BMC Structural Biology最新文献

{"title":"Annual acknowledgement of manuscript reviewers","authors":"Simon Harold","doi":"10.1186/1472-6807-13-1","DOIUrl":"https://doi.org/10.1186/1472-6807-13-1","url":null,"abstract":"","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2013-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4744937","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":"Evolutionarily consistent families in SCOP: sequence, structure and function","authors":"Ralph B Pethica,&nbsp;Michael Levitt,&nbsp;Julian Gough","doi":"10.1186/1472-6807-12-27","DOIUrl":"https://doi.org/10.1186/1472-6807-12-27","url":null,"abstract":"<p>SCOP is a hierarchical domain classification system for proteins of known structure. The superfamily level has a clear definition: Protein domains belong to the same superfamily if there is structural, functional and sequence evidence for a common evolutionary ancestor. Superfamilies are sub-classified into families, however, there is not such a clear basis for the family level groupings. Do SCOP families group together domains with sequence similarity, do they group domains with similar structure or by common function? It is these questions we answer, but most importantly, whether each family represents a distinct phylogenetic group within a superfamily.</p><p>Several phylogenetic trees were generated for each superfamily: one derived from a multiple sequence alignment, one based on structural distances, and the final two from presence/absence of GO terms or EC numbers assigned to domains. The topologies of the resulting trees and confidence values were compared to the SCOP family classification.</p><p>We show that SCOP family groupings are evolutionarily consistent to a very high degree with respect to classical sequence phylogenetics. The trees built from (automatically generated) structural distances correlate well, but are not always consistent with SCOP (hand annotated) groupings. Trees derived from functional data are less consistent with the family level than those from structure or sequence, though the majority still agree. Much of GO and EC annotation applies directly to one family or subset of the family; relatively few terms apply at the superfamily level. Maximum sequence diversity within a family is on average 22% but close to zero for superfamilies.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-27","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4732915","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 of HutZ, a heme storage protein from Vibrio cholerae: A structural mismatch observed in the region of high sequence conservation","authors":"Xiuhua Liu,&nbsp;Jing Gong,&nbsp;Tiandi Wei,&nbsp;Zhi Wang,&nbsp;Qian Du,&nbsp;Deyu Zhu,&nbsp;Yan Huang,&nbsp;Sujuan Xu,&nbsp;Lichuan Gu","doi":"10.1186/1472-6807-12-23","DOIUrl":"https://doi.org/10.1186/1472-6807-12-23","url":null,"abstract":"<p>HutZ is the sole heme storage protein identified in the pathogenic bacterium <i>Vibrio cholerae</i> and is required for optimal heme utilization. However, no heme oxygenase activity has been observed with this protein. Thus far, HutZ’s structure and heme-binding mechanism are unknown.</p><p>We report the first crystal structure of HutZ in a homodimer determined at 2.0 ? resolution. The HutZ structure adopted a typical split-barrel fold. Through a docking study and site-directed mutagenesis, a heme-binding model for the HutZ dimer is proposed. Very interestingly, structural superimposition of HutZ and its homologous protein HugZ, a heme oxygenase from <i>Helicobacter pylori</i>, exhibited a structural mismatch of one amino acid residue in β6 of HutZ, although residues involved in this region are highly conserved in both proteins. Derived homologous models of different single point variants with model evaluations suggested that Pro¹⁴⁰ of HutZ, corresponding to Phe²¹⁵ of HugZ, might have been the main contributor to the structural mismatch. This mismatch initiates more divergent structural characteristics towards their C-terminal regions, which are essential features for the heme-binding of HugZ as a heme oxygenase.</p><p>HutZ’s deficiency in heme oxygenase activity might derive from its residue shift relative to the heme oxygenase HugZ. This residue shift also emphasized a limitation of the traditional template selection criterion for homology modeling.