BMC Structural Biology最新文献

{"title":"Structuprint: a scalable and extensible tool for two-dimensional representation of protein surfaces","authors":"Dimitrios Georgios Kontopoulos,&nbsp;Dimitrios Vlachakis,&nbsp;Georgia Tsiliki,&nbsp;Sofia Kossida","doi":"10.1186/s12900-016-0055-7","DOIUrl":"https://doi.org/10.1186/s12900-016-0055-7","url":null,"abstract":"<p>The term ‘molecular cartography’ encompasses a family of computational methods for two-dimensional transformation of protein structures and analysis of their physicochemical properties. The underlying algorithms comprise multiple manual steps, whereas the few existing implementations typically restrict the user to a very limited set of molecular descriptors.</p><p>We present Structuprint, a free standalone software that fully automates the rendering of protein surface maps, given?- at the very least - a directory with a PDB file and an amino acid property. The tool comes with a default database of 328 descriptors, which can be extended or substituted by user-provided ones. The core algorithm comprises the generation of a mould of the protein surface, which is subsequently converted to a sphere and mapped to two dimensions, using the Miller cylindrical projection. Structuprint is partly optimized for multicore computers, making the rendering of animations of entire molecular dynamics simulations feasible.</p><p>Structuprint is an efficient application, implementing a molecular cartography algorithm for protein surfaces. According to the results of a benchmark, its memory requirements and execution time are reasonable, allowing it to run even on low-end personal computers. We believe that it will be of use?- primarily but not exclusively - to structural biologists and computational biochemists.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"16 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2016-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-016-0055-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4924492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure and functional implications of the tandem-type universal stress protein UspE from Escherichia coli","authors":"Yongbin Xu,&nbsp;Jianyun Guo,&nbsp;Xiaoling Jin,&nbsp;Jin-Sik Kim,&nbsp;Ying Ji,&nbsp;Shengdi Fan,&nbsp;Nam-Chul Ha,&nbsp;Chun-Shan Quan","doi":"10.1186/s12900-016-0053-9","DOIUrl":"https://doi.org/10.1186/s12900-016-0053-9","url":null,"abstract":"<p>The universal stress proteins (USP) family member UspE is a tandem-type USP that consists of two Usp domains. The UspE expression levels of the <i>Escherichia coli</i> (<i>E. coli</i>) become elevated in response to oxidative stress and DNA damaging agents, including exposure to mitomycin C, cadmium, and hydrogen peroxide. It has been shown that UspA family members are survival factors during cellular growth arrest. The structures and functions of the UspA family members control the growth of <i>E. coli</i> in animal hosts. While several UspA family members have known structures, the structure of <i>E. coli</i> UspE remains to be elucidated.</p><p>To understand the biochemical function of UspE, we have determined the crystal structure of <i>E. coli</i> UspE at 3.2?? resolution. The asymmetric unit contains two protomers related by a non-crystallographic symmetry, and each protomer contains two tandem Usp domains. The crystal structure shows that UspE is folded into a fan-shaped structure similar to that of the tandem-type Usp protein PMI1202 from <i>Proteus mirabilis</i>, and it has a hydrophobic cavity that binds its ligand. Structural analysis revealed that <i>E. coli</i> UspE has two metal ion binding sites, and isothermal titration calorimetry suggested the presence of two Cd²⁺ binding sites with a K_d value of 38.3–242.7?μM. Structural analysis suggested that <i>E. coli</i> UspE has two Cd²⁺ binding sites (Site I: His117, His 119; Site II: His193, His244).</p><p>The results show that the UspE structure has a hydrophobic pocket. This pocket is strongly bound to an unidentified ligand. Combined with a previous study, the ligand is probably related to an intermediate in lipid A biosynthesis. Subsequently, sequence analysis found that UspE has an ATP binding motif (Gly²⁶⁹- X₂-Gly²⁷²-X₉-Gly²⁸²-Asn) in its C-terminal domain, which was confirmed by <i>in vitro</i> ATPase activity monitored using Kinase-Glo? Luminescent Kinase Assay. However, the residues constituting this motif were disordered in the crystal structure, reflecting their intrinsic flexibility. ITC experiments revealed that the UspE probably has two Cd²⁺ binding sites. The His117, His 119, His193, and His244 residues within the β-barrel domain are necessary for Cd²⁺ binding to UspE protein. As mentioned above, USPs are associated with several functions, such as cadmium binding, ATPase function, and involvement in lipid A biosynthesis by some unknown way.