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Mechanism of translation inhibition by type II GNAT toxin AtaT2.
Nucleic Acids Res. 2020 Jun 29 [Online ahead of print]NA

Abstract

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.

Authors+Show Affiliations

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. Institute of Gene Biology, Russian Academy of Science, 119334 Moscow, Russia.Institute of Gene Biology, Russian Academy of Science, 119334 Moscow, Russia. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119992, Russia.Institute of Gene Biology, Russian Academy of Science, 119334 Moscow, Russia. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.Centre for Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia.Center for Biomolecular Sciences, University of Illinois, Chicago, IL 60607, USA. Department of Pharmaceutical Sciences, University of Illinois, Chicago, IL 60607, USA.Department of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia.Centre for Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia. Department of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia.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.Department of Cell Biology and Neuroscience, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084-1489, USA.Center for Biomolecular Sciences, University of Illinois, Chicago, IL 60607, USA. Department of Pharmaceutical Sciences, University of Illinois, Chicago, IL 60607, USA.Center for Biomolecular Sciences, University of Illinois, Chicago, IL 60607, USA. Department of Pharmaceutical Sciences, University of Illinois, Chicago, IL 60607, USA.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.Centre for Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia. Institute of Gene Biology, Russian Academy of Science, 119334 Moscow, Russia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32597957

Citation

Ovchinnikov, Stepan V., et al. "Mechanism of Translation Inhibition By Type II GNAT Toxin AtaT2." Nucleic Acids Research, 2020.
Ovchinnikov SV, Bikmetov D, Livenskyi A, et al. Mechanism of translation inhibition by type II GNAT toxin AtaT2. Nucleic Acids Res. 2020.
Ovchinnikov, S. V., Bikmetov, D., Livenskyi, A., Serebryakova, M., Wilcox, B., Mangano, K., Shiriaev, D. I., Osterman, I. A., Sergiev, P. V., Borukhov, S., Vazquez-Laslop, N., Mankin, A. S., Severinov, K., & Dubiley, S. (2020). Mechanism of translation inhibition by type II GNAT toxin AtaT2. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa551
Ovchinnikov SV, et al. Mechanism of Translation Inhibition By Type II GNAT Toxin AtaT2. Nucleic Acids Res. 2020 Jun 29; PubMed PMID: 32597957.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanism of translation inhibition by type II GNAT toxin AtaT2. AU - Ovchinnikov,Stepan V, AU - Bikmetov,Dmitry, AU - Livenskyi,Alexei, AU - Serebryakova,Marina, AU - Wilcox,Brendan, AU - Mangano,Kyle, AU - Shiriaev,Dmitrii I, AU - Osterman,Ilya A, AU - Sergiev,Petr V, AU - Borukhov,Sergei, AU - Vazquez-Laslop,Nora, AU - Mankin,Alexander S, AU - Severinov,Konstantin, AU - Dubiley,Svetlana, Y1 - 2020/06/29/ PY - 2020/06/17/accepted PY - 2020/06/05/revised PY - 2020/04/12/received PY - 2020/6/30/entrez JF - Nucleic acids research JO - Nucleic Acids Res. N2 - 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. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/32597957/Mechanism_of_translation_inhibition_by_type_II_GNAT_toxin_AtaT2 L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkaa551 DB - PRIME DP - Unbound Medicine ER -
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