Journal of Proteome Research最新文献_第2页

Large-Scale Quantitative Cross-Linking and Mass Spectrometry Provide New Insight into Protein Conformational Plasticity within Organelles, Cells, and Tissues.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-03-24 DOI: 10.1021/acs.jproteome.4c01030

Andrew Keller, Anna Bakhtina, James E Bruce

{"title":"Large-Scale Quantitative Cross-Linking and Mass Spectrometry Provide New Insight into Protein Conformational Plasticity within Organelles, Cells, and Tissues.","authors":"Andrew Keller, Anna Bakhtina, James E Bruce","doi":"10.1021/acs.jproteome.4c01030","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c01030","url":null,"abstract":"Many proteins can exist in multiple conformational states in vivo to achieve distinct functional roles. These states include alternative conformations, variable post-translational modifications (PTMs), and associations with interacting protein, nucleotide, and ligand partners. Quantitative chemical cross-linking of live cells, organelles, or tissues together with mass spectrometry provides the relative abundance of cross-link levels formed in two or more compared samples, which depends both on the relative levels of existent protein conformational states in the compared samples and on the relative likelihood of the cross-link originating from each. Because cross-link conformational state preferences can vary widely, one expects intraprotein cross-link levels from proteins with high conformational plasticity to display divergent quantitation among samples with differing conformational ensembles. Here we use the large volume of quantitative cross-linking data available on the public XLinkDB database to cluster intraprotein cross-links according to their quantitation in many diverse compared samples to provide the first widescale glimpse of cross-links grouped according to the protein conformational state(s) from which they predominantly originate. We further demonstrate how cluster cross-links can be aligned with any protein structure to assess the likelihood that they were derived from it.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ProSIMSIt: The Best of Both Worlds in Data-Driven Rescoring and Identification Transfer.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-03-22 DOI: 10.1021/acs.jproteome.4c00967

Firas Hamood, Wassim Gabriel, Pia Pfeiffer, Bernhard Kuster, Mathias Wilhelm, Matthew The

引用次数: 0

Sex-Specific Markers of Neuroinflammation and Neurodegeneration in the Spinal Cord Proteome of the SOD1^G93A Mouse Model of Amyotrophic Lateral Sclerosis.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-03-21 DOI: 10.1021/acs.jproteome.4c00990

Liam M Koehn, Joel R Steele, Ralf B Schittenhelm, Joseph A Nicolazzo

{"title":"Sex-Specific Markers of Neuroinflammation and Neurodegeneration in the Spinal Cord Proteome of the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis.","authors":"Liam M Koehn, Joel R Steele, Ralf B Schittenhelm, Joseph A Nicolazzo","doi":"10.1021/acs.jproteome.4c00990","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00990","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that has no cure. The underlying mechanistic details of sex differences in the ALS spinal cord, the site of disease onset, are not understood to an extent that could guide novel drug development. To address this, the spinal cords of 120-day-old wild-type (WT) and SOD1G93A (familial mouse model of ALS with mutant superoxide dismutase 1) mice were subjected to untargeted, quantitative proteomics using tandem mass tag acquisition on high-resolution mass spectrometric instrumentation. Compared to WT, both male and female SOD1G93A spinal cords exhibited an upregulation of neuroinflammatory cascades of both peripheral and central origins, as well as a downregulation of proteins reflective of death and dysfunction of cells within the spinal cord. However, female and male SOD1G93A mouse spinal cords exhibited sex-specific differences in proteins compared to respective WT that related to immune response, as well as cellular structure, function, and homeostasis. The proteomic datasets presented provide entire cohort and sex-specific spinal cord drug targets and disease biomarkers in the SOD1G93A mouse model of ALS that may guide future drug development and sex selection in preclinical study designs utilizing the SOD1G93A model.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Urine Measurements of the Renin-Angiotensin System-Regulated Proteins Predict Death and Graft Loss in Kidney Transplant Recipients Enrolled in a Ramipril versus Placebo Randomized Controlled Trial.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-03-20 DOI: 10.1021/acs.jproteome.4c01100

Sofia Farkona, Max Kotlyar, Kevin Burns, Greg Knoll, Davor Brinc, Igor Jurisica, Ana Konvalinka