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-23","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5021826","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":"Enabling structure-based drug design of Tyk2 through co-crystallization with a stabilizing aminoindazole inhibitor","authors":"Maria A Argiriadi,&nbsp;Eric R Goedken,&nbsp;David Banach,&nbsp;David W Borhani,&nbsp;Andrew Burchat,&nbsp;Richard W Dixon,&nbsp;Doug Marcotte,&nbsp;Gary Overmeyer,&nbsp;Valerie Pivorunas,&nbsp;Ramkrishna Sadhukhan,&nbsp;Silvino Sousa,&nbsp;Nigel St John Moore,&nbsp;Medha Tomlinson,&nbsp;Jeffrey Voss,&nbsp;Lu Wang,&nbsp;Neil Wishart,&nbsp;Kevin Woller,&nbsp;Robert V Talanian","doi":"10.1186/1472-6807-12-22","DOIUrl":"https://doi.org/10.1186/1472-6807-12-22","url":null,"abstract":"<p>Structure-based drug design (SBDD) can accelerate inhibitor lead design and optimization, and efficient methods including protein purification, characterization, crystallization, and high-resolution diffraction are all needed for rapid, iterative structure determination. Janus kinases are important targets that are amenable to structure-based drug design. Here we present the first mouse Tyk2 crystal structures, which are complexed to 3-aminoindazole compounds.</p><p>A comprehensive construct design effort included <i>N</i>- and <i>C</i>-terminal variations, kinase-inactive mutations, and multiple species orthologs. High-throughput cloning and expression methods were coupled with an abbreviated purification protocol to optimize protein solubility and stability. In total, 50 Tyk2 constructs were generated. Many displayed poor expression, inadequate solubility, or incomplete affinity tag processing. One kinase-inactive murine Tyk2 construct, complexed with an ATP-competitive 3-aminoindazole inhibitor, provided crystals that diffracted to 2.5–2.6 ? resolution. This structure revealed initial “hot-spot” regions for SBDD, and provided a robust platform for ligand soaking experiments. Compared to previously reported human Tyk2 inhibitor crystal structures (Chrencik <i>et al.</i> (2010) <i>J Mol Biol</i> 400:413), our structures revealed a key difference in the glycine-rich loop conformation that is induced by the inhibitor. Ligand binding also conferred resistance to proteolytic degradation by thermolysin. As crystals could not be obtained with the unliganded enzyme, this enhanced stability is likely important for successful crystallization and inhibitor soaking methods.</p><p>Practical criteria for construct performance and prioritization, the optimization of purification protocols to enhance protein yields and stability, and use of high-throughput construct exploration enable structure determination methods early in the drug discovery process. Additionally, specific ligands stabilize Tyk2 protein and may thereby enable crystallization.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-22","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4805793","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":"Exploring the binding of BACE-1 inhibitors using comparative binding energy analysis (COMBINE)","authors":"Shu Liu,&nbsp;Rao Fu,&nbsp;Xiao Cheng,&nbsp;Sheng-Ping Chen,&nbsp;Li-Hua Zhou","doi":"10.1186/1472-6807-12-21","DOIUrl":"https://doi.org/10.1186/1472-6807-12-21","url":null,"abstract":"<p>The inhibition of the activity of β-secretase (BACE-1) is a potentially important approach for the treatment of Alzheimer disease. To explore the mechanism of inhibition, we describe the use of 46 X-ray crystallographic BACE-1/inhibitor complexes to derive quantitative structure-activity relationship (QSAR) models. The inhibitors were aligned by superimposing 46 X-ray crystallographic BACE-1/inhibitor complexes, and gCOMBINE software was used to perform COMparative BINding Energy (COMBINE) analysis on these 46 minimized BACE-1/inhibitor complexes<b>.</b> The major advantage of the COMBINE analysis is that it can quantitatively extract key residues involved in binding the ligand and identify the nature of the interactions between the ligand and receptor.