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Succinylome Analysis Reveals the Involvement of Lysine Succinylation in Metabolism in Pathogenic Mycobacterium tuberculosis
Yang, Mingkun1; Wang, Yan1; Chen, Ying1; Cheng, Zhongyi2; Gu, Jing3; Deng, Jiaoyu3; Bi, Lijun4; Chen, Chuangbin5; Mo, Ran1; Wang, Xude3; Ge, Feng1; Ge, F (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China.
2015-04-01
Source PublicationMOLECULAR & CELLULAR PROTEOMICS
ISSN1535-9476
Volume14Issue:4Pages:796-811
AbstractMycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, remains one of the most prevalent human pathogens and a major cause of mortality worldwide. Metabolic network is a central mediator and defining feature of the pathogenicity of Mtb. Increasing evidence suggests that lysine succinylation dynamically regulates enzymes in carbon metabolism in both bacteria and human cells; however, its extent and function in Mtb remain unexplored. Here, we performed a global succinylome analysis of the virulent Mtb strain H37Rv by using high accuracy nano-LC-MS/MS in combination with the enrichment of succinylated peptides from digested cell lysates and subsequent peptide identification. In total, 1545 lysine succinylation sites on 626 proteins were identified in this pathogen. The identified succinylated proteins are involved in various biological processes and a large proportion of the succinylation sites are present on proteins in the central metabolism pathway. Site-specific mutations showed that succinylation is a negative regulatory modification on the enzymatic activity of acetylCoA synthetase. Molecular dynamics simulations demonstrated that succinylation affects the conformational stability of acetyl-CoA synthetase, which is critical for its enzymatic activity. Further functional studies showed that CobB, a sirtuin-like deacetylase in Mtb, functions as a desuccinylase of acetyl-CoA synthetase in in vitro assays. Together, our findings reveal widespread roles for lysine succinylation in regulating metabolism and diverse processes in Mtb. Our data provide a rich resource for functional analyses of lysine succinylation and facilitate the dissection of metabolic networks in this life-threatening pathogen.
SubtypeArticle
Department[Yang, Mingkun ; Wang, Yan ; Chen, Ying ; Mo, Ran ; Ge, Feng] Chinese Acad Sci, Inst Hydrobiol, Key Lab Algal Biol, Wuhan 430072, Peoples R China ; [Cheng, Zhongyi] Tongji Univ, Adv Inst Translat Med, Shanghai 200092, Peoples R China ; [Gu, Jing ; Deng, Jiaoyu ; Wang, Xude] Chinese Acad Sci, Wuhan Inst Virol, Wuhan 430071, Peoples R China ; [Bi, Lijun] Chinese Acad Sci, Inst Biophys, Key Lab Noncoding RNA, Beijing 100101, Peoples R China ; [Chen, Chuangbin] Jingjie PTM Biolabs Hangzhou Co Ltd, Hangzhou 310018, Zhejiang, Peoples R China
DOI10.1074/mcp.M114.045922
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemical Research Methods
WOS IDWOS:000352194400001
WOS KeywordACETYL-COA SYNTHETASE ; PARTICLE MESH EWALD ; LARGE GENE LISTS ; POSTTRANSLATIONAL MODIFICATIONS ; PHOSPHOPROTEOME ANALYSIS ; CARBON METABOLISM ; PROTEIN ACYLATION ; ESCHERICHIA-COLI ; DRUG-RESISTANCE ; IDENTIFICATION
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Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/23981
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorGe, F (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China.
Affiliation1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Algal Biol, Wuhan 430072, Peoples R China
2.Tongji Univ, Adv Inst Translat Med, Shanghai 200092, Peoples R China
3.Chinese Acad Sci, Wuhan Inst Virol, Wuhan 430071, Peoples R China
4.Chinese Acad Sci, Inst Biophys, Key Lab Noncoding RNA, Beijing 100101, Peoples R China
5.Jingjie PTM Biolabs Hangzhou Co Ltd, Hangzhou 310018, Zhejiang, Peoples R China
Recommended Citation
GB/T 7714
Yang, Mingkun,Wang, Yan,Chen, Ying,et al. Succinylome Analysis Reveals the Involvement of Lysine Succinylation in Metabolism in Pathogenic Mycobacterium tuberculosis[J]. MOLECULAR & CELLULAR PROTEOMICS,2015,14(4):796-811.
APA Yang, Mingkun.,Wang, Yan.,Chen, Ying.,Cheng, Zhongyi.,Gu, Jing.,...&Ge, F .(2015).Succinylome Analysis Reveals the Involvement of Lysine Succinylation in Metabolism in Pathogenic Mycobacterium tuberculosis.MOLECULAR & CELLULAR PROTEOMICS,14(4),796-811.
MLA Yang, Mingkun,et al."Succinylome Analysis Reveals the Involvement of Lysine Succinylation in Metabolism in Pathogenic Mycobacterium tuberculosis".MOLECULAR & CELLULAR PROTEOMICS 14.4(2015):796-811.
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