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在2015年2月的The International Journal of Biochemistry & Cell Biology杂志上，来自西南大学的研究人员发布了他们在结核杆菌赖氨酸乙酰化修饰研究的最新成果。
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赖氨酸乙酰化是一种重要的蛋白质翻译后修饰形式，它不仅可以改变DNA结合活性从而改变基因的表达，也可以调控蛋白-蛋白之间的相互作用，蛋白质的活性，mRNA的稳定性。研究表明，乙酰化在原核及真核生物都普遍存在，调控多种重要的生物进程，具有高度保守。 结核杆菌Mycobacterium tuberculosis(Mtb)是肺结核(TB)的病原菌，人类公共健康的强大威胁成员之一。全球每年有900万新结核感染病例，约160万例死亡。已有研究表明结核杆菌中赖氨酸乙酰化蛋白的存在，因此推测结核杆菌蛋白质组中含有更多不为人知的乙酰化蛋白。 研究人员通过高分辨率的质谱分析结合乙酰化多肽的免疫亲和富集，鉴定到1128个乙酰化位点的存在，共计位于658个乙酰化的结核杆菌蛋白上，是目前在细菌体内鉴定到的乙酰化蛋白最高记录。GO分析表明这些乙酰化蛋白参与调控多种细胞进程包括代谢及蛋白质合成。结核杆菌中鉴定到的20个乙酰化蛋白在大肠杆菌、沙门氏菌、枯草芽孢杆菌和链霉素菌中均有同源性，其中一些乙酰化位点在这几种细菌中存在高度保守性，这再次印证了已有研究。 值得注意的是，结核杆菌中一些参与持久性、毒性和抗生素耐药性的蛋白包括异柠檬酸裂解酶（结核杆菌中乙醛酸循环的核心成分）存在乙酰化。而将异柠檬酸裂解酶乙酰化位点定点突变为谷氨酸后则会造成酶活性的降低，表明这些蛋白的乙酰化位点参与细胞进程的重要作用。 本研究结果首次提供了结合杆菌中乙酰化的全谱，为该病原菌中乙酰化广泛的调控作用提供了线索。同时也可以作为研究赖氨酸乙酰化在结核杆菌代谢，持续力和毒性的基础。 原文链接：Proteome-wide lysine acetylation profiling of the human pathogen Mycobacterium tuberculosis. N(ɛ)-Acetylation of lysine residues represents a pivotalpost-translational modification used by both eukaryotes and prokaryotesto modulate diverse biological processes. Mycobacterium tuberculosis isthe causative agent of tuberculosis, one of the most formidable publichealth threats. Many aspects of the biology of M. tuberculosis remainelusive, in particular the extent and function ofN(ɛ)-lysine acetylation. With a combination of anti-acetyllysineantibody-based immunoaffinity enrichment with high-resolution massspectrometry, we identified 1128 acetylation sites on 658 acetylated M.tuberculosis proteins. GO analysis of the acetylome showed thatacetylated proteins are involved in the regulation of diverse cellularprocesses including metabolism and protein synthesis. Six types ofacetylated peptide sequence motif were revealed from the acetylome.Twentylysine-acetylated proteins showed homology with acetylatedproteins previously identified from Escherichia coli, Salmonellaenterica, Bacillus subtilis and Streptomyces roseosporus, withseveral acetylation sites highly conserved among four or five bacteria,suggesting that acetylated proteins are more conserved. Notably, severalproteins including isocitratelyase involved in the persistence,virulence and antibiotic resistance are acetylated, and site-directedmutagenesis of isocitratelyase acetylation site to glutamine led to adecrease of the enzyme activity, indicating major roles of KAc in theseproteins engaged cellular processes. Our data firstly provides a globalsurvey of M. tuberculosis acetylation, and implicates extensiveregulatory role of acetylation in this pathogen. This may serve as animportant basis to address the roles of lysine acetylation in M.tuberculosis metabolism, persistence and virulence. |
