Journal of Proteome Research最新文献_第2页

Comparative Metabolomics Reveals Changes in the Metabolic Pathways of Ampicillin- and Gentamicin-Resistant Staphylococcus aureus 比较代谢组学揭示耐氨苄西林和庆大霉素金黄色葡萄球菌代谢途径的变化

IF 4.4 2区生物学

Journal of Proteome Research Pub Date : 2024-09-18 DOI: 10.1021/acs.jproteome.4c00381

Ziyi Zhang, Zhiyu Pan, Lvyuan Fan, Yubin Su, Jiao Fei

{"title":"Comparative Metabolomics Reveals Changes in the Metabolic Pathways of Ampicillin- and Gentamicin-Resistant Staphylococcus aureus","authors":"Ziyi Zhang, Zhiyu Pan, Lvyuan Fan, Yubin Su, Jiao Fei","doi":"10.1021/acs.jproteome.4c00381","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00381","url":null,"abstract":"Antibiotic resistance is a major global challenge requiring new treatments and a better understanding of the bacterial resistance mechanisms. In this study, we compared ampicillin-resistant (R-AMP) and gentamicin-resistant (R-GEN) Staphylococcus aureus strains with a sensitive strain (ATCC6538) using metabolomics. We identified 109 metabolites; 28 or 31 metabolites in R-AMP or R-GEN differed from those in ATCC6538. Moreover, R-AMP and R-GEN were enriched in five and four pathways, respectively. R-AMP showed significantly up-regulated amino acid metabolism and down-regulated energy metabolism, whereas R-GEN exhibited an overall decrease in metabolism, including carbohydrate, energy, and amino acid metabolism. Furthermore, the activities of the metabolism-related enzymes pyruvate dehydrogenase and TCA cycle dehydrogenases were inhibited in antibiotic-resistant bacteria. Significant decreases in NADH and ATP levels were also observed. In addition, the arginine biosynthesis pathway, which is related to nitric oxide (NO) production, was enriched in both antibiotic-resistant strains. Enhanced NO synthase activity in S. aureus promoted NO production, which further reduced reactive oxygen species, mediating the development of bacterial resistance to ampicillin and gentamicin. This study reveals that bacterial resistance affects metabolic profile, and changes in energy metabolism and arginine biosynthesis are important factors leading to drug resistance in S. aureus.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264734","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

Proteomic Analysis Reveals Differential Protein Expression in Placental Tissues of Early-Onset Preeclampsia Patients 蛋白质组分析揭示早发型子痫前期患者胎盘组织中蛋白质表达的差异

IF 4.4 2区生物学

Journal of Proteome Research Pub Date : 2024-09-17 DOI: 10.1021/acs.jproteome.4c00404

Jun Zhou, Xiaoyu Hu, Ning Zhang, Yijing Chu, Junhuan Wang, Xuena Cui, Yan Zhang, Rendong Han, Chong Liu, Shengmei Yang, Jing Li

{"title":"Proteomic Analysis Reveals Differential Protein Expression in Placental Tissues of Early-Onset Preeclampsia Patients","authors":"Jun Zhou, Xiaoyu Hu, Ning Zhang, Yijing Chu, Junhuan Wang, Xuena Cui, Yan Zhang, Rendong Han, Chong Liu, Shengmei Yang, Jing Li","doi":"10.1021/acs.jproteome.4c00404","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00404","url":null,"abstract":"Preeclampsia, a significant cause of maternal and perinatal morbidity and mortality, remains poorly understood, in terms of its pathogenesis. This study aims to uncover novel and effective biomarkers for preeclampsia by conducting a comparative analysis of differential proteins in placentas from early onset preeclampsia (EOPE) and normal pregnancies. Utilizing tandem mass tag (TMT)-based quantitative proteomics, we identified differentially expressed proteins in placental tissues from 15 EOPE patients and 15 normal pregnant women. These proteins were subsequently validated by using parallel reaction monitoring (PRM). Our analysis revealed a total of 59 differentially expressed proteins, with 25 up-regulated and 34 down-regulated proteins in EOPE placental tissues compared to those from normal pregnancies. Validation through PRM confirmed the differential expression of 6 proteins. Our findings suggest these 6 proteins could play crucial roles in the pathogenesis of EOPE, highlighting the potential involvement of the estrogen signaling pathway and dilated cardiomyopathy (DCM) pathway in the development of preeclampsia. The data were deposited with the ProteomeXchange Consortium via the iProX partner repository with the identifier PXD055025.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264729","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

