Journal of Proteome Research最新文献_第9页

H-NOX Influences Biofilm Formation, Central Metabolism, and Quorum Sensing in Paracoccus denitrificans H-NOX 影响反硝化副球菌的生物膜形成、中央代谢和法定量感应

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-06 DOI: 10.1021/acs.jproteome.4c0046610.1021/acs.jproteome.4c00466

Md. Shariful Islam, Aishat Alatishe, Cameron C. Lee-Lopez, Fred Serrano and Erik T. Yukl*,

{"title":"H-NOX Influences Biofilm Formation, Central Metabolism, and Quorum Sensing in Paracoccus denitrificans","authors":"Md. Shariful Islam, Aishat Alatishe, Cameron C. Lee-Lopez, Fred Serrano and Erik T. Yukl*, ","doi":"10.1021/acs.jproteome.4c0046610.1021/acs.jproteome.4c00466","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00466https://doi.org/10.1021/acs.jproteome.4c00466","url":null,"abstract":"The transition from planktonic to biofilm growth in bacteria is often accompanied by greater resistance to antibiotics and other stressors, as well as distinct alterations in physical traits, genetic activity, and metabolic restructuring. In many species, the heme nitric oxide/oxygen binding proteins (H-NOX) play an important role in this process, although the signaling mechanisms and pathways in which they participate are quite diverse and largely unknown. In Paracoccus denitrificans, deletion of the hnox gene results in a severe biofilm-deficient phenotype. Quantitative proteomics was used to assemble a comprehensive data set of P. denitrificans proteins showing altered abundance of those involved in several important metabolic pathways. Further, decreased levels of pyruvate and elevated levels of C16 homoserine lactone were detected for the Δhnox strain, associating the biofilm deficiency with altered central carbon metabolism and quorum sensing, respectively. These results expand our knowledge of the important role of H-NOX signaling in biofilm formation.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jproteome.4c00466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leveraging Supervised Machine Learning Algorithms for System Suitability Testing of Mass Spectrometry Imaging Platforms. 利用监督机器学习算法对质谱成像平台进行系统适用性测试。

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-04 Epub Date: 2024-09-03 DOI: 10.1021/acs.jproteome.4c00360

Russell R Kibbe, Alexandria L Sohn, David C Muddiman

{"title":"Leveraging Supervised Machine Learning Algorithms for System Suitability Testing of Mass Spectrometry Imaging Platforms.","authors":"Russell R Kibbe, Alexandria L Sohn, David C Muddiman","doi":"10.1021/acs.jproteome.4c00360","DOIUrl":"10.1021/acs.jproteome.4c00360","url":null,"abstract":"Quality control and system suitability testing are vital protocols implemented to ensure the repeatability and reproducibility of data in mass spectrometry investigations. However, mass spectrometry imaging (MSI) analyses present added complexity since both chemical and spatial information are measured. Herein, we employ various machine learning algorithms and a novel quality control mixture to classify the working conditions of an MSI platform. Each algorithm was evaluated in terms of its performance on unseen data, validated with negative control data sets to rule out confounding variables or chance agreement, and utilized to determine the necessary sample size to achieve a high level of accurate classifications. In this work, a robust machine learning workflow was established where models could accurately classify the instrument condition as clean or compromised based on data metrics extracted from the analyzed quality control sample. This work highlights the power of machine learning to recognize complex patterns in MSI data and use those relationships to perform a system suitability test for MSI platforms.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124142","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

Proteomics Analysis of Renal Cell Line Caki-2 with AFMID Overexpression and Potential Biomarker Discovery in Urine. AFMID过表达的肾细胞系Caki-2的蛋白质组学分析及尿液中潜在生物标记物的发现

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-04 Epub Date: 2024-08-30 DOI: 10.1021/acs.jproteome.4c00431

Jiameng Sun, Jinchun Chang, Zhengguang Guo, Haidan Sun, Jiyu Xu, Xiaoyan Liu, Wei Sun

