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991.
The hypervariable D3 domain of Salmonella flagellin, composed of residues 190-283, is situated at the outer surface of flagellar filaments. A flagellin mutant deprived of the complete D3 domain (ΔD3_FliC) exhibited a significantly decreased thermal stability (Tm 41.9 °C) as compared to intact flagellin (Tm 47.3 °C). However, the stability of filaments formed from ΔD3_FliC subunits was virtually identical with that of native flagellar filaments. While D3 comprises the most stable part of monomeric flagellin playing an important role in the stabilization of the other two (D1 and D2) domains, the situation is reversed in the polymeric state. Upon filament formation, ordering of the disordered terminal regions of flagellin in the core part of the filament results in the stabilization of the radially arranged D1 and D2 domains, and there is a substantial increase of stability even in the distant outermost D3 domain, which is connected to D2 via a pair of short antiparallel β-strands. Our experiments revealed that crosslinking the ends of the isolated D3 domain through a disulfide bridge gives rise to a stabilization effect reminiscent of that observed upon polymerization. It appears that the short interdomain linker between domains D2 and D3 serves as a stabilization center that facilitates propagation of the conformational signal from the filament core to the outer part of filament. Because D3 is a largely independent part of flagellin, its replacement by heterologous proteins or domains might offer a promising approach for creation of various fusion proteins possessing polymerization ability. 相似文献
992.
By design, structural genomics (SG) solves many structures that cannot be assigned function based on homology to known proteins. Alternative function annotation methods are therefore needed and this study focuses on function prediction with three-dimensional (3D) templates: small structural motifs built of just a few functionally critical residues. Although experimentally proven functional residues are scarce, we show here that Evolutionary Trace (ET) rankings of residue importance are sufficient to build 3D templates, match them, and then assign Gene Ontology (GO) functions in enzymes and non-enzymes alike. In a high-specificity mode, this Evolutionary Trace Annotation (ETA) method covered half (53%) of the 2384 annotated SG protein controls. Three-quarters (76%) of predictions were both correct and complete. The positive predictive value for all GO depths (all-depth PPV) was 84%, and it rose to 94% over GO depths 1-3 (depth 3 PPV). In a high-sensitivity mode, coverage rose significantly (84%), while accuracy fell moderately: 68% of predictions were both correct and complete, all-depth PPV was 75%, and depth 3 PPV was 86%. These data concur with prior mutational experiments showing that ET rank information identifies key functional determinants in proteins. In practice, ETA predicted functions in 42% of 3461 unannotated SG proteins. In 529 cases—including 280 non-enzymes and 21 for metal ion ligands—the expected accuracy is 84% at any GO depth and 94% down to GO depth 3, while for the remaining 931 the expected accuracies are 60% and 71%, respectively. Thus, local structural comparisons of evolutionarily important residues can help decipher protein functions to known reliability levels and without prior assumption on functional mechanisms. ETA is available at http://mammoth.bcm.tmc.edu/eta. 相似文献
993.
Paula V. Fernández Marina Ciancia Alicia B. Miravalles José Manuel Estevez 《Journal of phycology》2010,46(3):456-465
Cell walls in the coenocytic green seaweed Codium vermilara (Olivi) Chiaje (Bryopsidales, Chlorophyta) are composed of ~32% (w/w) β‐(1→4)‐d‐mannans, ~12% sulfated polysaccharides (SPs), and small amounts of hydroxyproline‐rich glycoprotein‐like (HRGP‐L) compounds of the arabinogalactan proteins (AGPs) and arabinosides (extensins). Similar quantities of mannans and SPs were reported previously in the related seaweed C. fragile (Suringar) Hariot. Overall, both seaweed cell walls comprise ~40%–44% of their dry weights. Within the SP group, a variety of polysaccharide structures from pyruvylated arabinogalactan sulfate and pyruvylated galactan sulfate to pyranosic arabinan sulfate are present in Codium cell walls. In this paper, the in situ distribution of the main cell‐wall polymers in the green seaweed C. vermilara was studied, comparing their arrangements with those observed in cell walls from C. fragile. The utricle cell wall in C. vermilara showed by TEM a sandwich structure of two fibrillar‐like layers of similar width delimiting a middle amorphous‐like zone. By immuno‐ and chemical imaging, the in situ distribution of β‐(1→4)‐d‐mannans and HRGP‐like epitopes was shown to consist of two distinct cell‐wall layers, whereas SPs are distributed in the middle area of the wall. The overall cell‐wall polymer arrangement of the SPs, HRGP‐like epitopes, and mannans in the utricles of C. vermilara is different from the ubiquitous green algae C. fragile, in spite of both being phylogenetically very close. In addition, a preliminary cell‐wall model of the utricle moiety is proposed for both seaweeds, C. fragile and C. vermilara. 相似文献
994.
