Intrinsically disordered proteins最新文献

{"title":"Comparison of the intrinsic disorder propensities of the RuBisCO activase enzyme from the motile and non-motile oceanic green microalgae.","authors":"Lucia Sena, Vladimir N Uversky","doi":"10.1080/21690707.2016.1253526","DOIUrl":"10.1080/21690707.2016.1253526","url":null,"abstract":"<p><p>Green oceanic microalgae are efficient converters of solar energy into the biomass via the photosynthesis process, with the first step of carbon fixation in the photosynthesis being controlled by the enzyme ribulose-1, 5-bisphosphate carboxylase/oxygenase (RuBisCO), which is a large proteinaceous machine composed of large (L, 52 kDa) and small (S, 12 kDa) subunits arranged as a L₈S₈ hexadecamer that catalyzes the formation of 2 phosphoglyceric acid molecules from one ribulose 1,5-bisphosphate (RuBP) molecule and one of carbon dioxide (CO₂) and that is considered as the most abundant protein on Earth. The catalytic efficiency of this protein is controlled by the RuBisCO activase (RCA) that interacts with RuBisCO and promotes the CO₂ entrance to the active site of RuBisCO by removing RuBP. One of the peculiar features of RCA is the presence of functional disordered tails that might play a role in RCA-RuBisCO interaction. Based on their ability to move, microalgae are grouped into 2 major class, motile and non-motile. Motile microalgae have an obvious advantage over their non-motile counterparts because of their ability to actively migrate within the water column to find the most optimal environmental conditions. We hypothesizes that the RCA could be functionally different in the non-motile and motile microalgae. To check this hypothesis, we conducted a comparative computational analysis of the RCAs from the representatives of the non-motile (<i>Ostreococcus tauri</i>) and motile (<i>Tetraselmis</i> sp. GSL018) green oceanic microalgae.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"4 1","pages":"e1253526"},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314929/pdf/kidp-04-01-1253526.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760475","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":"Intrinsic disorder in spondins and some of their interacting partners.","authors":"Oluwole Alowolodu,&nbsp;Gbemisola Johnson,&nbsp;Lamis Alashwal,&nbsp;Iqbal Addou,&nbsp;Irina V Zhdanova,&nbsp;Vladimir N Uversky","doi":"10.1080/21690707.2016.1255295","DOIUrl":"https://doi.org/10.1080/21690707.2016.1255295","url":null,"abstract":"<p><p>Spondins, which are proteins that inhibit and promote adherence of embryonic cells so as to aid axonal growth are part of the thrombospondin-1 family. Spondins function in several important biological processes, such as apoptosis, angiogenesis, etc. Spondins constitute a thrombospondin subfamily that includes F-spondin, a protein that interacts with Aβ precursor protein and inhibits its proteolytic processing; R-spondin, a 4-membered group of proteins that regulates Wnt pathway and have other functions, such as regulation of kidney proliferation, induction of epithelial proliferation, the tumor suppressant action; M-spondin that mediates mechanical linkage between the muscles and apodemes; and the SCO-spondin, a protein important for neuronal development. In this study, we investigated intrinsic disorder status of human spondins and their interacting partners, such as members of the LRP family, LGR family, Frizzled family, and several other binding partners in order to establish the existence and importance of disordered regions in spondins and their interacting partners by conducting a detailed analysis of their sequences, finding disordered regions, and establishing a correlation between their structure and biological functions.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"4 1","pages":"e1255295"},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2016.1255295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760476","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":"Intrinsic disorder in biomarkers of insulin resistance, hypoadiponectinemia, and endothelial dysfunction among the type 2 diabetic patients.","authors":"Osama H Al-Jiffri,&nbsp;Fadwa M Al-Sharif,&nbsp;Essam H Al-Jiffri,&nbsp;Vladimir N Uversky","doi":"10.1080/21690707.2016.1171278","DOIUrl":"https://doi.org/10.1080/21690707.2016.1171278","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with various complications including cardiovascular diseases and related mortality. The present study aimed to analyze the abundance and functionality of intrinsically disordered regions in several biomarkers of insulin resistance, adiponectin, and endothelial dysfunction found in the T2DM patients. In fact, in comparison to controls, obese T2DM patients are known to have significantly higher levels of inter-cellular adhesion molecule (iCAM-1), vascular cell adhesion molecule (vCAM-1), and E-selectin, whereas their adiponectin levels are relatively low. Bioinformatics analysis revealed that these selected biomarkers (iCAM-1, vCAM-1, E-selectin, and adiponectin) are characterized by the noticeable levels of intrinsic disorder propensity and high binding promiscuity, which are important features expected for proteins serving as biomarkers. Within the limit of studied groups, there is an association between insulin resistance and both hypoadiponectinemia and endothelial dysfunction.