{"title":"Proteomics Analysis of Renal Cell Line Caki-2 with AFMID Overexpression and Potential Biomarker Discovery in Urine.","authors":"Jiameng Sun, Jinchun Chang, Zhengguang Guo, Haidan Sun, Jiyu Xu, Xiaoyan Liu, Wei Sun","doi":"10.1021/acs.jproteome.4c00431","DOIUrl":"10.1021/acs.jproteome.4c00431","url":null,"abstract":"Aromatic caninurine formamase (AFMID) is an enzyme involved in the tryptophan pathway, metabolizing N-formylkynurenine to kynurenine. AFMID had been found significantly downregulated in clear cell renal cell carcinoma (ccRCC) in both tissue and urine samples. Although ccRCC is characterized by a typical Warburg-like phenotype, mitochondrial dysfunction, and elevated fat deposition, it is unknown whether AFMID plays a role in tumorigenesis and the development of ccRCC. In the present study, AFMID overexpression had inhibitory effects for ccRCC cells, decreasing the rate of cell proliferation. Quantitative proteomics showed that AFMID overexpression altered cellular signaling pathways involved in cell growth and cellular metabolism pathways, including lipid metabolism and inositol phosphate metabolism. Further urine proteomic analysis indicated that cellular function dysfunction with AFMID overexpression could be reflected in the urine. The activity of predicted upregulators DDX58, TREX1, TGFB1, SMARCA4, and TNF in ccRCC cells and urine showed opposing change trends. Potential urinary biomarkers were tentatively discovered and further validated using an independent cohort. The protein panel of APOC3, UMOD, and CILP achieved an AUC value of 0.862 for the training cohort and 0.883 for the validation cohort. The present study is of significance in terms of highlighting various aspects of pathway changes associated with AFMID enzymes, discovering potential specific biomarkers for potential patient diagnosis, and therapeutic targeting.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102195","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

AnnoDUF: A Web-Based Tool for Annotating Functions of Proteins Having Domains of Unknown Function. AnnoDUF：一种基于网络的工具，用于标注具有未知功能域的蛋白质的功能。

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-04 Epub Date: 2024-08-31 DOI: 10.1021/acs.jproteome.4c00251

Aman Vishwakarma, Namrata Padmashali, Saravanamuthu Thiyagarajan

{"title":"AnnoDUF: A Web-Based Tool for Annotating Functions of Proteins Having Domains of Unknown Function.","authors":"Aman Vishwakarma, Namrata Padmashali, Saravanamuthu Thiyagarajan","doi":"10.1021/acs.jproteome.4c00251","DOIUrl":"10.1021/acs.jproteome.4c00251","url":null,"abstract":"The rapid expansion of biological sequence databases due to high-throughput genomic and proteomic sequencing methods has left a considerable number of identified protein sequences with unclear or incomplete functional annotations. Domains of unknown function (DUFs) are protein domains that lack functional annotations but are present in numerous proteins. To address the challenge of finding functional annotations for DUFs, we have developed a computational method that efficiently identifies and annotates these enigmatic protein domains by utilizing the position-specific iterative basic local alignment search tool (PSI-BLAST) and data mining techniques. Our pipeline identifies putative potential functionalities of DUFs, thereby decreasing the gap between known sequences and functions. The tool can also take user input sequences to annotate. We executed our pipeline on 5111 unique DUF sequences obtained from Pfam, resulting in putative annotations for 2007 of these. These annotations were subsequently incorporated into a comprehensive database and interfaced with a web-based server named \"AnnoDUF\". AnnoDUF is freely accessible to both academic and industrial users, via the World Wide Web at the link http://bts.ibab.ac.in/annoduf.php. All scripts used in this study are uploaded to the GitHub repository, and these can be accessed from https://github.com/BioToolSuite/AnnoDUF.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102190","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

Plasma Inflammation Markers Linked to Complications and Outcomes after Spontaneous Intracerebral Hemorrhage. 血浆炎症标记物与自发性脑内出血后的并发症和预后有关

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-04 Epub Date: 2024-09-03 DOI: 10.1021/acs.jproteome.4c00311

Xiao Cheng, Dafeng Hu, Chengyi Wang, Ting Lu, Zhenqiu Ning, Kunhong Li, Zhixuan Ren, Yan Huang, Lihua Zhou, Sookja Kim Chung, Zhenchuan Liu, Zhangyong Xia, Wei Meng, Guanghai Tang, Jingbo Sun, Jianwen Guo

