Journal of proteins and proteomics最新文献

{"title":"The effects of retinal disease on intrinsic protein disorder and liquid-liquid‑phase separation.","authors":"Nedym Hadzijahic, Colin K Kim, Mak B Djulbegovic, Michael Antonietti, David J Taylor Gonzalez, Vladimir N Uversky, Jose S Pulido, Carol L Karp","doi":"10.1007/s42485-025-00188-6","DOIUrl":"10.1007/s42485-025-00188-6","url":null,"abstract":"<p><strong>Background: </strong>The human retina is integral to vision, converting light into neural signals through a complex interplay of specialized neuronal cell types. Recent proteomic studies have revealed significant insights into retinal function, yet much of the retina's proteome remains unexplored. Our research focuses on quantifying and characterizing intrinsically disordered proteins (IDPs) and regions (IDRs) within the retina and other ocular structures. These proteins are critical for cellular processes due to their flexible, structure-less nature, allowing for versatile interactions in signaling and regulatory networks. Furthermore, we investigate the phenomenon of liquid-liquid-phase separation (LLPS), a process vital for cellular organization and implicated in various diseases, within the retina proteome.</p><p><strong>Methods: </strong>In this study, we employed a suite of bioinformatics and deep learning tools to analyze protein intrinsic disorder and the propensity for LLPS in proteomes from both healthy and diseased retinas. We utilized the Human Protein Atlas (HPA) as a baseline control, comparing it against the RetNet protein set and samples afflicted by age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) with and without gliosis. Protein sequences were sourced from the universal protein resource (UniProt) and analyzed for intrinsic disorder using the rapid intrinsic disorder analysis online (RIDAO) platform. Disorder levels and phase separation tendencies were further examined through statistical analyses, including ANOVA and chi-squared tests, to evaluate differences across proteomes. In addition, we assessed the likelihood of proteins to undergo LLPS using predictive tools, such as PSPredictor and ParSe V2, integrating these findings with intrinsic disorder data to draw comprehensive conclusions about the structural dynamics within these proteomes.</p><p><strong>Results: </strong>The HPA control proteome displayed the highest levels of intrinsic disorder, significantly greater than those observed in disease-specific proteomes, including those affected by AMD, glaucoma, and diabetic retinopathy with and without gliosis. CH-CDF plot analysis revealed distinct structural profiles, with a higher proportion of structured proteins in the HPA and molten globular states prevalent in disease states. Our findings highlight a marked disparity in LLPS propensity, with the HPA proteome and the RetNet Protein Set demonstrating the greatest potential, suggesting a disease-specific alteration in protein interaction dynamics and structural organization.</p><p><strong>Discussion: </strong>This study revealed significant variations in protein intrinsic disorder and liquid-LLPS across healthy and diseased retinal proteomes. The highest levels of disorder in the HPA proteome suggest a proteomic flexibility that is critical for normal retinal function. In contrast, the AMD and glaucoma proteomes, with their lower d","PeriodicalId":73910,"journal":{"name":"Journal of proteins and proteomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839264","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 CYP1B1 and its implications in primary congenital glaucoma pathogenesis.","authors":"Meghan Sharma, David Taylor Gonzalez, Michael Antonietti, Vladimir Uversky, Mak Djulbegovic","doi":"10.1007/s42485-025-00186-8","DOIUrl":"10.1007/s42485-025-00186-8","url":null,"abstract":"<p><p>Cytochrome P450 1B1 (CYP1B1) plays a critical role in the pathogenesis of primary congenital glaucoma (PCG), a severe eye disorder that can lead to pediatric blindness if untreated. Increasing evidence suggests that intrinsically disordered proteins and regions (IDPs/IDPRs), which lack a stable three-dimensional structure, are significant in disease pathology due to their flexible nature, impacting protein interactions and function. This study explores the intrinsic disorder within CYP1B1 and its implications in the molecular mechanisms underlying PCG. We employed a comprehensive bioinformatics approach to assess the structural and functional properties of CYP1B1 using tools such as AlphaMissense, a tool crafted to evaluate the functional impact of missense mutations in proteins. Our structural analysis qualitatively demonstrated that CYP1B1 contains intrinsically disordered protein regions (i.e., spaghetti-like entities) that are structureless and flexible. Correlation analysis showed that disorder decreases exponentially relative to AlphaMissense predicted pathogenicity, with an exponential decay fit (<i>R</i> ² = 0.62), suggesting that highly disordered regions tend to harbor benign mutations. This study identifies critical intrinsically disordered regions within CYP1B1 and elucidates its complex interaction network, highlighting the potential role of these regions in PCG pathogenesis. The observed correlation between intrinsic disorder and reduced pathogenicity of mutations suggests that IDPRs may buffer against deleterious effects, providing a possible explanation for the variability in clinical outcomes associated with CYP1B1 mutations. These insights enhance our understanding of the molecular basis of PCG and offer potential targets for novel therapeutic interventions to combat this blinding childhood disorder.