Characterizations of Protein Arginine Deiminase 1 as a Substrate of NTMT1: Implications of Nα-Methylation in Protein Stability and Interaction 蛋白精氨酸脱氨酶 1 作为 NTMT1 底物的特性：Nα-甲基化对蛋白质稳定性和相互作用的影响

IF 4.4 2区生物学

Journal of Proteome Research Pub Date : 2024-09-17 DOI: 10.1021/acs.jproteome.4c00484

Ying Meng, Zhouxian Li, Ming He, Quanqing Zhang, Youchao Deng, Yinsheng Wang, Rong Huang

{"title":"Characterizations of Protein Arginine Deiminase 1 as a Substrate of NTMT1: Implications of Nα-Methylation in Protein Stability and Interaction","authors":"Ying Meng, Zhouxian Li, Ming He, Quanqing Zhang, Youchao Deng, Yinsheng Wang, Rong Huang","doi":"10.1021/acs.jproteome.4c00484","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00484","url":null,"abstract":"α-N-Methylation (Nα-methylation), catalyzed by protein N-terminal methyltransferases (NTMTs), constitutes a crucial post-translational modification involving the transfer of a methyl group from S-adenosyl-l-methionine (SAM) to the Nα-terminal amino group of substrate proteins. NTMT1/2 are known to methylate canonical Nα sequences, such as X–P-K/R. With over 300 potential human protein substrates, only a small fraction has been validated, and even less is known about the functions of Nα-methylation. This study delves into the characterizations of protein arginine deiminase 1 (PAD1) as a substrate of NTMT1. By employing biochemical and cellular assays, we demonstrated NTMT1-mediated Nα-methylation of PAD1, leading to an increase in protein half-life and the modulation of protein–protein interactions in HEK293T cells. The methylation of PAD1 appears nonessential to its enzymatic activity or cellular localization. Proteomic studies revealed differential protein interactions between unmethylated and Nα-methylated PAD1, suggesting a regulatory role for Nα-methylation in modulating PAD1’s protein–protein interactions. These findings shed light on the intricate molecular mechanisms governing PAD1 function and expand our knowledge of Nα-methylation in regulating protein function.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264724","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

Influence of Software Settings on the Identification Rate, Quantification Results, and Reproducibility in Profiling Post-Translational Modifications by Microflow Liquid Chromatography–Ion Mobility-Quadrupole Time-Of-Flight Analysis Using PEAKS Software 使用 PEAKS 软件进行微流液相色谱-离子迁移率-四极杆飞行时间分析时，软件设置对翻译后修饰的识别率、定量结果和重现性的影响

IF 4.4 2区生物学

Journal of Proteome Research Pub Date : 2024-09-16 DOI: 10.1021/acs.jproteome.4c00207

Andreas Mauser, Sabrina Gensberger-Reigl, Sevim Dalabasmaz, Theresa Maria Schichtl, Daniel Dittrich, Monika Pischetsrieder

{"title":"Influence of Software Settings on the Identification Rate, Quantification Results, and Reproducibility in Profiling Post-Translational Modifications by Microflow Liquid Chromatography–Ion Mobility-Quadrupole Time-Of-Flight Analysis Using PEAKS Software","authors":"Andreas Mauser, Sabrina Gensberger-Reigl, Sevim Dalabasmaz, Theresa Maria Schichtl, Daniel Dittrich, Monika Pischetsrieder","doi":"10.1021/acs.jproteome.4c00207","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00207","url":null,"abstract":"The influence of data evaluation parameters on qualitative and quantitative results of untargeted shotgun profiling of enzymatic and nonenzymatic post-translational modifications (PTMs) was investigated in a model of bovine whey protein α-lactalbumin heated with lactose. Based on the same raw data, individual adjustments to the protein database and enzyme settings of PEAKS studio software increased the identification rate from 27 unmodified peptides to 48 and from 322 peptides in total to 535. The qualitative and quantitative reproducibility was also assessed based on 18 measurements of one sample across three batches. A total of 570 peptides were detected. While 89 peptides were identified in all measurements, the majority of peptides (161) were detected only once and mostly based on nonindicative spectra. The reproducibility of label-free quantification (LFQ) in six measurements of the same sample was similar after processing the data by either the PTM algorithm or the LFQ algorithm. In both cases, about one-third of the peptides showed a coefficient of variation of above 20%. However, the LFQ algorithm increased the number of quantified peptides from 75 to 179. Data are available at the PRIDE Archive with the data set identifier PXD050363.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264784","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

