title: First succinyl-proteome profiling of extensively drug-resistant Mycobacterium tuberculosis revealed involvement of succinylation in cellular physiology.
abstract: Protein lysine succinylation, an emerging protein post-translational modification widespread among eukaryotic and prokaryotic cells, represents an important regulator of cellular processes. However, the extent and function of lysine succinylation in Mycobacterium tuberculosis, especially extensively drug-resistant strain, remain elusive. Combining protein/peptide prefractionation, immunoaffinity enrichment, and LC-MS/MS analysis, a total of 686 succinylated proteins and 1739 succinylation sites of M. tuberculosis were identified, representing the first global profiling of M. tuberculosis lysine succinylation. The identified succinylated proteins are involved in a variety of cellular functions such as metabolic processes, transcription, translation, and stress responses and exhibit different subcellular localization via GO, protein interaction network, and other bioinformatic analysis. Notably, proteins involved in protein biosynthesis and carbon metabolism are preferred targets of lysine succinylation. Moreover, two prevalent sequence patterns: EK(suc) and K*****K(suc), can be found around the succinylation sites. There are 109 lysine-succinylated homologues in E. coli, suggesting highly conserved succinylated proteins. Succinylation was found to occur at the active sites predicted by Prosite signature including Rv0946c, indicating that lysine succinylation may affect their activities. There is extensive overlapping between acetylation sites and succinylation sites in M. tuberculosis. Many M. tuberculosis metabolic enzymes and antibiotic resistance proteins were succinylated. This study provides a basis for further characterization of the pathophysiological role of lysine succinylation in M. tuberculosis.
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University , Beibei, Chongqing 400715, China.
authors.forename: Longxiang
authors.initials: L
authors.lastname: Xie
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Qiming
authors.initials: Q
authors.lastname: Li
authors.forename: Shudan
authors.initials: S
authors.lastname: Chen
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Xu
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Zeng
authors.forename: Mingliang
authors.initials: M
authors.lastname: Zhou
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D024901:Drug Resistance, Multiple, Bacterial; D053858:Metabolic Networks and Pathways; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D060066:Protein Interaction Maps; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D013386:Succinates / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D013386:Succinates
keywords: antibiotic resistance; extensively drug-resistant (XDR); lysine succinylation; metabolism; multi-drug-resistant (MDR); posttranslational modification