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"4 1","pages":"e1171278"},"PeriodicalIF":0.0,"publicationDate":"2016-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2016.1171278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760473","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":"Are the curli proteins CsgE and CsgF intrinsically disordered?","authors":"Amanda Green,&nbsp;Nguyen Pham,&nbsp;Krystle Osby,&nbsp;Alexander Aram,&nbsp;Rochelle Claudius,&nbsp;Sharon Patray,&nbsp;Sajith A Jayasinghe","doi":"10.1080/21690707.2015.1130675","DOIUrl":"https://doi.org/10.1080/21690707.2015.1130675","url":null,"abstract":"<p><p>Curli are a type of proteinaceous cell surface filament produced by enteric bacteria such as <i>Escherichia</i> and <i>Salmonella</i> that facilitate cell adhesion and invasion, bio-film formation, and environmental persistence. Curli assembly involves 6 proteins encoded by the curli specific genes A, B, C, E, F, and G. Although CsgA is the major structural component of curli, CsgE, and CsgF, are thought to play important chaperone like functions in the assembly of CsgA into curli. Given that some proteins with chaperone like function have been observed to contain disordered regions, sequence analysis and circular dichroism spectroscopy was used to investigate the possibility that structures of CsgE and CsgF were also disordered. Sequence analysis based on charge and hydrophobicity, as well as using the disorder prediction software PONDR, indicates that both proteins have significant regions of disorder. The secondary structure and unfolding, of CsgE and CsgF, analyzed using circular dichroism spectroscopy suggests that both proteins lack a well defined and stable structure. These observations support the hypothesis that the curli assembly proteins CsgE and CsgF are disordered proteins containing intrinsically disordered regions.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"4 1","pages":"e1130675"},"PeriodicalIF":0.0,"publicationDate":"2016-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2015.1130675","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760036","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 (January-February-March, 2014).","authors":"Shelly DeForte,&nbsp;Krishna D Reddy,&nbsp;Vladimir N Uversky","doi":"10.1080/21690707.2016.1153395","DOIUrl":"https://doi.org/10.1080/21690707.2016.1153395","url":null,"abstract":"<p><p>This is the 5^th issue of the Digested Disorder series that represents a reader's digest of the scientific literature on intrinsically disordered proteins. We continue 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 first quarter of 2014; i.e., during the period of January, February, and March of 2014. Similar to previous issues, the papers are grouped hierarchically 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":"4 1","pages":"e1153395"},"PeriodicalIF":0.0,"publicationDate":"2016-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2016.1153395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760472","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: Complexity of simplicity.","authors":"Vladimir N Uversky","doi":"10.1080/21690707.2015.1135015","DOIUrl":"https://doi.org/10.1080/21690707.2015.1135015","url":null,"abstract":"<p><p>At first glance it may seem that intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are simpler than ordered proteins and domains on multiple levels. However, such multilevel simplicity equips these proteins with the ability to have very complex behavior.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"4 1","pages":"e1135015"},"PeriodicalIF":0.0,"publicationDate":"2016-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2015.1135015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760037","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":"Missing strings of residues in protein crystal structures.","authors":"Kristina Djinovic-Carugo,&nbsp;Oliviero Carugo","doi":"10.1080/21690707.2015.1095697","DOIUrl":"https://doi.org/10.1080/21690707.2015.1095697","url":null,"abstract":"<p><p>A large fraction of the protein crystal structures deposited in the Protein Data Bank are incomplete, since the position of one or more residues is not reported, despite these residues are part of the material that was analyzed. This may bias the use of the protein crystal structures by molecular biologists. Here we observe that in the large majority of the protein crystal structures strings of residues are missing. Polar residues incline to occur in missing strings together with glycine, while apolar and aromatic residues tend to avoid them. Particularly flexible residues, as shown by their extremely high B-factors, by their exposure to the solvent and by their secondary structures, flank the missing strings. These data should be a helpful guideline for crystallographers that encounter regions of flat and uninterpretable electron density as well as end-users of crystal structures.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"3 1","pages":"e1095697"},"PeriodicalIF":0.0,"publicationDate":"2015-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2015.1095697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760035","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":"Formation of covalent di-tyrosine dimers in recombinant α-synuclein.","authors":"A van Maarschalkerweerd,&nbsp;M N Pedersen,&nbsp;H Peterson,&nbsp;M Nilsson,&nbsp;Ttt Nguyen,&nbsp;T Skamris,&nbsp;K Rand,&nbsp;V Vetri,&nbsp;A E Langkilde,&nbsp;B Vestergaard","doi":"10.1080/21690707.2015.1071302","DOIUrl":"https://doi.org/10.1080/21690707.2015.1071302","url":null,"abstract":"<p><p>Parkinson's disease is associated with fibril deposition in the diseased brain. Misfolding events of the intrinsically disordered synaptic protein α-synuclein are suggested to lead to the formation of transient oligomeric and cytotoxic species. The etiology of Parkinson's disease is further associated with mitochondrial dysfunction and formation of reactive oxygen species. Oxidative stress causes chemical modification of native α-synuclein, plausibly further influencing misfolding events. Here, we present evidence for the spontaneous formation of covalent di-tyrosine α-synuclein dimers in standard recombinant protein preparations, induced without extrinsic oxidative or nitrative agents. The dimers exhibit no secondary structure but advanced SAXS studies reveal an increased structural definition, resulting in a more hydrophobic micro-environment than the highly disordered monomer. Accordingly, monomers and dimers follow distinct fibrillation pathways.