Combination of Metabolomics, Lipidomics, and Molecular Biology for the Investigation of the Metabolic Disturbance of Short-Term Administration of Emodin 结合代谢组学、脂质组学和分子生物学研究短期服用大黄素引起的代谢紊乱

IF 4.4 2区生物学

Journal of Proteome Research Pub Date : 2024-09-16 DOI: 10.1021/acs.jproteome.4c00313

Haitao Wang, Rui Mao, Liming Wang, Chenxi Wang, Tekleab Teka, Zixin Zhang, Shin Sik Choi, Zhifei Fu, Lifeng Han

{"title":"Combination of Metabolomics, Lipidomics, and Molecular Biology for the Investigation of the Metabolic Disturbance of Short-Term Administration of Emodin","authors":"Haitao Wang, Rui Mao, Liming Wang, Chenxi Wang, Tekleab Teka, Zixin Zhang, Shin Sik Choi, Zhifei Fu, Lifeng Han","doi":"10.1021/acs.jproteome.4c00313","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00313","url":null,"abstract":"Emodin, a natural anthraquinone derivative, is an active ingredient in many Chinese traditional herbs. Interestingly, although it is generally considered to possess hepatoprotective activity, some studies have also reported that it has a certain degree of hepatotoxicity. Additionally, the underlying metabolic regulation of emodin remains uncertain. Therefore, we conducted a nontargeted metabolomic study based on UHPLC/Q-Orbitrap-MS and NMR. Data are available via ProteomeXchange with the identifier PXD055000. The results indicated a close association between the short-term administration of emodin and lipid metabolism. Moreover, a lipidomics investigation utilizing QTRAP 6500+ UHPLC-MS/MS was conducted, with a focus on determining the position of C═C double bonds in unsaturated lipids based on Paternò–Büchi (PB) reaction to discover the metabolic disturbance more precisely. Specifically, lipidomics revealed elevated levels of free fatty acids (FFA) alongside notable reductions in sphingomyelin (SM) and triacylglycerol (TAG) levels. Furthermore, the combination of PB reaction and molecular biology results indicated that short-term administration of emodin may lead to the accumulation of n-6 polyunsaturated fatty acids by up-regulating the expression of FASN, stearyl CoA desaturase 1 (SCD1), and cytosolic phospholipase A 2 (cPLA2). Simultaneously, up-regulation of cyclooxygenase-2 (Cox-2) expression was observed, potentially fostering the production of prostaglandin E2 (PGE2) and subsequent inflammation.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264727","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

TMT-Based Quantitative Proteomics Revealed the Antibacterial Mechanism of Cinnamaldehyde against MRSA 基于 TMT 的定量蛋白质组学揭示了肉桂醛对 MRSA 的抗菌机制

IF 4.4 2区生物学

Journal of Proteome Research Pub Date : 2024-09-13 DOI: 10.1021/acs.jproteome.4c00520

Xiaohui Chen, Panpan Liu, Jingge Wang, Xiaoqiang He, Jianchong Wang, Haorong Chen, Guiqin Wang

{"title":"TMT-Based Quantitative Proteomics Revealed the Antibacterial Mechanism of Cinnamaldehyde against MRSA","authors":"Xiaohui Chen, Panpan Liu, Jingge Wang, Xiaoqiang He, Jianchong Wang, Haorong Chen, Guiqin Wang","doi":"10.1021/acs.jproteome.4c00520","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00520","url":null,"abstract":"Natural plant extracts have demonstrated significant potential in alternative antibiotic therapies. Cinnamaldehyde (CA) has garnered considerable attention as a natural antibacterial agent. In this study, Tandem mass tag (TMT) quantitative proteomics combined with Western blot and RT-qPCR methods were employed to explore the antibacterial mechanism of CA against Methicillin-Resistant Staphylococcus aureus (MRSA) at the protein level. The results showed that a total of 254 differentially expressed proteins (DEPs) were identified in the control group and CA treatment group, of which 161 were significantly upregulated and 93 were significantly downregulated. DEPs related to nucleotide synthesis, homeostasis of the internal environment, and protein biosynthesis were significantly upregulated, while DEPs involved in the cell wall, cell membrane, and virulence factors were significantly downregulated. The results of GO and KEGG enrichment analyses demonstrated that CA could exert its antibacterial effects by influencing pyruvate metabolism, the tricarboxylic acid (TCA) cycle, teichoic acid biosynthesis, and the Staphylococcus aureus (S. aureus) infection pathway in MRSA. CA significantly inhibited the expression of recombinant protein MgrA (p < 0.05), significantly reduced the mRNA transcription levels of mgrA, hla, and sdrD genes (p < 0.05), and thermostability migration assays demonstrated that CA can directly interact with MgrA protein, thereby inhibiting its activity. These findings suggest that CA exerts its antibacterial mechanism by regulating the expression of related proteins, providing a theoretical basis for further development of clinical applications of antimicrobial agents derived from natural plant essential oils in the treatment of dairy cow mastitis.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264728","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