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"16 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2016-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-016-0053-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4447680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMC Structural Biology reviewer acknowledgement 2015","authors":"Julia Simundza","doi":"10.1186/s12900-016-0054-8","DOIUrl":"https://doi.org/10.1186/s12900-016-0054-8","url":null,"abstract":"","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"16 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2016-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-016-0054-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4376456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crystal structure of the Hazara virus nucleocapsid protein","authors":"Rebecca Surtees,&nbsp;Antonio Ariza,&nbsp;Emma K. Punch,&nbsp;Chi H. Trinh,&nbsp;Stuart D. Dowall,&nbsp;Roger Hewson,&nbsp;Julian A. Hiscox,&nbsp;John N. Barr,&nbsp;Thomas A. Edwards","doi":"10.1186/s12900-015-0051-3","DOIUrl":"https://doi.org/10.1186/s12900-015-0051-3","url":null,"abstract":"<p>Hazara virus (HAZV) is a member of the <i>Bunyaviridae</i> family of segmented negative stranded RNA viruses, and shares the same serogroup as Crimean-Congo haemorrhagic fever virus (CCHFV). CCHFV is responsible for fatal human disease with a mortality rate approaching 30 %, which has an increased recent incidence within southern Europe. There are no preventative or therapeutic treatments for CCHFV-mediated disease, and thus CCHFV is classified as a hazard group 4 pathogen. In contrast HAZV is not associated with serious human disease, although infection of interferon receptor knockout mice with either CCHFV or HAZV results in similar disease progression. To characterise further similarities between HAZV and CCHFV, and support the use of HAZV as a model for CCHFV infection, we investigated the structure of the HAZV nucleocapsid protein (N) and compared it to CCHFV N. N performs an essential role in the viral life cycle by encapsidating the viral RNA genome, and thus, N represents a potential therapeutic target.</p><p>We present the purification, crystallisation and crystal structure of HAZV N at 2.7 ? resolution. HAZV N was expressed as an N-terminal glutathione S-transferase (GST) fusion protein then purified using glutathione affinity chromatography followed by ion-exchange chromatography. HAZV N crystallised in the P2₁2₁2₁ space group with unit cell parameters <i>a</i> = 64.99, <i>b</i> = 76.10, and <i>c</i> = 449.28 ?. HAZV N consists of a globular domain formed mostly of alpha helices derived from both the N- and C-termini, and an arm domain comprising two long alpha helices. HAZV N has a similar overall structure to CCHFV N, with their globular domains superposing with an RMSD = 0.70 ?, over 368 alpha carbons that share 59 % sequence identity. Four HAZV N monomers crystallised in the asymmetric unit, and their head-to-tail assembly reveals a potential interaction site between monomers.</p><p>The crystal structure of HAZV N reveals a close similarity to CCHFV N, supporting the use of HAZV as a model for CCHFV. Structural similarity between the N proteins should facilitate study of the CCHFV and HAZV replication cycles without the necessity of working under containment level 4 (CL-4) conditions.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"15 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2015-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-015-0051-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5110646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicted binding site information improves model ranking in protein docking using experimental and computer-generated target structures","authors":"Surabhi Maheshwari,&nbsp;Michal Brylinski","doi":"10.1186/s12900-015-0050-4","DOIUrl":"https://doi.org/10.1186/s12900-015-0050-4","url":null,"abstract":"<p>Protein-protein interactions (PPIs) mediate the vast majority of biological processes, therefore, significant efforts have been directed to investigate PPIs to fully comprehend cellular functions. Predicting complex structures is critical to reveal molecular mechanisms by which proteins operate. Despite recent advances in the development of new methods to model macromolecular assemblies, most current methodologies are designed to work with experimentally determined protein structures. However, because only computer-generated models are available for a large number of proteins in a given genome, computational tools should tolerate structural inaccuracies in order to perform the genome-wide modeling of PPIs.</p><p>To address this problem, we developed <i>e</i>Rank^PPI, an algorithm for the identification of near-native conformations generated by protein docking using experimental structures as well as protein models. The scoring function implemented in <i>e</i>Rank^PPI employs multiple features including interface probability estimates calculated by <i>e</i>FindSite^PPI and a novel contact-based symmetry score. In comparative benchmarks using representative datasets of homo- and hetero-complexes, we show that <i>e</i>Rank^PPI consistently outperforms state-of-the-art algorithms improving the success rate by ~10?%.