Intrinsically disordered proteins最新文献

{"title":"Single-molecule fluorescence studies of IDPs and IDRs","authors":"Wenwei Zheng, H. Chung","doi":"10.1016/B978-0-12-816348-1.00004-1","DOIUrl":"https://doi.org/10.1016/B978-0-12-816348-1.00004-1","url":null,"abstract":"","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85437397","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":"Perspectives on drug discovery strategies based on IDPs","authors":"Gustavo Fuertes, Laura Nevola, Santi Esteban-Martín","doi":"10.1016/B978-0-12-816348-1.00009-0","DOIUrl":"https://doi.org/10.1016/B978-0-12-816348-1.00009-0","url":null,"abstract":"","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83889481","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":"How accurate are your simulations? Effects of confined aqueous volume and AMBER FF99SB and CHARMM22/CMAP force field parameters on structural ensembles of intrinsically disordered proteins: Amyloid-β₄₂ in water.","authors":"Orkid Coskuner Weber,&nbsp;Vladimir N Uversky","doi":"10.1080/21690707.2017.1377813","DOIUrl":"https://doi.org/10.1080/21690707.2017.1377813","url":null,"abstract":"<p><p>Amyloid-β₄₂ (Aβ₄₂) is an intrinsically disordered peptide intimately related to the pathogenesis of several neurodegenerative diseases. Molecular dynamics (MD) simulations are extensively utilized in the characterization of the structures and conformational dynamics of intrinsically disordered proteins (IDPs) including Aβ₄₂, with AMBER and CHARMM parameters being commonly used in these studies. Recently, comparison of the effects of force field parameters on the Aβ₄₂ structures has started to gain significant attention. In this study, the structures of Aβ₄₂ are simulated using AMBER FF99SB and CHARMM22/CMAP parameters via replica exchange MD simulations utilizing a widely used clustering algorithm. These analyses show that the structural properties (extent and positioning of the elements of secondary and tertiary structure), radius of gyration values, number and position of salt bridges are extremely dependent on the chosen force field parameters notably with the usage of clustering algorithms. For example, predicted secondary structure elements, which are of the great importance for better understanding of the molecular mechanisms of neurodegenerative diseases, deviate enormously in models generated using currently available force field parameters for proteins. Based on the derived models, chemical shift values are calculated and compared to the experimentally determined data. This comparison revealed that although both force field parameters yield results in agreement with experiments, the obtained structural properties were rather different using a clustering algorithm. In other words, these results show that the predicted structures depend heavily on the force field parameters. Importantly, since none of the force field parameters currently utilized in MD studies were developed specifically taking into account the disordered nature of IDPs, these findings clearly indicate that new force field parameters have to be developed for IDPs considering their rapid flexibility and dynamics with high amplitude. Furthermore, molecular simulations of IDPs are typically conducted using one water volume. We show that the confined aqueous volume impacts the predicted structural properties of Aβ₄₂ in water. Although up to date, confined aqueous volume effects have been ignored in the MD simulations of IDPs in water, our data indicate that these effects have to be taken into account in predicting the structural and thermodynamic properties of disordered proteins in solution.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"5 1","pages":"e1377813"},"PeriodicalIF":0.0,"publicationDate":"2017-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2017.1377813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36519462","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":"Paradoxes and wonders of intrinsic disorder: Stability of instability.","authors":"Vladimir N Uversky","doi":"10.1080/21690707.2017.1327757","DOIUrl":"https://doi.org/10.1080/21690707.2017.1327757","url":null,"abstract":"<p><p>This article continues a series of short comments on the paradoxes and wonders of the protein intrinsic disorder phenomenon by introducing the \"stability of instability\" paradox. Intrinsically disordered proteins (IDPs) are characterized by the lack of stable 3D-structure, and, as a result, have an exceptional ability to sustain exposure to extremely harsh environmental conditions (an illustration of the \"you cannot break what is already broken\" principle). Extended IDPs are known to possess extreme thermal and acid stability and are able either to keep their functionality under these extreme conditions or to rapidly regain their functionality after returning to the normal conditions. Furthermore, sturdiness of intrinsic disorder and its capability to \"ignore\" harsh conditions provides some interesting and important advantages to its carriers, at the molecular (e.g., the cell wall-anchored accumulation-associated protein playing a crucial role in intercellular adhesion within the biofilm of <i>Staphylococcus epidermidis</i>), supramolecular (e.g., protein complexes, biologic liquid-liquid phase transitions, and proteinaceous membrane-less organelles), and organismal levels (e.g., the recently popularized case of the microscopic animals, tardigrades, or water bears, that use intrinsically disordered proteins to survive desiccation).