TmcA functions as a lysine 2-hydroxyisobutyryltransferase to regulate transcription

TmcA functions as a lysine 2-hydroxyisobutyryltransferase to regulate transcription
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TmcA 作为赖氨酸 2-羟基异丁酰转移酶来调节转录

DOI:
10.1038/s41589-021-00906-3
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发表时间:
2021-12-13
影响因子:
14.8
通讯作者:
Zhang, Kai
Zhang, Kai
中科院分区:
生物学1区
文献类型:
--
作者:
Dong, Hanyang;Zhao, Yujie;Zhang, Kai

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蛋白质赖氨酸2-羟基异丁酰化(Khib)最近已被证明在细胞过程的调节中发挥关键作用。然而,Khib在原核生物中的作用机制和功能后果仍不清楚。在这里,我们报告TmcA,RNA乙酰转移酶,功能作为赖氨酸2-羟基异丁酰转移酶的转录调节。我们发现,TmcA可以有效地催化Khib在体外和细胞内,R502是一个关键位点的Khib催化活性的TmcA。使用定量蛋白质组学,我们确定了467个内源性候选人靶向TmcA的Khib在大肠杆菌。有趣的是,我们证明,TmcA可以特异性地调节DNA结合活性的H-NS,一个核相关的蛋白质,通过催化K121的Khib。此外,这种TmcA靶向的Khib调节耐酸基因的转录,并增强E。大肠杆菌在酸胁迫下的存活率。我们的研究揭示了TmcA催化的Khib介导的细菌耐酸性的转录调控。
Protein lysine 2-hydroxyisobutyrylation (Khib) has recently been shown to play a critical role in the regulation of cellular processes. However, the mechanism and functional consequence of Khib in prokaryotes remain unclear. Here we report that TmcA, an RNA acetyltransferase, functions as a lysine 2-hydroxyisobutyryltransferase in the regulation of transcription. We show that TmcA can effectively catalyze Khib both in vitro and intracellularly, and that R502 is a key site for the Khib catalytic activity of TmcA. Using quantitative proteomics, we identified 467 endogenous candidates targeted by TmcA for Khib in Escherichia coli. Interestingly, we demonstrate that TmcA can specifically modulate the DNA-binding activity of H-NS, a nucleoid-associated protein, by catalysis of Khib at K121. Furthermore, this TmcA-targeted Khib regulates transcription of acid-resistance genes and enhances E. coli survival under acid stress. Our study reveals transcription regulation mediated by TmcA-catalyzed Khib for bacterial acid resistance.