2015年5月26日訊 /生物谷BIOON/-- 在2015年2月的The International Journal of Biochemistry & Cell Biology雜誌上，來自西南大學的研究人員發布了他們在結核桿菌賴氨酸乙醯化修飾研究的最新成果。
賴氨酸乙醯化是一種重要的蛋白質翻譯後修飾形式，它不僅可以改變DNA結合活性從而改變基因的表達，也可以調控蛋白-蛋白之間的相互作用，蛋白質的活性，mRNA的穩定性。研究表明，乙醯化在原核及真核生物都普遍存在，調控多種重要的生物進程，具有高度保守。
結核桿菌Mycobacterium tuberculosis (Mtb)是肺結核(TB)的病原菌，人類公共健康的強大威脅成員之一。全球每年有900萬新結核感染病例，約160萬例死亡。已有研究表明結核桿菌中賴氨酸乙醯化蛋白的存在，因此推測結核桿菌蛋白質組中含有更多不為人知的乙醯化蛋白。。
研究人員通過高解析度的質譜分析結合乙醯化多肽的免疫親和富集，鑑定到1128個乙醯化位點的存在，共計位於658個乙醯化的結核桿菌蛋白上， 是目前在細菌體內鑑定到的乙醯化蛋白最高記錄。GO分析表明這些乙醯化蛋白參與調控多種細胞進程包括代謝及蛋白質合成。結核桿菌中鑑定到的20個乙醯化蛋白在大腸桿菌、沙門氏菌、枯草芽孢桿菌和鏈黴素菌中均有同源性，其中一些乙醯化位點在這幾種細菌中存在高度保守性，這再次印證了已有研究。
值得注意的是，結核桿菌中一些參與持久性、毒性和抗生素耐藥性的蛋白包括異檸檬酸裂解酶（結核桿菌中乙醛酸循環的核心成分）存在乙醯化。而將異檸檬酸裂解酶乙醯化位點定點突變為穀氨酸後則會造成酶活性的降低，表明這些蛋白的乙醯化位點參與細胞進程的重要作用。
本研究結果首次提供了結合桿菌中乙醯化的全譜，為該病原菌中乙醯化廣泛的調控作用提供了線索。同時也可以作為研究賴氨酸乙醯化在結核桿菌代謝，持續力和毒性的基礎。（生物谷Bioon.com）
2015蛋白質修飾與降解論壇邀請該領域的國內專家，著重討論自噬、凋亡、壞死性凋亡的調控與泛素化系統，生物製藥與糖基化，細胞信號轉導與磷酸化，感染、炎症、免疫反應中的蛋白修飾與降解，幹細胞更新以及發育過程中的蛋白修飾與降解、不同蛋白修飾系統的交互作用、溶酶體蛋白功能與蛋白降解等，同時也會交流蛋白修飾與降解研究所帶來的新的疾病治療手段。
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生物谷推薦的原文閱讀：
Proteome-wide lysine acetylation profiling of the human pathogen Mycobacterium tuberculosis.
N(?)-Acetylation of lysine residues represents a pivotal post-translational modification used by both eukaryotes and prokaryotes to modulate diverse biological processes. Mycobacterium tuberculosis is the causative agent of tuberculosis, one of the most formidable public health threats. Many aspects of the biology of M. tuberculosis remain elusive, in particular the extent and function of N(?)-lysine acetylation. With a combination of anti-acetyllysine antibody-based immunoaffinity enrichment with high-resolution mass spectrometry, we identified 1128 acetylation sites on 658 acetylated M. tuberculosis proteins. GO analysis of the acetylome showed that acetylated proteins are involved in the regulation of diverse cellular processes including metabolism and protein synthesis. Six types of acetylated peptide sequence motif were revealed from the acetylome. Twenty lysine-acetylated proteins showed homology with acetylated proteins previously identified from Escherichia coli, Salmonella enterica, Bacillus subtilis and Streptomyces roseosporus, with several acetylation sites highly conserved among four or five bacteria, suggesting that acetylated proteins are more conserved. Notably, several proteins including isocitrate lyase involved in the persistence, virulence and antibiotic resistance are acetylated, and site-directed mutagenesis of isocitrate lyase acetylation site to glutamine led to a decrease of the enzyme activity, indicating major roles of KAc in these proteins engaged cellular processes. Our data firstly provides a global survey of M. tuberculosis acetylation, and implicates extensive regulatory role of acetylation in this pathogen. This may serve as an important basis to address the roles of lysine acetylation in M. tuberculosis metabolism, persistence and virulence.