{"title":"Plasma Inflammation Markers Linked to Complications and Outcomes after Spontaneous Intracerebral Hemorrhage.","authors":"Xiao Cheng, Dafeng Hu, Chengyi Wang, Ting Lu, Zhenqiu Ning, Kunhong Li, Zhixuan Ren, Yan Huang, Lihua Zhou, Sookja Kim Chung, Zhenchuan Liu, Zhangyong Xia, Wei Meng, Guanghai Tang, Jingbo Sun, Jianwen Guo","doi":"10.1021/acs.jproteome.4c00311","DOIUrl":"10.1021/acs.jproteome.4c00311","url":null,"abstract":"Intracerebral hemorrhage (ICH) could trigger inflammatory responses. However, the specific role of inflammatory proteins in the pathological mechanism, complications, and prognosis of ICH remains unclear. In this study, we investigated the expression of 92 plasma inflammation-related proteins in patients with ICH (n = 55) and healthy controls (n = 20) using an Olink inflammation panel and discussed the relation to the severity of stroke, clinical complications, 30-day mortality, and 90-day outcomes. Our result showed that six proteins were upregulated in ICH patients compared with healthy controls, while seventy-four proteins were downregulated. In patients with ICH, seven proteins were increased in the severe stroke group compared with the moderate stroke group. In terms of complications, two proteins were downregulated in patients with pneumonia, while nine proteins were upregulated in patients with sepsis. Compared with the survival group, three proteins were upregulated, and one protein was downregulated in the death group. Compared with the good outcome group, eight proteins were upregulated, and four proteins were downregulated in the poor outcome group. In summary, an in-depth exploration of the differential inflammatory factors in the early stages of ICH could deepen our understanding of the pathogenesis of ICH, predict patient prognosis, and explore new treatment strategies.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118331","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

Olink Proteomics for the Identification of Biomarkers for Early Diagnosis of Postmenopausal Osteoporosis. Olink 蛋白质组学用于绝经后骨质疏松症早期诊断生物标志物的鉴定。

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-04 Epub Date: 2024-09-03 DOI: 10.1021/acs.jproteome.4c00470

Chunyan Li, Xinwei Zang, Heng Liu, Shangqi Yin, Xiang Cheng, Wei Zhang, Xiangyu Meng, Liyuan Chen, Shuai Lu, Jun Wu

{"title":"Olink Proteomics for the Identification of Biomarkers for Early Diagnosis of Postmenopausal Osteoporosis.","authors":"Chunyan Li, Xinwei Zang, Heng Liu, Shangqi Yin, Xiang Cheng, Wei Zhang, Xiangyu Meng, Liyuan Chen, Shuai Lu, Jun Wu","doi":"10.1021/acs.jproteome.4c00470","DOIUrl":"10.1021/acs.jproteome.4c00470","url":null,"abstract":"This investigation aims to employ Olink proteomics in analyzing the distinct serum proteins associated with postmenopausal osteoporosis (PMOP) and identifying prognostic markers for early detection of PMOP via molecular mechanism research on postmenopausal osteoporosis. Postmenopausal women admitted to Beijing Jishuitan Hospital were randomly selected and categorized into three groups based on their dual-energy X-ray absorptiometry (DXA) T-scores: osteoporosis group (n = 24), osteopenia group (n = 20), and normal bone mass group (n = 16). Serum samples from all participants were collected for clinical and bone metabolism marker measurements. Olink proteomics was utilized to identify differentially expressed proteins (DEPs) that are highly associated with postmenopausal osteoporosis. The functional analysis of DEPs was performed using Gene Ontology and Kyto Encyclopedia Genes and Genomes (KEGG). The biological characteristics of these proteins and their correlation with PMOP were subsequently analyzed. ROC curve analysis was performed to identify potential biomarkers with the highest diagnostic accuracy for early stage PMOP. Through Olink proteomics, we identified five DEPs highly associated with PMOP, including two upregulated and three downregulated proteins. TWEAK and CDCP1 markers exhibited the highest area under the curve (0.8188 and 0.8031, respectively). TWEAK and CDCP1 have the potential to serve as biomarkers for early prediction of postmenopausal osteoporosis.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteome and Glycoproteome Analyses Reveal Regulation of Protein Glycosylation Site-Specific Occupancy and Lysosomal Hydrolase Maturation by N-Glycan-Dependent ER-Quality Control. 蛋白质组和糖蛋白组分析揭示了 N-糖依赖性 ER 质量控制对蛋白质糖基化位点特异性占据和溶酶体水解酶成熟的调控。

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-04 Epub Date: 2024-09-05 DOI: 10.1021/acs.jproteome.4c00378

Jingru Chen, Piaopiao Wen, Yu-He Tang, Hanjie Li, Zibo Wang, Xiuyuan Wang, Xiaoman Zhou, Xiao-Dong Gao, Morihisa Fujita, Ganglong Yang

