期刊
NUCLEIC ACIDS RESEARCH
卷 50, 期 10, 页码 5807-5817出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkac356
关键词
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资金
- National Institutes ofHealth [RO1AI155552]
- Ministry of Science and Higher Education of the Russian Federation [RO1AI155552, 075-15-2019-1661, 075-10-2021-114]
This study explores the evolutionary trajectory of GNAT toxins and systematically investigates their substrate specificity using experimental data. The majority of GNAT toxins were found to be specific to Gly-tRNA isoacceptors.
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 acety-lating multiple elongator tRNAs. Together, our data provide a remarkable snapshot of the evolution of substrate specificity.
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