algae to vascular plants. These HHRs were very similar to those previously described in small RNA plant pathogens and, in some cases, appeared as close tandem repetitions. A parallel situation of tandemly repeated HHR motifs was also detected in the genomes of lower metazoans from cnidarians to invertebrates, with special emphasis among hematophagous and parasitic organisms. Altogether, these findings unveil the HHR as a widespread motif in DNA genomes, which would be involved in new forms of retrotransposable elements. PMID:20705646

  2. Identification of a pKa-regulating motif stabilizing imidazole-modified double-stranded DNA

    PubMed Central

    Buyst, Dieter; Gheerardijn, Vicky; Fehér, Krisztina; Van Gasse, Bjorn; Van Den Begin, Jos; Martins, José C.; Madder, Annemieke

    2015-01-01

    The predictable 3D structure of double-stranded DNA renders it ideally suited as a template for the bottom-up design of functionalized nucleic acid-based active sites. We here explore the use of a 14mer DNA duplex as a scaffold for the precise and predictable positioning of catalytic functionalities. Given the ubiquitous participation of the histidine-based imidazole group in protein recognition and catalysis events, single histidine-like modified duplexes were investigated. Tethering histamine to the C5 of the thymine base via an amide bond, allows the flexible positioning of the imidazole function in the major groove. The mutual interactions between the imidazole and the duplex and its influence on the imidazolium pKaH are investigated by placing a single modified thymine at four different positions in the center of the 14mer double helix. Using NMR and unrestrained molecular dynamics, a structural motif involving the formation of a hydrogen bond between the imidazole and the Hoogsteen side of the guanine bases of two neighboring GC base pairs is established. The motif contributes to a stabilization against thermal melting of 6°C and is key in modulating the pKaH of the imidazolium group. The general features, prerequisites and generic character of the new pKaH-regulating motif are described. PMID:25520197

  3. Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein

    PubMed Central

    Choi, IL-Whan; Ahn, Do Whan; Choi, Jang-Kyu; Cha, Hee-Jae; Ock, Mee Sun; You, EunAe; Rhee, SangMyung; Kim, Kwang Chul; Choi, Yung Hyun; Song, Kyoung Seob

    2016-01-01

    Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and lung infections have critical consequences on mortality and morbidity in humans. The aims of the present study were to examine the mechanisms by which CXCL12 affects MUC1 transcription and airway inflammation, which depend on activator of G-protein signaling (AGS) 3 and to identify specific molecules that suppress CXCL12-induced airway inflammation by acting on G-protein-coupled receptors. Herein, AGS3 suppresses CXCL12-mediated upregulation of MUC1 and TNFα by regulating Gαi. We found that the G-protein regulatory (GPR) motif peptide in AGS3 binds to Gαi and downregulates MUC1 expression; in contrast, this motif upregulates TNFα expression. Mutated GPR Q34A peptide increased the expression of MUC1 and TGFβ but decreased the expression of TNFα and IL-6. Moreover, CXCR4-induced dendritic extensions in 2D and 3D matrix cultures were inhibited by the GPR Q34A peptide compared with a wild-type GPR peptide. The GPR Q34A peptide also inhibited CXCL12-induced morphological changes and inflammatory cell infiltration in the mouse lung, and production of inflammatory cytokines in bronchoalveolar lavage (BAL) fluid and the lungs. Our data indicate that the GPR motif of AGS3 is critical for regulating MUC1/Muc1 expression and cytokine production in the inflammatory microenvironment. PMID:27270970

  4. Identification of putative DnaN-binding motifs in plasmid replication initiation proteins.

    PubMed

    Dalrymple, Brian P; Kongsuwan, Kritaya; Wijffels, Gene

    2007-01-01

    Recently the plasmid RK2 replication initiation protein, TrfA, has been shown to bind to the beta subunit of DNA Polymerase III (DnaN) via a short pentapeptide with the consensus QL[S/D]LF. A second consensus peptide, the hexapeptide QLxLxL, has also been demonstrated to mediate binding to DnaN. Here we describe the results of a comprehensive survey of replication initiation proteins encoded by bacterial plasmids to identify putative DnaN-binding sites. Both pentapeptide and hexapeptide motifs have been identified in a number of families of replication initiation proteins. The distribution of sites is sporadic and closely related families of proteins may differ in the presence, location, or type of putative DnaN-binding motif. Neither motif has been identified in replication initiation proteins encoded by plasmids that replicate via rolling circles or strand displacement. The results suggest that the recruitment of DnaN to the origin of replication of a replisome by plasmid replication initiation proteins is not generally required for plasmid replication, but that in some cases it may be beneficial for efficiency of replication initiation.

  5. The tungsten formylmethanofuran dehydrogenase from Methanobacterium thermoautotrophicum contains sequence motifs characteristic for enzymes containing molybdopterin dinucleotide.

    PubMed

    Hochheimer, A; Schmitz, R A; Thauer, R K; Hedderich, R

    1995-12-15

    Formylmethanofuran dehydrogenases are molybdenum or tungsten iron-sulfur proteins containing a pterin dinucleotide cofactor. We report here on the primary structures of the four subunits FwdABCD of the tungsten enzyme from Methanobacterium thermoautotrophicum which were determined by cloning and sequencing the encoding genes fwdABCD. FwdB was found to contain sequence motifs characteristic for molybdopterin-dinucleotide-containing enzymes indicating that this subunit harbors the active site. FwdA, FwdC and FwdD showed no significant sequence similarity to proteins in the data bases. Northern blot analysis revealed that the four fwd genes form a transcription unit together with three additional genes designated fwdE, fwdF and fwdG. A 17.8-kDa protein and an 8.6-kDa protein, both containing two [4Fe-4S] cluster binding motifs, were deduced from fwdE and fwdG. The open reading frame fwdF encodes a 38.6-kDa protein containing eight binding motifs for [4Fe-4S] clusters suggesting the gene product to be a novel polyferredoxin. All seven fwd genes were expressed in Escherichia coli yielding proteins of the expected size. The fwd operon was found to be located in a region of the M. thermoautotrophicum genome encoding molybdenum enzymes and proteins involved in molybdopterin biosynthesis.