</p><p>By considering the contributions of the protein residues to the electrostatic and van der Waals intermolecular interaction energies, two predictive and robust COMBINE models were developed: (i) the 3-PC distance-dependent dielectric constant model (built from a single X-ray crystal structure) with a q² value of 0.74 and an SDEC value of 0.521; and (ii) the 5-PC sigmoidal electrostatic model (built from the actual complexes present in the Brookhaven Protein Data Bank) with a q² value of 0.79 and an SDEC value of 0.41.</p><p>These QSAR models and the information describing the inhibition provide useful insights into the design of novel inhibitors via the optimization of the interactions between ligands and those key residues of BACE-1.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-21","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5031027","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":"A three-dimensional topology of complex I inferred from evolutionary correlations","authors":"Philip R Kensche,&nbsp;Isabel Duarte,&nbsp;Martijn A Huynen","doi":"10.1186/1472-6807-12-19","DOIUrl":"https://doi.org/10.1186/1472-6807-12-19","url":null,"abstract":"<p>The quaternary structure of eukaryotic NADH:ubiquinone oxidoreductase (complex I), the largest complex of the oxidative phosphorylation, is still mostly unresolved. Furthermore, it is unknown where transiently bound assembly factors interact with complex I. We therefore asked whether the evolution of complex I contains information about its 3D topology and the binding positions of its assembly factors. We approached these questions by correlating the evolutionary rates of eukaryotic complex I subunits using the mirror-tree method and mapping the results into a 3D representation by multidimensional scaling.</p><p>More than 60% of the evolutionary correlation among the conserved seven subunits of the complex I matrix arm can be explained by the physical distance between the subunits. The three-dimensional evolutionary model of the eukaryotic conserved matrix arm has a striking similarity to the matrix arm quaternary structure in the bacterium <i>Thermus thermophilus</i> (rmsd=19 ?) and supports the previous finding that in eukaryotes the N-module is turned relative to the Q-module when compared to bacteria. By contrast, the evolutionary rates contained little information about the structure of the membrane arm. A large evolutionary model of 45 subunits and assembly factors allows to predict subunit positions and interactions (rmsd = 52.6 ?). The model supports an interaction of NDUFAF3, C8orf38 and C2orf56 during the assembly of the proximal matrix arm and the membrane arm. The model further suggests a tight relationship between the assembly factor NUBPL and NDUFA2, which both have been linked to iron-sulfur cluster assembly, as well as between NDUFA12 and its paralog, the assembly factor NDUFAF2.</p><p>The physical distance between subunits of complex I is a major correlate of the rate of protein evolution in the complex I matrix arm and is sufficient to infer parts of the complex’s structure with high accuracy. The resulting evolutionary model predicts the positions of a number of subunits and assembly factors.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-19","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4109049","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":"Dependence of α-helical and β-sheet amino acid propensities on the overall protein fold type","authors":"Kazuo Fujiwara,&nbsp;Hiromi Toda,&nbsp;Masamichi Ikeguchi","doi":"10.1186/1472-6807-12-18","DOIUrl":"https://doi.org/10.1186/1472-6807-12-18","url":null,"abstract":"<p>A large number of studies have been carried out to obtain amino acid propensities for α-helices and β-sheets. The obtained propensities for α-helices are consistent with each other, and the pair-wise correlation coefficient is frequently high. On the other hand, the β-sheet propensities obtained by several studies differed significantly, indicating that the context significantly affects β-sheet propensity.