</p>","PeriodicalId":73910,"journal":{"name":"Journal of proteins and proteomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877160","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":"Progress in mass spectrometry approaches to profiling protein-protein interactions in the studies of the innate immune system.","authors":"Doeun Kim, Aleksandra Nita-Lazar","doi":"10.1007/s42485-024-00156-6","DOIUrl":"10.1007/s42485-024-00156-6","url":null,"abstract":"<p><p>Understanding protein-protein interactions (PPIs) is pivotal for deciphering the intricacies of biological processes. Dysregulation of PPIs underlies a spectrum of diseases, including cancer, neurodegenerative disorders, and autoimmune conditions, highlighting the imperative of investigating these interactions for therapeutic advancements. This review delves into the realm of mass spectrometry-based techniques for elucidating PPIs and their profound implications in biological research. Mass spectrometry in the PPI research field not only facilitates the evaluation of protein-protein interaction modulators but also discovers unclear molecular mechanisms and sheds light on both on- and off-target effects, thus aiding in drug development. Our discussion navigates through six pivotal techniques: affinity purification mass spectrometry (AP-MS), proximity labeling mass spectrometry (PL-MS), cross-linking mass spectrometry (XL-MS), size exclusion chromatography coupled with mass spectrometry (SEC-MS), limited proteolysis-coupled mass spectrometry (LiP-MS), and thermal proteome profiling (TPP).</p>","PeriodicalId":73910,"journal":{"name":"Journal of proteins and proteomics","volume":"15 3","pages":"545-559"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395753","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":"Investigating the ATP-binding pocket of CX3CL1-binding protein 2 using in silico approach","authors":"Rimjhim Kumari, Satinder Kaur, Rachna Hora, P. Mishra","doi":"10.1007/s42485-024-00133-z","DOIUrl":"https://doi.org/10.1007/s42485-024-00133-z","url":null,"abstract":"","PeriodicalId":73910,"journal":{"name":"Journal of proteins and proteomics","volume":"108 45","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140380405","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":"Prediction of B cell epitopes in envelope protein of dengue virus using immunoinformatics approach","authors":"Ajay Kumar, Siddharth Gupta, Hari Sharan, Fariya Khan","doi":"10.1007/s42485-024-00134-y","DOIUrl":"https://doi.org/10.1007/s42485-024-00134-y","url":null,"abstract":"","PeriodicalId":73910,"journal":{"name":"Journal of proteins and proteomics","volume":" 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140381861","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":"Identification of potential inhibitors of shikimate kinase from Mycobacterium tuberculosis using in silico approach","authors":"M. A. Isa, Mohammed Mustapha Mohammed, Muhammad Musa Ibrahim, F. Gubio, Fatimah Buba, Somia Shehzadi","doi":"10.1007/s42485-024-00132-0","DOIUrl":"https://doi.org/10.1007/s42485-024-00132-0","url":null,"abstract":"","PeriodicalId":73910,"journal":{"name":"Journal of proteins and proteomics","volume":" 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140221909","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":"Tree based models for classification of membrane and secreted proteins in heart","authors":"Sona Charles, A. Subeesh, Jeyakumar Natarajan","doi":"10.1007/s42485-024-00131-1","DOIUrl":"https://doi.org/10.1007/s42485-024-00131-1","url":null,"abstract":"","PeriodicalId":73910,"journal":{"name":"Journal of proteins and proteomics","volume":" 49","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140221227","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":"Histone protein profiling in rice reveals a correlation between canonical and noncanonical function and evolution","authors":"Atreyee Sengupta, Kanika Narula, Archana Sharma, N. Chakraborty, S. Chakraborty","doi":"10.1007/s42485-024-00129-9","DOIUrl":"https://doi.org/10.1007/s42485-024-00129-9","url":null,"abstract":"","PeriodicalId":73910,"journal":{"name":"Journal of proteins and proteomics","volume":"34 8","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140084567","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":"An immunoinformatics study to explore HTL epitopes for fungal pathogen Aspergillus lentulus","authors":"Shreesh Kumar Dubey, Manoj Kumar Mishra, Fariya Khan, N. Akhtar, Ajay Kumar","doi":"10.1007/s42485-023-00125-5","DOIUrl":"https://doi.org/10.1007/s42485-023-00125-5","url":null,"abstract":"","PeriodicalId":73910,"journal":{"name":"Journal of proteins and proteomics","volume":"43 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139603532","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":"Interrogating data-independent acquisition LC-MS/MS for affinity proteomics.","authors":"David L Tabb, Mohammed Hanzala Kaniyar, Omar G Rosas Bringas, Heaji Shin, Luciano Di Stefano, Martin S Taylor, Shaoshuai Xie, Omer H Yilmaz, John LaCava","doi":"10.1007/s42485-024-00166-4","DOIUrl":"10.1007/s42485-024-00166-4","url":null,"abstract":"<p><p>Data-Independent Acquisition (DIA) LC-MS/MS is an attractive partner for co-immunoprecipitation (co-IP) and affinity proteomics in general. Reducing the variability of quantitation by DIA could increase the statistical contrast for detecting specific interactors versus what has been achieved in Data-Dependent Acquisition (DDA). By interrogating affinity proteomes featuring both DDA and DIA experiments, we sought to evaluate the spectral libraries, the missingness of protein quantity tables, and the CV of protein quantities in six studies representing three different instrument manufacturers. We examined four contemporary bioinformatics workflows for DIA: FragPipe, DIA-NN, Spectronaut, and MaxQuant. We determined that (1) identifying spectral libraries directly from DIA experiments works well enough that separate DDA experiments do not produce larger spectral libraries when given equivalent instrument time; (2) experiments involving mock pull-downs or IgG controls may feature such indistinct signals that contemporary software will struggle to quantify them; (3) measured CV values were well controlled by Spectronaut and DIA-NN (and FragPipe, which implements DIA-NN for the quantitation step); and (4) when FragPipe builds spectral libraries and quantifies proteins from DIA experiments rather than performing both operations in DDA experiments, the DIA route results in a larger number of proteins quantified without missing values as well as lower CV for measured protein quantities.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s42485-024-00166-4.</p>","PeriodicalId":73910,"journal":{"name":"Journal of proteins and proteomics","volume":"15 3","pages":"281-298"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382674","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}