Succinylome Analysis Reveals the Involvement of Lysine Succinylation in Metabolism in Pathogenic Mycobacterium tuberculosis

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	Succinylome Analysis Reveals the Involvement of Lysine Succinylation in Metabolism in Pathogenic Mycobacterium tuberculosis
	Yang, Mingkun 1; Wang, Yan 1; Chen, Ying 1; Cheng, Zhongyi 2; Gu, Jing 3; Deng, Jiaoyu 3; Bi, Lijun 4; Chen, Chuangbin 5; Mo, Ran 1; Wang, Xude 3
刊名	MOLECULAR & CELLULAR PROTEOMICS
	2015-04-01
卷号	14 期号:4 页码:796-811
ISSN号	1535-9476
通讯作者	Ge, F (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China.
英文摘要	Mycobacterium 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.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biochemical Research Methods
研究领域[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	ACETYL-COA SYNTHETASE ; PARTICLE MESH EWALD ; LARGE GENE LISTS ; POSTTRANSLATIONAL MODIFICATIONS ; PHOSPHOPROTEOME ANALYSIS ; CARBON METABOLISM ; PROTEIN ACYLATION ; ESCHERICHIA-COLI ; DRUG-RESISTANCE ; IDENTIFICATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000352194400001
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/23981]
专题	水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文
作者单位	1.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
推荐引用方式 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, Feng.(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.