</p><p>We calculated amino acid propensities for α-helices and β-sheets for 39 and 24 protein folds, respectively, and addressed whether they correlate with the fold. The propensities were also calculated for exposed and buried sites, respectively. Results showed that α-helix propensities do not differ significantly by fold, but β-sheet propensities are diverse and depend on the fold. The propensities calculated for exposed sites and buried sites are similar for α-helix, but such is not the case for the β-sheet propensities. We also found some fold dependence on amino acid frequency in β-strands. Folds with a high Ser, Thr and Asn content at exposed sites in β-strands tend to have a low Leu, Ile, Glu, Lys and Arg content (correlation coefficient = ?0.90) and to have flat β-sheets. At buried sites in β-strands, the content of Tyr, Trp, Gln and Ser correlates negatively with the content of Val, Ile and Leu (correlation coefficient = ?0.93). \"All-β\" proteins tend to have a higher content of Tyr, Trp, Gln and Ser, whereas \"α/β\" proteins tend to have a higher content of Val, Ile and Leu.</p><p>The α-helix propensities are similar for all folds and for exposed and buried residues. However, β-sheet propensities calculated for exposed residues differ from those for buried residues, indicating that the exposed-residue fraction is one of the major factors governing amino acid composition in β-strands. Furthermore, the correlations we detected suggest that amino acid composition is related to folding properties such as the twist of a β-strand or association between two β sheets.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4066164","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":"Structural characterization of S100A15 reveals a novel zinc coordination site among S100 proteins and altered surface chemistry with functional implications for receptor binding","authors":"Jill I Murray,&nbsp;Michelle L Tonkin,&nbsp;Amanda L Whiting,&nbsp;Fangni Peng,&nbsp;Benjamin Farnell,&nbsp;Jay T Cullen,&nbsp;Fraser Hof,&nbsp;Martin J Boulanger","doi":"10.1186/1472-6807-12-16","DOIUrl":"https://doi.org/10.1186/1472-6807-12-16","url":null,"abstract":"<p>S100 proteins are a family of small, EF-hand containing calcium-binding signaling proteins that are implicated in many cancers. While the majority of human S100 proteins share 25-65% sequence similarity, S100A7 and its recently identified paralog, S100A15, display 93% sequence identity. Intriguingly, however, S100A7 and S100A15 serve distinct roles in inflammatory skin disease; S100A7 signals through the receptor for advanced glycation products (RAGE) in a zinc-dependent manner, while S100A15 signals through a yet unidentified G-protein coupled receptor in a zinc-independent manner. Of the seven divergent residues that differentiate S100A7 and S100A15, four cluster in a zinc-binding region and the remaining three localize to a predicted receptor-binding surface.</p><p>To investigate the structural and functional consequences of these divergent clusters, we report the X-ray crystal structures of S100A15 and S100A7D24G, a hybrid variant where the zinc ligand Asp24 of S100A7 has been substituted with the glycine of S100A15, to 1.7?? and 1.6?? resolution, respectively. Remarkably, despite replacement of the Asp ligand, zinc binding is retained at the S100A15 dimer interface with distorted tetrahedral geometry and a chloride ion serving as an exogenous fourth ligand. Zinc binding was confirmed using anomalous difference maps and solution binding studies that revealed similar affinities of zinc for S100A15 and S100A7. Additionally, the predicted receptor-binding surface on S100A7 is substantially more basic in S100A15 without incurring structural rearrangement.</p><p>Here we demonstrate that S100A15 retains the ability to coordinate zinc through incorporation of an exogenous ligand resulting in a unique zinc-binding site among S100 proteins. The altered surface chemistry between S100A7 and S100A15 that localizes to the predicted receptor binding site is likely responsible for the differential recognition of distinct protein targets. Collectively, these data provide novel insight into the structural and functional consequences of the divergent surfaces between S100A7 and S100A15 that may be exploited for targeted therapies.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4085632","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":"Structure of human aspartyl aminopeptidase complexed with substrate analogue: insight into catalytic mechanism, substrate specificity and M18 peptidase family","authors":"Apirat Chaikuad,&nbsp;Ewa S Pilka,&nbsp;Antonio De Riso,&nbsp;Frank von Delft,&nbsp;Kathryn L Kavanagh,&nbsp;Catherine Vénien-Bryan,&nbsp;Udo Oppermann,&nbsp;Wyatt W Yue","doi":"10.1186/1472-6807-12-14","DOIUrl":"https://doi.org/10.1186/1472-6807-12-14","url":null,"abstract":"<p>Aspartyl aminopeptidase (DNPEP), with specificity towards an acidic amino acid at the N-terminus, is the only mammalian member among the poorly understood M18 peptidases. DNPEP has implicated roles in protein and peptide metabolism, as well as the renin-angiotensin system in blood pressure regulation. Despite previous enzyme and substrate characterization, structural details of DNPEP regarding ligand recognition and catalytic mechanism remain to be delineated.