Global profiling of lysine 2-hydroxyisobutyrylome in Toxoplasma gondii using affinity purification mass spectrometry.

Global profiling of lysine 2-hydroxyisobutyrylome in Toxoplasma gondii using affinity purification mass spectrometry.
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使用亲和纯化质谱法对弓形虫中的赖氨酸 2-羟基异丁酰组进行整体分析。

DOI:
10.1007/s00436-020-06923-w
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发表时间:
2020
影响因子:
2
通讯作者:
Li Facai
Li Facai
中科院分区:
医学3区
文献类型:
--
作者:
Nie Lanbi;Liang Qinli;Elsheikha Hany M.;Du Rui;Zhu Xingquan;Li Facai

文献摘要

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赖氨酸2-羟基异丁酰化(Khib)是最近发现的一种在哺乳动物和酵母细胞中发现的进化上保守的蛋白质翻译后修饰(PTM)形式。已有研究表明,Khib在基因转录活性中发挥作用,含有Khib的蛋白与细胞代谢密切相关。在这项研究中,使用最新的数据库(ToxoDB 46,8322个序列,于2020年4月16日下载)和灵敏的免疫亲和富集结合液相色谱-串联质谱进行了全球含Khib分析。在刚地弓形虫RH株速殖子的400个含Khib蛋白质中共发现1078个Khib修饰位点。生物信息学和功能富集分析表明,Khib修饰的蛋白质与核糖体、糖酵解/糖异生、中心碳代谢等多种生物学过程相关。有趣的是,分泌细胞器的许多蛋白质(例如,微线体、棒状体和致密颗粒体)在T. gondii基因被Khib修饰,提示T.生殖道感染我们还发现,组蛋白,细胞代谢相关的关键酶,和几个滑体成分有Khibsites。这些结果扩展了我们对KhibinT作用的理解。弓形虫应促进对Khib如何调节弓形虫基因表达和关键生物学功能的进一步研究。
Lysine 2-hydroxyisobutyrylation (Khib) is a recently discovered and evolutionarily conserved form of protein post-translational modification (PTM) found in mammalian and yeast cells. Previous studies have shown that Khibplays roles in the activity of gene transcription and Khib-containing proteins are closely related to the cellular metabolism. In this study, a global Khib-containing analysis using the latest databases (ToxoDB 46, 8322 sequences, downloaded on April 16, 2020) and sensitive immune-affinity enrichment coupled with liquid chromatography-tandem mass spectrometry was performed. A total of 1078 Khibmodification sites across 400 Khib-containing proteins were identified in tachyzoites ofToxoplasma gondiiRH strain. Bioinformatics and functional enrichment analysis showed that Khib-modified proteins were associated with various biological processes, such as ribosome, glycolysis/gluconeogenesis, and central carbon metabolism. Interestingly, many proteins of the secretory organelles (e.g., microneme, rhoptry, and dense granule) that play roles in the infection cycle ofT. gondiiwere found to be Khib-modified, suggesting the involvement of Khibin key biological process duringT. gondiiinfection. We also found that histone proteins, key enzymes related to cellular metabolism, and several glideosome components had Khibsites. These results expanded our understanding of the roles of KhibinT. gondiiand should promote further investigations of how Khibregulates gene expression and key biological functions inT. gondii.