</p><p>\u0000 <i>e</i>Rank^PPI was designed to bridge the gap between the volume of sequence data, the evidence of binary interactions, and the atomic details of pharmacologically relevant protein complexes. Tolerating structure imperfections in computer-generated models opens up a possibility to conduct the exhaustive structure-based reconstruction of PPI networks across proteomes. The methods and datasets used in this study are available at www.brylinski.org/erankppi.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"15 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2015-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-015-0050-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4906537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clustering and percolation in protein loop structures","authors":"Xubiao Peng,&nbsp;Jianfeng He,&nbsp;Antti J. Niemi","doi":"10.1186/s12900-015-0049-x","DOIUrl":"https://doi.org/10.1186/s12900-015-0049-x","url":null,"abstract":"<p>High precision protein loop modelling remains a challenge, both in template based and template independent approaches to protein structure prediction.</p><p>We introduce the concepts of protein loop clustering and percolation, to develop a quantitative approach to systematically classify the modular building blocks of loops in crystallographic folded proteins. These fragments are all different parameterisations of a unique kink solution to a generalised discrete nonlinear Schr?dinger (DNLS) equation. Accordingly, the fragments are also local energy minima of the ensuing energy function.</p><p>We show how the loop fragments cover practically all ultrahigh resolution crystallographic protein structures in Protein Data Bank (PDB), with a 0.2 ?ngstr?m root-mean-square (RMS) precision. We find that no more than 12 different loop fragments are needed, to describe around 38 % of ultrahigh resolution loops in PDB. But there is also a large number of loop fragments that are either unique, or very rare, and examples of unique fragments are found even in the structure of a myoglobin.</p><p>Protein loops are built in a modular fashion. The loops are composed of fragments that can be modelled by the kink of the DNLS equation. The majority of loop fragments are also common, which are shared by many proteins. These common fragments are probably important for supporting the overall protein conformation. But there are also several fragments that are either unique to a given protein, or very rare. Such fragments are probably related to the function of the protein. Furthermore, we have found that the amino acid sequence does not determine the structure in a unique fashion. There are many examples of loop fragments with an identical amino acid sequence, but with a very different structure.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"15 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2015-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-015-0049-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5134385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional structure model and predicted ATP interaction rewiring of a deviant RNA ligase 2","authors":"Sandrine Moreira,&nbsp;Emmanuel Noutahi,&nbsp;Guillaume Lamoureux,&nbsp;Gertraud Burger","doi":"10.1186/s12900-015-0046-0","DOIUrl":"https://doi.org/10.1186/s12900-015-0046-0","url":null,"abstract":"<p>RNA ligases 2 are scarce and scattered across the tree of life. Two members of this family are well studied: the mitochondrial RNA editing ligase from the parasitic trypanosomes (Kinetoplastea), a promising drug target, and bacteriophage T4 RNA ligase 2, a workhorse in molecular biology. Here we report the identification of a divergent RNA ligase 2 (DpRNL) from <i>Diplonema papillatum</i> (Diplonemea), a member of the kinetoplastids’ sister group.</p><p>We identified DpRNL with methods based on sensitive hidden Markov Model. Then, using homology modeling and molecular dynamics simulations, we established a three dimensional structure model of DpRNL complexed with ATP and Mg2+.</p><p>The 3D model of <i>Diplonema</i> was compared with available crystal structures from <i>Trypanosoma brucei</i>, bacteriophage T4, and two archaeans. Interaction of DpRNL with ATP is predicted to involve double π-stacking, which has not been reported before in RNA ligases. This particular contact would shift the orientation of ATP and have considerable consequences on the interaction network of amino acids in the catalytic pocket. We postulate that certain canonical amino acids assume different functional roles in DpRNL compared to structurally homologous residues in other RNA ligases 2, a reassignment indicative of constructive neutral evolution. Finally, both structure comparison and phylogenetic analysis show that DpRNL is not specifically related to RNA ligases from trypanosomes, suggesting a unique adaptation of the latter for RNA editing, after the split of diplonemids and kinetoplastids.</p><p>Homology modeling and molecular dynamics simulations strongly suggest that DpRNL is an RNA ligase 2. The predicted innovative reshaping of DpRNL’s catalytic pocket is worthwhile to be tested experimentally.