</p><p>The crystal structure of human DNPEP complexed with zinc and a substrate analogue aspartate-β-hydroxamate reveals a dodecameric machinery built by domain-swapped dimers, in agreement with electron microscopy data. A structural comparison with bacterial homologues identifies unifying catalytic features among the poorly understood M18 enzymes. The bound ligands in the active site also reveal the coordination mode of the binuclear zinc centre and a substrate specificity pocket for acidic amino acids.</p><p>The DNPEP structure provides a molecular framework to understand its catalysis that is mediated by active site loop swapping, a mechanism likely adopted in other M18 and M42 metallopeptidases that form dodecameric complexes as a self-compartmentalization strategy. Small differences in the substrate binding pocket such as shape and positive charges, the latter conferred by a basic lysine residue, further provide the key to distinguishing substrate preference. Together, the structural knowledge will aid in the development of enzyme-/family-specific aminopeptidase inhibitors.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4828813","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":"Crystal structure of the Yersinia enterocolitica type III secretion chaperone SycD in complex with a peptide of the minor translocator YopD","authors":"Madeleine Schreiner,&nbsp;Hartmut H Niemann","doi":"10.1186/1472-6807-12-13","DOIUrl":"https://doi.org/10.1186/1472-6807-12-13","url":null,"abstract":"<p>Type III secretion systems are used by Gram-negative bacteria as “macromolecular syringes” to inject effector proteins into eukaryotic cells. Two hydrophobic proteins called translocators form the necessary pore in the host cell membrane. Both translocators depend on binding to a single chaperone in the bacterial cytoplasm to ensure their stability and efficient transport through the secretion needle. It was suggested that the conserved chaperones bind the more divergent translocators via a hexapeptide motif that is found in both translocators and conserved between species.</p><p>We crystallized a synthetic decapeptide from the <i>Yersinia enterocolitica</i> minor type III secretion translocator YopD bound to its cognate chaperone SycD and determined the complex structure at 2.5?? resolution. The structure of peptide-bound SycD is almost identical to that of apo SycD with an all helical fold consisting of three tetratricopeptide repeats (TPRs) and an additional C-terminal helix. Peptide-bound SycD formed a kinked head-to-head dimer that had previously been observed for the apo form of SycD. The homodimer interface comprises both helices of the first tetratricopeptide repeat. The YopD peptide bound in extended conformation into a mainly hydrophobic groove on the concave side of SycD. TPRs 1 and 2 of SycD form three hydrophobic pockets that accommodated the conserved hydrophobic residues at position 1, 3 and 6 of the translocator hexapeptide sequence. Two tyrosines that are highly conserved among translocator chaperones contribute to the hydrophobic patches but also form hydrogen bonds to the peptide backbone.</p><p>The interaction between SycD and YopD is very similar to the binding of the <i>Pseudomonas</i> minor translocator PopD to its chaperone PcrH and the <i>Shigella</i> major translocator IpaB to its chaperone IpgC. This confirms the prediction made by Kolbe and co-workers that a hexapeptide with hydrophobic residues at three positions is a conserved chaperone binding motif. Because the hydrophobic groove on the concave side of translocator chaperones is involved in binding of the major and the minor translocator, simultaneous binding of both translocators to a single type III secretion class II chaperone appears unlikely.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4723847","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}