{"title":"Proteome and Glycoproteome Analyses Reveal Regulation of Protein Glycosylation Site-Specific Occupancy and Lysosomal Hydrolase Maturation by N-Glycan-Dependent ER-Quality Control.","authors":"Jingru Chen, Piaopiao Wen, Yu-He Tang, Hanjie Li, Zibo Wang, Xiuyuan Wang, Xiaoman Zhou, Xiao-Dong Gao, Morihisa Fujita, Ganglong Yang","doi":"10.1021/acs.jproteome.4c00378","DOIUrl":"10.1021/acs.jproteome.4c00378","url":null,"abstract":"N-Glycan-dependent endoplasmic reticulum quality control (ERQC) primarily mediates protein folding, which determines the fate of the polypeptide. Monoglucose residues on N-glycans determine whether the nascent N-glycosylated proteins enter into and escape from the calnexin (CANX)/calreticulin (CALR) cycle, which is a central system of the ERQC. To reveal the impact of ERQC on glycosylation and protein fate, we performed comprehensive quantitative proteomic and glycoproteomic analyses using cells defective in N-glycan-dependent ERQC. Deficiency of MOGS encoding the ER α-glucosidase I, CANX, or/and CALR broadly affected protein expression and glycosylation. Among the altered glycoproteins, the occupancy of oligomannosidic N-glycans was significantly affected. Besides the expected ER stress, proteins and glycoproteins involved in pathways for lysosome and viral infection are differentially changed in those deficient cells. We demonstrated that lysosomal hydrolases were not correctly modified with mannose-6-phosphates on the N-glycans and were directly secreted to the culture medium in N-glycan-dependent ERQC mutant cells. Overall, the CANX/CALR cycle promotes the correct folding of glycosylated peptides and influences the transport of lysosomal hydrolases.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131086","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

Characteristics of Myocardial Structure and Central Carbon Metabolism during the Early and Compensatory Stages of Cardiac Hypertrophy. 心肌肥大早期和代偿期的心肌结构和中枢碳代谢特征

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-04 Epub Date: 2024-08-23 DOI: 10.1021/acs.jproteome.4c00142

Yuan Chen, Yu-Mei Luo, Dong Li, Haiqiong Liu, Xiaoqin Luo, Xinlei Zhang, Yuanna Ling, Wei Ouyang

{"title":"Characteristics of Myocardial Structure and Central Carbon Metabolism during the Early and Compensatory Stages of Cardiac Hypertrophy.","authors":"Yuan Chen, Yu-Mei Luo, Dong Li, Haiqiong Liu, Xiaoqin Luo, Xinlei Zhang, Yuanna Ling, Wei Ouyang","doi":"10.1021/acs.jproteome.4c00142","DOIUrl":"10.1021/acs.jproteome.4c00142","url":null,"abstract":"Cardiac hypertrophy is a classical forerunner of heart failure and myocardial structural and metabolic remodeling are closely associated with cardiac hypertrophy. We aim to investigate the characteristics of myocardial structure and central carbon metabolism of cardiac hypertrophy at different stages. Using echocardiography and pathological staining, early and compensatory cardiac hypertrophy were respectively defined as within 7 days and from 7 to 14 days after transverse aortic constriction (TAC) in mice. Among mass-spectrometry-based metabolomics, we identified 45 central carbon metabolites. Differential metabolite analysis showed that six metabolites, including citrate, cis-aconitate and so on, decreased significantly on day 1 after TAC. Ten metabolites, including l-lactate, (S)-2-hydroxyglutarate and so on, were obviously changed on days 10 and 14. Pathway analysis showed that these metabolites were involved in seven metabolic pathways, including carbohydrates, amino acids and so on. Western blot showed the expression of ATP-citrate lyase, malate dehydrogenase 1 and lactate dehydrogenase A in myocardium changed markedly on day 3, while the phosphorylation level of AMP-activated protein kinase did not show significantly difference. We hope our research will promote deeper understanding and early diagnosis of cardiac hypertrophy in clinical practice. All raw data were deposited in MetaboLights (MTBLS10555).","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142043787","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

Mapping Extracellular Protein-Protein Interactions Using Extracellular Proximity Labeling (ePL). 利用细胞外接近标记（ePL）绘制细胞外蛋白质-蛋白质相互作用图。

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-04 Epub Date: 2024-09-05 DOI: 10.1021/acs.jproteome.4c00606