{"title":"Urine Measurements of the Renin-Angiotensin System-Regulated Proteins Predict Death and Graft Loss in Kidney Transplant Recipients Enrolled in a Ramipril versus Placebo Randomized Controlled Trial.","authors":"Sofia Farkona, Max Kotlyar, Kevin Burns, Greg Knoll, Davor Brinc, Igor Jurisica, Ana Konvalinka","doi":"10.1021/acs.jproteome.4c01100","DOIUrl":"10.1021/acs.jproteome.4c01100","url":null,"abstract":"The renin-angiotensin system (RAS) is involved in kidney fibrosis. We previously identified six RAS-regulated proteins (RHOB, BST1, LYPA1, GLNA, TSP1, and LAMB2) that were increased in the urine of patients with kidney allograft fibrosis, compared to patients without fibrosis. We hypothesized that these urinary RAS-regulated proteins predicted primary outcomes in kidney transplant recipients enrolled in the largest RAS inhibitor randomized controlled trial. Urine excretion of 10 peptides corresponding to the six RAS-regulated proteins was quantified using parallel reaction monitoring mass spectrometry assays (normalized by urine creatinine) in a subset of patients in the trial. Machine learning models predicting outcomes based on urine peptide excretion rates were developed and evaluated. Urine samples (n = 111) from 56 patients were collected at 0, 6, 12, and 24 months. Twenty-four primary outcomes (doubling of serum creatinine, graft loss, or death) occurred in 17 patients. Logistic regression utilizing eight peptides of TSP1, BST1, LAMB2, LYPA1, and RHOB, from the last urine sample prior to outcomes, predicted a graft loss with an AUC of 0.78 (p = 0.00001). A random forest classifier utilizing BST1 and LYPA1 peptides predicted death with an AUC of 0.80 (p = 0.0016). Urine measurements of RAS-regulated proteins may predict outcomes in kidney transplant recipients, although further prospective studies are required.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quetzal: Comprehensive Peptide Fragmentation Annotation and Visualization.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-03-20 DOI: 10.1021/acs.jproteome.5c00092

Eric W Deutsch, Luis Mendoza, Robert L Moritz

{"title":"Quetzal: Comprehensive Peptide Fragmentation Annotation and Visualization.","authors":"Eric W Deutsch, Luis Mendoza, Robert L Moritz","doi":"10.1021/acs.jproteome.5c00092","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00092","url":null,"abstract":"Proteomics data-dependent acquisition data sets collected with high-resolution mass-spectrometry (MS) can achieve very high-quality results, but nearly every analysis yields results that are thresholded at some accepted false discovery rate, meaning that a substantial number of results are incorrect. For study conclusions that rely on a small number of peptide-spectrum matches being correct, it is thus important to examine at least some crucial spectra to ensure that they are not one of the incorrect identifications. We present Quetzal, a peptide fragment ion spectrum annotation tool to assist researchers in annotating and examining such spectra to ensure that they correctly support study conclusions. We describe how Quetzal annotates spectra using the new Human Proteome Organization (HUPO) Proteomics Standards Initiative (PSI) mzPAF standard for fragment ion peak annotation, including the Python-based code, a web-service end point that provides annotation services, and a web-based application for annotating spectra and producing publication-quality figures. We illustrate its functionality with several annotated spectra of varying complexity. Quetzal provides easily accessible functionality that can assist in the effort to ensure and demonstrate that crucial spectra support study conclusions. Quetzal is publicly available at https://proteomecentral.proteomexchange.org/quetzal/.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Global Profiling of Lactylation Proteomics and Specific Lactylated Site Validation in Rheumatoid Arthritis Patients. 类风湿性关节炎患者乳化蛋白质组学的全局分析和特定乳化位点验证

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-03-20 DOI: 10.1021/acs.jproteome.4c00680

Jiaqi Hu, Zhengyi Jin, Ying Gao, Qilong Liu, Yiyi Yu, Ruina Kong, Dongbao Zhao, Jie Gao