Proteogenomic Characterization of Early Intrahepatic Recurrence after Curative-Intent Treatment of Colorectal Liver Metastases 结直肠癌肝转移治愈性治疗后早期肝内复发的蛋白质基因组特征描述

IF 4.4 2区生物学

Journal of Proteome Research Pub Date : 2024-09-12 DOI: 10.1021/acs.jproteome.4c00440

Geoffrey Yuet Mun Wong, Jun Li, Matthew McKay, Miguel Castaneda, Nazim Bhimani, Connie Diakos, Thomas J. Hugh, Mark P. Molloy

{"title":"Proteogenomic Characterization of Early Intrahepatic Recurrence after Curative-Intent Treatment of Colorectal Liver Metastases","authors":"Geoffrey Yuet Mun Wong, Jun Li, Matthew McKay, Miguel Castaneda, Nazim Bhimani, Connie Diakos, Thomas J. Hugh, Mark P. Molloy","doi":"10.1021/acs.jproteome.4c00440","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00440","url":null,"abstract":"Clinical and pathological factors are insufficient to accurately identify patients at risk of early recurrence after curative-intent treatment of colorectal liver metastases (CRLM). This study aimed to identify candidate prognostic proteogenomic biomarkers for early intrahepatic recurrence after curative-intent resection of CRLM. Patients diagnosed with intrahepatic recurrence within 6 months of liver resection were categorized as the “early recurrence” group, while those who achieved a recurrence-free status for 10 years were designated as “durable remission”. Comprehensive genomic and proteomic profiling of fresh frozen samples from these prognostically distinct groups was performed using the TruSight Oncology 500 assay and label-free data-dependent acquisition liquid chromatography–mass spectrometry. Genetic alterations were identified in 117 of the 523 profiled genes in patients with early recurrence. The most common somatic mutations linked to early recurrence were TP53 (88%), APC (71%), KRAS (38%), and SMAD4 (21%). SMAD4 alterations were absent in samples from patients with a durable remission. Calponin-2, versican core protein, glutathione peroxidase 3, fibulin-5, and amyloid-β precursor protein were upregulated more than 2-fold in early recurrence. Exploratory analysis of these proteogenomic biomarkers suggests that SMAD4, calponin-2, and glutathione peroxidase 3 may have the potential to predict early recurrence, enabling improved prognostication and precision oncology in CRLM.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179225","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

Role of Deoxyribonucleic Acid Origami for Alleviating Kidney and Liver Injury in Diabetic Sepsis 脱氧核糖核酸折纸在缓解糖尿病败血症肝肾损伤中的作用

IF 4.4 2区生物学

Journal of Proteome Research Pub Date : 2024-09-12 DOI: 10.1021/acs.jproteome.4c00543

Xinmei Luo, Wenshu Dai, Tianhai Lin, Ling Li, Yong Zhang

{"title":"Role of Deoxyribonucleic Acid Origami for Alleviating Kidney and Liver Injury in Diabetic Sepsis","authors":"Xinmei Luo, Wenshu Dai, Tianhai Lin, Ling Li, Yong Zhang","doi":"10.1021/acs.jproteome.4c00543","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00543","url":null,"abstract":"Treating diabetic sepsis (DS) can be challenging because of the persistent infection of multiple organs. To address this complicated pathological condition, it is necessary to develop advanced materials and gain a better understanding of their roles. In this study, we developed a two-dimensional planar material with a rectangular deoxyribonucleic acid origami nanostructure (termed Rec-DON). Rec-DON was used to improve liver and renal function in DS mice, as it preferentially accumulates in these organs, and has superior anti-inflammatory activity and the ability to scavenge reactive oxygen species. The role of Rec-DON in the treatment of DS mice was investigated via quantitative proteomics. This study revealed that Rec-DON can regulate key proteins located primarily in the cytoplasm and mitochondrion, involved in protein transport, antigen processing and presentation, and steroid metabolic process, and can also bind to various proteins to restore liver and renal function in DS mice. This study presented Rec-DON as a liver and kidney targeting material and revealed its role in alleviating multiorgan injury in DS.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179213","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