David Peeney, Sadeechya Gurung, Joshua A Rich, Sasha Coates-Park, Yueqin Liu, Jack Toor, Jane Jones, Christopher T Richie, Lisa M Jenkins, William G Stetler-Stevenson

{"title":"Mapping Extracellular Protein-Protein Interactions Using Extracellular Proximity Labeling (ePL).","authors":"David Peeney, Sadeechya Gurung, Joshua A Rich, Sasha Coates-Park, Yueqin Liu, Jack Toor, Jane Jones, Christopher T Richie, Lisa M Jenkins, William G Stetler-Stevenson","doi":"10.1021/acs.jproteome.4c00606","DOIUrl":"10.1021/acs.jproteome.4c00606","url":null,"abstract":"Proximity labeling (PL) has given researchers the tools to explore protein-protein interactions (PPIs) in living systems; however, most PL studies are performed on intracellular targets. We have adapted the original PL method to investigate PPIs within the extracellular compartment, which we term extracellular PL (ePL). To demonstrate the utility of this modified technique, we investigated the interactome of the matrisome protein TIMP2. TIMPs are a family of multifunctional proteins that were initially defined by their ability to inhibit metalloproteinases, the major mediators of extracellular matrix (ECM) turnover. TIMP2 exhibits broad expression and is often abundant in both normal and diseased tissues. Understanding the functional transformation of matrisome regulators, such as TIMP2, during disease progression is essential for the development of ECM-targeted therapeutics. Using dual orientation fusion proteins of TIMP2 with BioID2/TurboID, we describe the TIMP2 proximal interactome (MassIVE MSV000095637). We also illustrate how the TIMP2 interactome changes in the presence of different stimuli, in different cell types, in unique culture conditions (2D vs 3D), and with different reaction kinetics, demonstrating the power of this technique versus classical PPI methods. We propose that screening of matrisome targets in disease models using ePL will reveal new therapeutic targets for further comprehensive studies.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional and Proteomic Dissection of the Contributions of CodY, SigB and the Hibernation Promoting Factor HPF to Interactions of Staphylococcus aureus USA300 with Human Lung Epithelial Cells. 从功能和蛋白质组学角度剖析 CodY、SigB 和冬眠促进因子 HPF 对金黄色葡萄球菌 USA300 与人类肺上皮细胞相互作用的贡献。

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-04 Epub Date: 2024-09-20 DOI: 10.1021/acs.jproteome.4c00724

Xiaofang Li, Larissa M Busch, Sjouke Piersma, Min Wang, Lei Liu, Manuela Gesell Salazar, Kristin Surmann, Ulrike Mäder, Uwe Völker, Girbe Buist, Jan Maarten van Dijl

{"title":"Functional and Proteomic Dissection of the Contributions of CodY, SigB and the Hibernation Promoting Factor HPF to Interactions of Staphylococcus aureus USA300 with Human Lung Epithelial Cells.","authors":"Xiaofang Li, Larissa M Busch, Sjouke Piersma, Min Wang, Lei Liu, Manuela Gesell Salazar, Kristin Surmann, Ulrike Mäder, Uwe Völker, Girbe Buist, Jan Maarten van Dijl","doi":"10.1021/acs.jproteome.4c00724","DOIUrl":"10.1021/acs.jproteome.4c00724","url":null,"abstract":"Staphylococcus aureus is a leading cause of severe pneumonia. Our recent proteomic investigations into S. aureus invasion of human lung epithelial cells revealed three key adaptive responses: activation of the SigB and CodY regulons and upregulation of the hibernation-promoting factor SaHPF. Therefore, our present study aimed at a functional and proteomic dissection of the contributions of CodY, SigB and SaHPF to host invasion using transposon mutants of the methicillin-resistant S. aureus USA300. Interestingly, disruption of codY resulted in a \"small colony variant\" phenotype and redirected the bacteria from (phago)lysosomes into the host cell cytoplasm. Furthermore, we show that CodY, SigB and SaHPF contribute differentially to host cell adhesion, invasion, intracellular survival and cytotoxicity. CodY- or SigB-deficient bacteria experienced faster intracellular clearance than the parental strain, underscoring the importance of these regulators for intracellular persistence. We also show an unprecedented role of SaHPF in host cell adhesion and invasion. Proteomic analysis of the different mutants focuses attention on the CodY-perceived metabolic state of the bacteria and the SigB-perceived environmental cues in bacterial decision-making prior and during infection. Additionally, it underscores the impact of the nutritional status and bacterial stress on the initiation and progression of staphylococcal lung infections.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0