AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet
AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet
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DOI：
10.1038/nchembio.2346
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发表时间：
2017-06-01
影响因子：
14.8
通讯作者：
Van Melderen, Laurence
中科院分区：
文献类型：
--
作者：
Jurenas, Dukas;Chatterjee, Sneha;Van Melderen, Laurence
毒素-抗毒素（TA）基因座普遍存在于细菌基因组中。它们被认为在休眠和持续状态中起着核心作用。在正常生长条件下，TA毒素被其同源抗毒素中和，在应激条件下，毒素被释放并使用多种机制抑制基本细胞过程。在这里，我们表征ataR-ataT，一种新的TA系统，从肠出血性大肠杆菌。我们表明，毒素AtaT是一个GNAT家族酶，转移乙酰基从乙酰辅酶A的氨基的甲硫氨酰氨基酰基部分的引发剂tRNA的乙酰基。AtaT特异性修饰Met-tRNA（fMet），但不修饰其他氨酰-tRNA，包括延伸子Met-tRNAMet。我们证明，一旦乙酰化，AcMet-tRNA（fMet）未能与起始因子-2（IF 2）相互作用，导致翻译起始复合物的破坏。这项工作揭示了一种新的翻译抑制机制，并证实Met-tRNA（fMet）是有效阻断细胞生长的主要靶点。
Toxin-antitoxin (TA) loci are prevalent in bacterial genomes. They are suggested to play a central role in dormancy and persister states. Under normal growth conditions, TA toxins are neutralized by their cognate antitoxins, and under stress conditions, toxins are freed and inhibit essential cellular processes using a variety of mechanisms. Here we characterize ataR-ataT, a novel TA system, from enterohemorrhagic Escherichia coli. We show that the toxin AtaT is a GNAT family enzyme that transfers an acetyl group from acetyl coenzyme A to the amine group of the methionyl aminoacyl moiety of initiator tRNA. AtaT specifically modifies Met-tRNA(fMet), but no other aminoacyl-tRNAs, including the elongator Met-tRNAMet. We demonstrate that once acetylated, AcMet-tRNA(fMet) fails to interact with initiation factor-2 (IF2), resulting in disruption of the translation initiation complex. This work reveals a new mechanism of translation inhibition and confirms Met-tRNA(fMet) as a prime target to efficiently block cell growth.