{"title":"Global Profiling of Lactylation Proteomics and Specific Lactylated Site Validation in Rheumatoid Arthritis Patients.","authors":"Jiaqi Hu, Zhengyi Jin, Ying Gao, Qilong Liu, Yiyi Yu, Ruina Kong, Dongbao Zhao, Jie Gao","doi":"10.1021/acs.jproteome.4c00680","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00680","url":null,"abstract":"Protein lactylation is a novel post-translational modification that has rarely been investigated in rheumatoid arthritis (RA). This study aimed to explore lactylation proteomics in RA patients and validate sorted candidate lactylation sites. Synovial tissues from ten RA and six osteoarthritis (OA) patients were subjected to lactylation proteomics via affinity enrichment and LC-MS/MS. Four candidate lactylated modification sites were validated by immunoprecipitation. Totally, 566 sites and 250 proteins with lactylated modifications in RA patients and 548 sites and 220 proteins with lactylated modifications in OA patients were identified. By comparison, 24 upregulated but 2 downregulated lactylated modification sites and 18 upregulated but 1 downregulated lactylated modification protein were discovered in RA patients versus OA patients. The dysregulated lactylated proteins were mainly enriched in biological processes such as positive regulation of plasma membrane repair by GO analysis; pathways such as neutrophil extracellular trap formation by KEGG analysis; and two metabolism-related items by COG/KOG analysis. Immunoprecipitation confirmed that FTH1-K69la (P = 0007) and PKM2-K166la (P = 0.003), but not ANXA2-K115la (P = 0.127) or ANXA5-K76la (P = 0.361), were more abundant in RA patients versus OA patients. Moreover, FTH1-K69la was positively correlated with erythrocyte sedimentation rate (ESR) in RA patients (P = 0.037). Conclusively, this study describes a general landscape of lactylation proteomics in the RA.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HRaDeX: R Package and Web Server for Computing High-Resolution Deuterium Uptake Rates for HDX-MS Data.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-03-19 DOI: 10.1021/acs.jproteome.4c00700

Weronika Puchała, Michał Kistowski, Liliya Zhukova, Michał Burdukiewicz, Michał Dadlez

引用次数: 0

Metabolomics- and Proteomics-Based Disease Diagnostic Classifier Model for the Prediction and Diagnosis of Colorectal Carcinoma.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-03-19 DOI: 10.1021/acs.jproteome.5c00010

Zhaorui Wang, Tianyuan Li, Mengyao Sun, Na Liu, Haozhe Zhang, Zhikun Feng, Ningjing Lei

{"title":"Metabolomics- and Proteomics-Based Disease Diagnostic Classifier Model for the Prediction and Diagnosis of Colorectal Carcinoma.","authors":"Zhaorui Wang, Tianyuan Li, Mengyao Sun, Na Liu, Haozhe Zhang, Zhikun Feng, Ningjing Lei","doi":"10.1021/acs.jproteome.5c00010","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00010","url":null,"abstract":"Background: Colorectal carcinoma (CRC) is a leading cause of cancer-related deaths globally. Diagnostic biomarkers are essential for risk stratification and early detection, potentially enhancing patient survival. Our study aimed to explore the potential biomarkers of CRC at the protein and metabolic levels.Methods: Blood serum from CRC patients and healthy controls was analyzed using metabolomic and proteomic techniques. A conjoint analysis was conducted, and samples were split into training and validation sets (7:3 ratio) to develop and evaluate a disease diagnosis classifier model. Immunohistochemistry (IHC) analyses were conducted to validate the results.Results: We identified 631 differential metabolites and 61 differentially expressed proteins (DEPs) in CRC, involved in pathways such as arginine and proline metabolism, central carbon metabolism in cancer, and signaling pathways including TGF-β, mTOR, PI3K-Akt, and others. Key proteins (CILP2, SLC3A2, EXTL2, hydroxypyruvate isomerase (HYI), ENPEP, LRG1, CTSS, thyrotropin-releasing hormone-degrading ectoenzyme (TRHDE), SELE, and HSPA1A) showed significant expression differences between CRC patients and controls. IHC results showed that compared with the paracancerous tissues, the expression of CILP2, EXTL2, and HYI was significantly downregulated in the CRC tissues (P < 0.05). The classifier model, comprising l-arginine, Harden-Young ester, l-aspartic acid, oxoglutaric acid, l-proline, octopine, l-valine, and progesterone, achieved AUC values of 0.998 and 0.914 in training and validation data sets, respectively.Conclusions: The identified metabolites and DEPs are promising CRC biomarkers. The developed classifier model based on eight metabolites demonstrates high accuracy for CRC assessment and diagnosis.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improved Method to Determine Protein Turnover Rates with Heavy Water Labeling by Mass Isotopomer Ratio Selection.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-03-18 DOI: 10.1021/acs.jproteome.4c01012

