GNAT toxins evolve toward narrow tRNA target specificities.

GNAT toxins evolve toward narrow tRNA target specificities.
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DOI:
10.1093/nar/gkac356
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发表时间:
2022-06-10
影响因子:
14.9
通讯作者:
Dubiley, Svetlana
Dubiley, Svetlana
中科院分区:
生物学2区
文献类型:
--
作者:
Bikmetov, Dmitry;Hall, Alexander M. J.;Livenskyi, Alexei;Gollan, Bridget;Ovchinnikov, Stepan;Gilep, Konstantin;Kim, Jenny Y.;Larrouy-Maumus, Gerald;Zgoda, Viktor;Borukhov, Sergei;Severinov, Konstantin;Helaine, Sophie;Dubiley, Svetlana

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Ⅱ型毒素-抗毒素(TA)系统是广泛分布于原核生物中的双基因模块。与DUF 1778抗毒素相关的GNAT毒素代表了II型TA的大家族。GNAT毒素通过氨酰-tRNA的乙酰化破坏翻译来抑制细胞生长。在这项工作中,我们探索了GNAT毒素的进化轨迹。使用LC/MS检测乙酰化氨酰-tRNA结合核糖体分析,我们系统地研究了不同GNAT毒素阵列的体内底物特异性。我们的功能数据表明,大多数GNAT毒素是特异性的Gly-tRNA isoceptor。然而,系统发育分析表明,GNAT毒素的祖先可能是一个宽松的特异性酶,能够乙酰化多个延伸子tRNA。总之,我们的数据提供了一个显着的快照基板特异性的演变。
Type II toxin–antitoxin (TA) systems are two-gene modules widely distributed among prokaryotes. GNAT toxins associated with the DUF1778 antitoxins represent a large family of type II TAs. GNAT toxins inhibit cell growth by disrupting translation via acetylation of aminoacyl-tRNAs. In this work, we explored the evolutionary trajectory of GNAT toxins. Using LC/MS detection of acetylated aminoacyl-tRNAs combined with ribosome profiling, we systematically investigated the in vivo substrate specificity of an array of diverse GNAT toxins. Our functional data show that the majority of GNAT toxins are specific to Gly-tRNA isoacceptors. However, the phylogenetic analysis shows that the ancestor of GNAT toxins was likely a relaxed specificity enzyme capable of acetylating multiple elongator tRNAs. Together, our data provide a remarkable snapshot of the evolution of substrate specificity.
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