Mechanism of translation inhibition by type II GNAT toxin AtaT2.

Autor:	Ovchinnikov SV; Centre for Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia., Bikmetov D; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.; Institute of Gene Biology, Russian Academy of Science, 119334 Moscow, Russia., Livenskyi A; Institute of Gene Biology, Russian Academy of Science, 119334 Moscow, Russia.; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119992, Russia., Serebryakova M; Institute of Gene Biology, Russian Academy of Science, 119334 Moscow, Russia.; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia., Wilcox B; Centre for Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia., Mangano K; Center for Biomolecular Sciences, University of Illinois, Chicago, IL 60607, USA.; Department of Pharmaceutical Sciences, University of Illinois, Chicago, IL 60607, USA., Shiriaev DI; Department of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia., Osterman IA; Centre for Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia.; Department of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia., Sergiev PV; Centre for Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia.; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia., Borukhov S; Department of Cell Biology and Neuroscience, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084-1489, USA., Vazquez-Laslop N; Center for Biomolecular Sciences, University of Illinois, Chicago, IL 60607, USA.; Department of Pharmaceutical Sciences, University of Illinois, Chicago, IL 60607, USA., Mankin AS; Center for Biomolecular Sciences, University of Illinois, Chicago, IL 60607, USA.; Department of Pharmaceutical Sciences, University of Illinois, Chicago, IL 60607, USA., Severinov K; Centre for Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.; Waksman Institute for Microbiology, Piscataway, NJ 08854-8020, USA., Dubiley S; Centre for Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia.; Institute of Gene Biology, Russian Academy of Science, 119334 Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2020 Sep 04; Vol. 48 (15), pp. 8617-8625.
DOI:	10.1093/nar/gkaa551
Abstrakt:	Type II toxin-antitoxins systems are widespread in prokaryotic genomes. Typically, they comprise two proteins, a toxin, and an antitoxin, encoded by adjacent genes and forming a complex in which the enzymatic activity of the toxin is inhibited. Under stress conditions, the antitoxin is degraded liberating the active toxin. Though thousands of various toxin-antitoxins pairs have been predicted bioinformatically, only a handful has been thoroughly characterized. Here, we describe the AtaT2 toxin from a toxin-antitoxin system from Escherichia coli O157:H7. We show that AtaT2 is the first GNAT (Gcn5-related N-acetyltransferase) toxin that specifically targets charged glycyl tRNA. In vivo, the AtaT2 activity induces ribosome stalling at all four glycyl codons but does not evoke a stringent response. In vitro, AtaT2 acetylates the aminoacyl moiety of isoaccepting glycyl tRNAs, thus precluding their participation in translation. Our study broadens the known target specificity of GNAT toxins beyond the earlier described isoleucine and formyl methionine tRNAs, and suggest that various GNAT toxins may have evolved to specificaly target other if not all individual aminoacyl tRNAs. (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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