First Succinyl-Proteome Profiling of Extensively Drug-Resistant Mycobacterium tuberculosis Revealed Involvement of Succinylation in Cellular Physiology

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• 作者：Longxiang Xie ; Wei Liu ; Qiming Li ; Shudan Chen ; Mengmeng Xu ; Qinqin Huang ; Jie Zeng ; Mingliang Zhou ; Jianping Xie
• 刊名：Journal of Proteome Research
• 出版年：2015
• 出版时间：January 2, 2015
• 年：2015
• 卷：14
• 期：1
• 页码：107-119
• 全文大小：671K
• ISSN：1535-3907

文摘

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鈥揗S/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.