</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"5 1","pages":"e1327757"},"PeriodicalIF":0.0,"publicationDate":"2017-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2017.1327757","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36519459","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":"Flexibility of the \"rigid\" classics or rugged bottom of the folding funnels of myoglobin, lysozyme, RNase A, chymotrypsin, cytochrome <i>c</i>, and carboxypeptidase A1.","authors":"Vladimir N Uversky","doi":"10.1080/21690707.2017.1355205","DOIUrl":"https://doi.org/10.1080/21690707.2017.1355205","url":null,"abstract":"<p><p>The abilities to crystalize of a globular protein and to solve its crystal structure seem to represent triumph of the lock-and-key model of protein functionality, where the presence of unique 3D structure resembling aperiodic crystal is considered as a prerequisite for a given protein to possess specific biologic activity. The history of protein crystallography has its roots in first crystal structures of myoglobin, lysozyme, RNase A, chymotrypsin, cytochrome <i>c</i>, and carboxypeptidase A1 solved more than 50 y ago. This article briefly considers extensive structural information currently available for these proteins and shows that the bottoms of their folding funnels (i.e., the lowest parts of their potential energy landscapes) are not smoothed but rugged. In other words, these crystallization classics are characterized by significant conformational flexibility and are not rigid (immobile) crystal-like entities.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"5 1","pages":"e1355205"},"PeriodicalIF":0.0,"publicationDate":"2017-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2017.1355205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36519460","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":"On the potential of using peculiarities of the protein intrinsic disorder distribution in mitochondrial cytochrome <i>b</i> to identify the source of animal meats.","authors":"Haitham A Yacoub, Mahmoud A Sadek, Vladimir N Uversky","doi":"10.1080/21690707.2016.1264350","DOIUrl":"10.1080/21690707.2016.1264350","url":null,"abstract":"<p><p>This study was conducted to identify the source of animal meat based on the peculiarities of protein intrinsic disorder distribution in mitochondrial cytochrome <i>b</i> (mtCyt-<i>b</i>). The analysis revealed that animal and avian species can be discriminated based on the proportions of the two groups of residues, Leu+Ile, and Ser+Pro+Ala, in the amino acid sequences of their mtCyt-<i>b</i>. Although levels of the overall intrinsic disorder in mtCyt-<i>b</i> is not very high, the peculiarities of disorder distribution within the sequences of mtCyt-<i>b</i> from different species varies in a rather specific way. In fact, positions and intensities of disorder/flexibility \"signals\" in the corresponding disorder profiles are relatively unique for avian and animal species. Therefore, it is possible to devise a set of simple rules based on the peculiarities of disorder profiles of their mtCyt-<i>b</i> proteins to discriminate among species. This intrinsic disorder-based analysis represents a new technique that could be used to provide a promising solution for identification of the source of meats.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"5 1","pages":"e1264350"},"PeriodicalIF":0.0,"publicationDate":"2017-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351768/pdf/kidp-05-01-1264350.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34845624","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":"Quarterly intrinsic disorder digest (April-May-June, 2014).","authors":"Shelly DeForte,&nbsp;Vladimir N Uversky","doi":"10.1080/21690707.2017.1287505","DOIUrl":"https://doi.org/10.1080/21690707.2017.1287505","url":null,"abstract":"<p><p>This is the 6^th issue of the Digested Disorder series that continues to use only 2 criteria for inclusion of a paper to this digest: The publication date (a paper should be published within the covered time frame) and the topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the second quarter of 2014; i.e., during the period of April, May, and June of 2014. Similar to previous issues, the papers are grouped <i>hierarchically</i> by topics they cover, and for each of the included papers a short description is given on its major findings.