One major problem with the existing algorithm for the prediction of protein structural classes is low accuracies for proteins from α/β and α+β classes. In this study, three novel features were rationally designed to model the differences between proteins from these two classes. In combination with other rational designed features, an 11-dimensional vector prediction method was proposed. By means of this method, the overall prediction accuracy based on 25PDB dataset was 1.5% higher than the previous best-performing method, MODAS. Furthermore, the prediction accuracy for proteins from α+β class based on 25PDB dataset was 5% higher than the previous best-performing method, SCPRED. The prediction accuracies obtained with the D675 and FC699 datasets were also improved. 相似文献
995.
Krisztian Fodor Morlin Milewski Petr Konarev Janina Wolf Ralf Erdmann Wolfgang Schliebs Young‐Hwa Song Matthias Wilmanns 《The EMBO journal》2010,29(15):2491-2500
The protein Pex19p functions as a receptor and chaperone of peroxisomal membrane proteins (PMPs). The crystal structure of the folded C‐terminal part of the receptor reveals a globular domain that displays a bundle of three long helices in an antiparallel arrangement. Complementary functional experiments, using a range of truncated Pex19p constructs, show that the structured α‐helical domain binds PMP‐targeting signal (mPTS) sequences with about 10 μM affinity. Removal of a conserved N‐terminal helical segment from the mPTS recognition domain impairs the ability for mPTS binding, indicating that it forms part of the mPTS‐binding site. Pex19p variants with mutations in the same sequence segment abolish correct cargo import. Our data indicate a divided N‐terminal and C‐terminal structural arrangement in Pex19p, which is reminiscent of a similar division in the Pex5p receptor, to allow separation of cargo‐targeting signal recognition and additional functions. 相似文献
996.
Natasja Brooijmans Yu‐Wei Chang Dominick Mobilio Rajiah A. Denny Christine Humblet 《Protein science : a publication of the Protein Society》2010,19(4):763-774
The development of a kinase structural database, the kinase knowledge base (KKB), is described. It covers all human kinase domain structures that have been deposited in the Protein Data Bank. All structures are renumbered using a common scheme, which enables efficient cross‐comparisons and multiple queries of interest to the kinase field. The common numbering scheme is also used to automatically annotate conserved residues and motifs, and conformationally classify the structures based on the DFG‐loop and Helix C. Analyses of residue conservation in the ATP binding site using the full human‐kinome–sequence alignment lead to the identification of a conserved hydrogen bond between the hinge region backbone and a glycine in the specificity surface. Furthermore, 90% of kinases are found to have at least one stabilizing interaction for the hinge region, which has not been described before. 相似文献
997.
William Burkitt Paula Domann Gavin O'Connor 《Protein science : a publication of the Protein Society》2010,19(4):826-835
Oxidation of methionine residues in biopharmaceuticals is a common and often unwanted modification that frequently occurs during their manufacture and storage. It often results in a lack of stability and biological function of the product, necessitating continuous testing for the modification throughout the product shelf life. A major class of biopharmaceutical products are monoclonal antibodies (mAbs), however, techniques for their detailed structural analysis have until recently been limited. Hydrogen/deuterium exchange mass spectrometry (HXMS) has recently been successfully applied to the analysis of mAbs. Here we used HXMS to identify and localise the structural changes that occurred in a mAb (IgG1) after accelerated oxidative stress. Structural alterations in a number of segments of the Fc region were observed and these related to oxidation of methionine residues. These included a large change in the hydrogen exchange profile of residues 247–253 of the heavy chain, while smaller changes in hydrogen exchange profile were identified for peptides that contained residues in the interface of the CH2 and CH3 domains. 相似文献
998.
999.
在后基因组时代,随着大量物种全基因组序列的获得,结构生物学家面临着结构基因组学的新机遇和挑战。与传统的结构生物学不同的是,结构基因组学的研究主要集中在结构和功能未知并且与从前研究的蛋白质相似性很小的蛋白质。准确的来讲,结构基因组学通过高通量蛋白质表达、结构解析来完成所有蛋白质家族的结构表征,从而能够通过结构预测功能。加州结构基因组学联合实验室发展了高度自动化的蛋白质合成、结晶、结构解析生产线。然而由于一些蛋白质不能被结晶,要想覆盖所有蛋白质结构域还有很大困难。Wuthrich的研究小组通过一些高通量的目的蛋白质筛选和NMR结构解析的方法解决了这一难题。与X射线晶体学解析蛋白质结构相比,NMR技术由于能够解析更接近生理状态的溶液结构而具有互补性。通过获得溶液中的蛋白质稳定性、动力学特征和相互作用信息,正如在朊蛋白和SARS相关蛋白的研究中所表现的那样,NMR技术从扩大已知的蛋白质结构数据库、新的蛋白质功能到化学生物学研究中都扮演着激动人心的角色。 相似文献
1000.