Analysis of Complexome Profiles with the Gaussian Interaction Profiler (GIP) Reveals Novel Protein Complexes in Plasmodium falciparum 用高斯相互作用剖析器（GIP）分析复合物组图谱，揭示恶性疟原虫中的新型蛋白质复合物

IF 4.4 2区生物学

Journal of Proteome Research Pub Date : 2024-09-12 DOI: 10.1021/acs.jproteome.4c00414

Joeri van Strien, Felix Evers, Alfredo Cabrera-Orefice, Iris Delhez, Taco W. A. Kooij, Martijn A. Huynen

{"title":"Analysis of Complexome Profiles with the Gaussian Interaction Profiler (GIP) Reveals Novel Protein Complexes in Plasmodium falciparum","authors":"Joeri van Strien, Felix Evers, Alfredo Cabrera-Orefice, Iris Delhez, Taco W. A. Kooij, Martijn A. Huynen","doi":"10.1021/acs.jproteome.4c00414","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00414","url":null,"abstract":"Complexome profiling is an experimental approach to identify interactions by integrating native separation of protein complexes and quantitative mass spectrometry. In a typical complexome profile, thousands of proteins are detected across typically ≤100 fractions. This relatively low resolution leads to similar abundance profiles between proteins that are not necessarily interaction partners. To address this challenge, we introduce the Gaussian Interaction Profiler (GIP), a Gaussian mixture modeling-based clustering workflow that assigns protein clusters by modeling the migration profile of each cluster. Uniquely, the GIP offers a way to prioritize actual interactors over spuriously comigrating proteins. Using previously analyzed human fibroblast complexome profiles, we show good performance of the GIP compared to other state-of-the-art tools. We further demonstrate GIP utility by applying it to complexome profiles from the transmissible lifecycle stage of malaria parasites. We unveil promising novel associations for future experimental verification, including an interaction between the vaccine target Pfs47 and the hypothetical protein PF3D7_0417000. Taken together, the GIP provides methodological advances that facilitate more accurate and automated detection of protein complexes, setting the stage for more varied and nuanced analyses in the field of complexome profiling. The complexome profiling data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD050751.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142179224","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

Proteome and Metabolome Profiling of Anticoagulant Disorders Induced by Familial Protein S Deficiency 家族性蛋白 S 缺乏症诱发的抗凝紊乱的蛋白质组和代谢组图谱分析

IF 4.4 2区生物学

Journal of Proteome Research Pub Date : 2024-09-12 DOI: 10.1021/acs.jproteome.4c00399

Caiping Zhang, Yimin Zhang, Binjie Liu, Yongxv Chen, Yue Xie, Huiting Huang, Zhongqiu Liu, Zhuoru He

{"title":"Proteome and Metabolome Profiling of Anticoagulant Disorders Induced by Familial Protein S Deficiency","authors":"Caiping Zhang, Yimin Zhang, Binjie Liu, Yongxv Chen, Yue Xie, Huiting Huang, Zhongqiu Liu, Zhuoru He","doi":"10.1021/acs.jproteome.4c00399","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00399","url":null,"abstract":"Protein S deficiency (PSD) is an autosomal dominant disorder characterized by congenital thrombophilia. Studies on PSD are limited yet, resulting in a lack of clarity about molecular changes during abnormal coagulation. Proteomics and metabolomics analyses were conducted on the plasma of PSD patients based on liquid and gas chromatography–mass spectrometry (LC- and GC–MS). Differential proteins and metabolites of PSD were then filtered by univariate statistical analysis and subjected to network analysis using the ingenuity pathway analysis (IPA) platform. The proteome and metabolome of PSD were obviously disturbed, and the biological pathway of coagulation and complement cascades was the most affected. During PSD, overall levels of anticoagulant protein decreased and negative regulation of thrombin production was reduced, causing the formation of fibrin clots and platelet aggregation. Furthermore, 9 differential proteins correlated significantly with protein S, comprising A2M, AGT, APOE, FGG, GPLD1, IGHV1–69, CFHR5, CPN2, and CA1. The biological networks suggested that the pathways of acute phase response, FXR/RXR activation, serotonin receptor signaling, and p70S6K signaling were associated with PSD, indicating an interaction disorder of inflammatory immune and lipid metabolism. The findings may contribute to knowledge of available functional molecules and biological pathways of familial PSD and help with treatment improvement. Data are available via ProteomeXchange with identifier PXD055111 and MetaboLights with reference number MTBLS2653.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264782","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