Jordan Currie, Dominic C M Ng, Boomathi Pandi, Alexander Black, Vyshnavi Manda, Cheyanne Durham, Jay Pavelka, Maggie P Y Lam, Edward Lau

{"title":"Improved Method to Determine Protein Turnover Rates with Heavy Water Labeling by Mass Isotopomer Ratio Selection.","authors":"Jordan Currie, Dominic C M Ng, Boomathi Pandi, Alexander Black, Vyshnavi Manda, Cheyanne Durham, Jay Pavelka, Maggie P Y Lam, Edward Lau","doi":"10.1021/acs.jproteome.4c01012","DOIUrl":"10.1021/acs.jproteome.4c01012","url":null,"abstract":"The synthesis and degradation rates of proteins form an essential component of gene expression control. Heavy water labeling has been used in conjunction with mass spectrometry to measure protein turnover rates, but the optimal analytical approaches to derive turnover rates from the mass isotopomer patterns of deuterium-labeled peptides continue to be a subject of research. Here, we describe a method that comprises (1) a nearest lookup of numerically approximated peptide isotope envelopes, coupled to (2) the selection of optimal mass isotopomer pairs based on peptide sequence rules, to calculate the molar fraction of new peptide synthesis in heavy water labeling mass spectrometry experiments. We validated our approach using an experimental calibration standard comprising mixtures of fully unlabeled and fully labeled proteomes. We then reanalyzed 17 proteome-wide turnover experiments from four mouse organs across multiple data sets and showed that the combined nearest-lookup and rule-based mass isotopomer ratio selection method increases the coverage of well-fitted peptides in protein turnover experiments by up to 58 ± 13%. The workflow is implemented in the Riana software tool for protein turnover analysis and may avail ongoing efforts to study the synthesis and degradation kinetics of proteins in animals on a proteome-wide scale.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

3-Hydroxybutyrate Promotes Myoblast Proliferation and Differentiation through Energy Metabolism and GPR109a-Mediated Ca²⁺-NFAT Signaling Pathways.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-03-18 DOI: 10.1021/acs.jproteome.4c01150

Xu Qiu, Wenfang Wu, Shuya Zhang, Caihua Huang, Donghai Lin

{"title":"3-Hydroxybutyrate Promotes Myoblast Proliferation and Differentiation through Energy Metabolism and GPR109a-Mediated Ca2+-NFAT Signaling Pathways.","authors":"Xu Qiu, Wenfang Wu, Shuya Zhang, Caihua Huang, Donghai Lin","doi":"10.1021/acs.jproteome.4c01150","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c01150","url":null,"abstract":"Skeletal muscle wasting is a critical clinical problem associated with several diseases that significantly impair patient outcomes due to the progressive loss of muscle mass and function. This study explores the potential of 3-hydroxybutyrate (3-HB) as a therapeutic agent to counteract muscle atrophy by promoting the proliferation and differentiation of C2C12 myoblasts. Using nuclear magnetic resonance (NMR)-based metabolomics analysis, we uncover the underlying mechanisms by which 3-HB exerts its effects. Our findings demonstrate that 3-HB exerts its effects through two distinct mechanisms: as a metabolic substrate and as a signaling molecule. As a metabolic substrate, 3-HB enhances myoblast energy efficiency by stimulating the expression of G protein-coupled receptor 109a (GPR109a), which subsequently upregulates the 3-HB transporters MCT1 and CD147, the utilization enzyme OXCT1, and phosphorylated AMPK, thereby increasing ATP production. As a signaling molecule, 3-HB activates GPR109a, promoting calcium influx, improving calcium homeostasis, and increasing the expression of Ca2+-related proteins such as CAMKK2. This signaling cascade activates calcineurin (CaN), facilitating NFAT translocation to the nucleus and gene expression that drives myoblast proliferation and differentiation. By elucidating the dual regulatory roles of 3-HB in energy metabolism and cellular signaling, this study not only advances our understanding of muscle physiology but also highlights the potential of 3-HB as a novel therapeutic approach for the prevention or treatment of skeletal muscle atrophy.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0