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"5 1","pages":"e1287505"},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2017.1287505","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34836661","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":"Understanding the roles of intrinsic disorder in subunits of hemoglobin and the disease process of sickle cell anemia.","authors":"Reis Fitzsimmons,&nbsp;Narmin Amin,&nbsp;Vladimir N Uversky","doi":"10.1080/21690707.2016.1248273","DOIUrl":"https://doi.org/10.1080/21690707.2016.1248273","url":null,"abstract":"<p><p>One of the common genetic disorders is sickle cell anemia, in which 2 recessive alleles must meet to allow for destruction and alteration in the morphology of red blood cells. This usually leads to loss of proper binding of oxygen to hemoglobin and curved, sickle-shaped erythrocytes. The mutation causing this disease occurs in the 6^th codon of the <i>HBB</i> gene encoding the hemoglobin subunit β (β-globin), a protein, serving as an integral part of the adult hemoglobin A (HbA), which is a heterotetramer of 2 α chains and 2 β chains that is responsible for binding to the oxygen in the blood. This mutation changes a charged glutamic acid to a hydrophobic valine residue and disrupts the tertiary structure and stability of the hemoglobin molecule. Since in the field of protein intrinsic disorder, charged and polar residues are typically considered as disorder promoting, in opposite to the order-promoting non-polar hydrophobic residues, in this study we attempted to answer a question if intrinsic disorder might have a role in the pathogenesis of sickle cell anemia. To this end, several disorder predictors were utilized to evaluate the presence of intrinsically disordered regions in all subunits of human hemoglobin: α, β, δ, ε, ζ, γ1, and γ2. Then, structural analysis was completed by using the SWISS-MODEL Repository to visualize the outputs of the disorder predictors. Finally, Uniprot STRING and D²P² were used to determine biochemical interactome and protein partners for each hemoglobin subunit along with analyzing their posttranslational modifications. All these properties were used to determine any differences between the 6 different types of subunits of hemoglobin and to correlate the mutation leading to sickle cell anemia with intrinsic disorder propensity.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"4 1","pages":"e1248273"},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2016.1248273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760474","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":"How disordered is my protein and what is its disorder for? A guide through the \"dark side\" of the protein universe.","authors":"Philippe Lieutaud,&nbsp;François Ferron,&nbsp;Alexey V Uversky,&nbsp;Lukasz Kurgan,&nbsp;Vladimir N Uversky,&nbsp;Sonia Longhi","doi":"10.1080/21690707.2016.1259708","DOIUrl":"https://doi.org/10.1080/21690707.2016.1259708","url":null,"abstract":"<p><p>In the last 2 decades it has become increasingly evident that a large number of proteins are either fully or partially disordered. Intrinsically disordered proteins lack a stable 3D structure, are ubiquitous and fulfill essential biological functions. Their conformational heterogeneity is encoded in their amino acid sequences, thereby allowing intrinsically disordered proteins or regions to be recognized based on properties of these sequences. The identification of disordered regions facilitates the functional annotation of proteins and is instrumental for delineating boundaries of protein domains amenable to structural determination with X-ray crystallization. This article discusses a comprehensive selection of databases and methods currently employed to disseminate experimental and putative annotations of disorder, predict disorder and identify regions involved in induced folding. It also provides a set of detailed instructions that should be followed to perform computational analysis of disorder.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"4 1","pages":"e1259708"},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2016.1259708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760477","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":"Genes encoding intrinsic disorder in Eukaryota have high GC content.","authors":"Zhenling Peng,&nbsp;Vladimir N Uversky,&nbsp;Lukasz Kurgan","doi":"10.1080/21690707.2016.1262225","DOIUrl":"https://doi.org/10.1080/21690707.2016.1262225","url":null,"abstract":"<p><p>We analyze a correlation between the GC content in genes of 12 eukaryotic species and the level of intrinsic disorder in their corresponding proteins. Comprehensive computational analysis has revealed that the disordered regions in eukaryotes are encoded by the GC-enriched gene regions and that this enrichment is correlated with the amount of disorder and is present across proteins and species characterized by varying amounts of disorder. The GC enrichment is a result of higher rate of amino acid coded by GC-rich codons in the disordered regions. Individual amino acids have the same GC-content profile between different species. Eukaryotic proteins with the disordered regions encoded by the GC-enriched gene segments carry out important biological functions including interactions with RNAs, DNAs, nucleotides, binding of calcium and metal ions, are involved in transcription, transport, cell division and certain signaling pathways, and are localized primarily in nucleus, cytosol and cytoplasm. We also investigate a possible relationship between GC content, intrinsic disorder and protein evolution. Analysis of a devised \"age\" of amino acids, their disorder-promoting capacity and the GC-enrichment of their codons suggests that the early amino acids are mostly disorder-promoting and their codons are GC-rich while most of late amino acids are mostly order-promoting.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"4 1","pages":"e1262225"},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2016.1262225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760478","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}