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"3 1","pages":"e1071302"},"PeriodicalIF":0.0,"publicationDate":"2015-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2015.1071302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760034","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: Prevalence of exceptionality.","authors":"Vladimir N Uversky","doi":"10.1080/21690707.2015.1065029","DOIUrl":"https://doi.org/10.1080/21690707.2015.1065029","url":null,"abstract":"This article opens a series of short comments on paradoxes and wonders of the protein intrinsic disorder phenomenon. Here, the “prevalence of exceptionality” paradox is introduced in a form of a brief historical overview that shows a progression in understanding of the natural abundance of intrinsically disordered proteins from the early days, when these biologically active proteins without unique structures were taken as rare exceptions, to the current days, when the prevalence of intrinsically disordered proteins (IDPs) in various proteomes and biological processes is a well-recognized reality. In one of the first systematic works on IDPs published in 1997, Dunker et al. searched PDB for proteins containing at least one intrinsically disordered region (IDR) longer than seven 7 residues. There, IDRs were defined as regions of missing electron density in the corresponding crystal structures (since disorder leads to incoherent X-ray scattering and subsequent absence of electron density in the solved structure), and, depending on their length, were partitioned into short, medium and long data sets, denoted as SIDR (7–21 amino acids), MIDR (22–44 amino acids), and LIDR (45 or more amino acids), respectively. The SIDR dataset contained 38 disordered segments from 34 proteins with 411 disordered amino acids and 11,050 total amino acids; MIDR set contained 22 disordered segments from 20 proteins with 464 disordered amino acids and 4,764 total amino acids; and LIDR set contained 7 regions from 7 proteins with 465 disordered amino acids and 2,069 total amino acids. In the subsequent study, the set of seven 7 LIDR proteins with the X-rayX-ray-characterized regions of disorder was extended to include seven 7 proteins shown to be disordered by NMR, with the total number of disordered residues in that set being 677 amino acids. Uversky et al. compiled a list of 91 IDPs characterized by NMR, circular dichroism or other biophysical techniques. Proteins in that study were completely disordered, belonging to the sub-class of natively unfolded proteins that do not have any (or almost any) residual structure. Those IDPs ranged in length from 49 to 1,827 residues and the total number of disordered residues in that set was 17,318 amino acids. In 2001, it has been reported that the list of experimentally validated IDPs characterized by NMR or X-ray, or circular dichroism can be extended to 150 entries that contained 17,417 disordered residues and a year later, this set was further extended to total 157 proteins with 18,833 disordered residues A subsequent search of X-rayX-ray crystal structures and the literature have further expanded this list to more than 200 proteins that contain disordered regions of 30 consecutive residues or longer as characterized by X-ray crystallography, proteolytic digestion or other physical analyses such as NMR or circular dichroism. Recently, the exhaustive literature analysis revealed that the current list of experimentally validated ID","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"3 1","pages":"e1065029"},"PeriodicalIF":0.0,"publicationDate":"2015-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2015.1065029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760032","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":"Collapsed state of polyglutamic acid results in amyloid spherulite formation.","authors":"Daniel Stehli,&nbsp;Mentor Mulaj,&nbsp;Tatiana Miti,&nbsp;Joshua Traina,&nbsp;Joseph Foley,&nbsp;Martin Muschol","doi":"10.1080/21690707.2015.1056905","DOIUrl":"https://doi.org/10.1080/21690707.2015.1056905","url":null,"abstract":"<p><p>Self-assembly of proteins and peptides into amyloid fibrils involves multiple distinct intermediates and late-stage fibrillar polymorphs. Understanding the conditions and mechanisms that promote the formation of one type of intermediate and polymorph over the other represents a fundamental challenge. Answers to this question are also of immediate biomedical relevance since different amyloid aggregate species have been shown to have distinct pathogenic potencies. One amyloid polymorph that has received comparatively little attention are amyloid spherulites. Here we report that self-assembly of the intrinsically disordered polymer poly(L-glutamic) acid (PLE) can generate amyloid spherulites. We characterize spherulite growth kinetics, as well as the morphological, optical and tinctorial features of this amyloid polymorph previously unreported for PLE. We find that PLE spherulites share both tinctorial and structural characteristics with their amyloid fibril counterparts. Differences in PLE's molecular weight, polydispersity or chemistry could not explain the selective propensity toward either fibril or spherulite formation. Instead, we provide evidence that PLE polymers can exist in either a collapsed globule or an extended random coil conformation. The collapsed globule consistently produces spherulites while the extended coil assembles into disordered fibril bundles. This results suggests that these 2 PLE conformers directly affect the morphology of the resulting macroscopic amyloid assembly.</p>","PeriodicalId":90188,"journal":{"name":"Intrinsically disordered proteins","volume":"3 1","pages":"e1056905"},"PeriodicalIF":0.0,"publicationDate":"2015-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21690707.2015.1056905","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760030","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}