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"15 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2015-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-015-0046-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4709602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to: Structural characterization of the carbohydrate-binding module of NanA sialidase, a pneumococcal virulence factor","authors":"Lei Yang,&nbsp;Helen Connaris,&nbsp;Jane A. Potter,&nbsp;Garry L. Taylor","doi":"10.1186/s12900-015-0047-z","DOIUrl":"https://doi.org/10.1186/s12900-015-0047-z","url":null,"abstract":"","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"15 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2015-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-015-0047-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4273038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crystal structure of JNK from Drosophila melanogaster reveals an evolutionarily conserved topology with that of mammalian JNK proteins","authors":"Sarin Chimnaronk,&nbsp;Jatuporn Sitthiroongruang,&nbsp;Kanokporn Srisucharitpanit,&nbsp;Monrudee Srisaisup,&nbsp;Albert J. Ketterman,&nbsp;Panadda Boonserm","doi":"10.1186/s12900-015-0045-1","DOIUrl":"https://doi.org/10.1186/s12900-015-0045-1","url":null,"abstract":"<p>The c-Jun N-terminal kinases (JNKs), members of the mitogen-activated protein kinase (MAPK) family, engage in diverse cellular responses to signals produced under normal development and stress conditions. In <i>Drosophila</i>, only one JNK member is present, whereas ten isoforms from three JNK genes (JNK1, 2, and 3) are present in mammalian cells. To date, several mammalian JNK structures have been determined, however, there has been no report of any insect JNK structure.</p><p>We report the first structure of JNK from <i>Drosophila melanogaster</i> (DJNK). The crystal structure of the unphosphorylated form of DJNK complexed with adenylyl imidodiphosphate (AMP-PNP) has been solved at 1.79?? resolution. The fold and topology of DJNK are similar to those of mammalian JNK isoforms, demonstrating their evolutionarily conserved structures and functions. Structural comparisons of DJNK and the closely related mammalian JNKs also allow identification of putative catalytic residues, substrate-binding sites and conformational alterations upon docking interaction with <i>Drosophila</i> scaffold proteins.</p><p>The DJNK structure reveals common features with those of the mammalian JNK isoforms, thereby allowing the mapping of putative catalytic and substrate binding sites. Additionally, structural changes upon peptide binding could be predicted based on the comparison with the closely-related JNK3 structure in complex with pepJIP1. This is the first structure of insect JNK reported to date, and will provide a platform for future mutational studies in <i>Drosophila</i> to ascertain the functional role of insect JNK.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"15 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2015-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-015-0045-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4664368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An intact helical domain is required for Gα14 to stimulate phospholipase Cβ","authors":"Dawna HT Kwan,&nbsp;Ka M. Wong,&nbsp;Anthony SL Chan,&nbsp;Lisa Y. Yung,&nbsp;Yung H. Wong","doi":"10.1186/s12900-015-0043-3","DOIUrl":"https://doi.org/10.1186/s12900-015-0043-3","url":null,"abstract":"<p>Stimulation of phospholipase Cβ (PLCβ) by the activated α-subunit of G_q (Gα_q) constitutes a major signaling pathway for cellular regulation, and structural studies have recently revealed the molecular interactions between PLCβ and Gα_q. Yet, most of the PLCβ-interacting residues identified on Gα_q are not unique to members of the Gα_q family. Molecular modeling predicts that the core PLCβ-interacting residues located on the switch regions of Gα_q are similarly positioned in Gα_z which does not stimulate PLCβ. Using wild-type and constitutively active chimeras constructed between Gα_z and Gα₁₄, a member of the Gα_q family, we examined if the PLCβ-interacting residues identified in Gα_q are indeed essential.</p><p>Four chimeras with the core PLCβ-interacting residues composed of Gα_z sequences were capable of binding PLCβ2 and stimulating the formation of inositol trisphosphate. Surprisingly, all chimeras with a Gα_z N-terminal half failed to functionally associate with PLCβ2, despite the fact that many of them contained the core PLCβ-interacting residues from Gα₁₄. Further analyses revealed that the non-PLCβ2 interacting chimeras were capable of interacting with other effector molecules such as adenylyl cyclase and tetratricopeptide repeat 1, indicating that they could adopt a GTP-bound active conformation.</p><p>Collectively, our study suggests that the previously identified PLCβ-interacting residues are insufficient to ensure productive interaction of Gα₁₄ with PLCβ, while an intact N-terminal half of Gα₁₄ is apparently required for PLCβ interaction.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"15 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2015-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-015-0043-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4666518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}