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Mechanism of translation inhibition by type II GNAT toxin AtaT2
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 libe...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470980/ https://www.ncbi.nlm.nih.gov/pubmed/32597957 http://dx.doi.org/10.1093/nar/gkaa551 |
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author | Ovchinnikov, Stepan V Bikmetov, Dmitry Livenskyi, Alexei Serebryakova, Marina Wilcox, Brendan Mangano, Kyle Shiriaev, Dmitrii I Osterman, Ilya A Sergiev, Petr V Borukhov, Sergei Vazquez-Laslop, Nora Mankin, Alexander S Severinov, Konstantin Dubiley, Svetlana |
author_facet | Ovchinnikov, Stepan V Bikmetov, Dmitry Livenskyi, Alexei Serebryakova, Marina Wilcox, Brendan Mangano, Kyle Shiriaev, Dmitrii I Osterman, Ilya A Sergiev, Petr V Borukhov, Sergei Vazquez-Laslop, Nora Mankin, Alexander S Severinov, Konstantin Dubiley, Svetlana |
author_sort | Ovchinnikov, Stepan V |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7470980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74709802020-09-09 Mechanism of translation inhibition by type II GNAT toxin AtaT2 Ovchinnikov, Stepan V Bikmetov, Dmitry Livenskyi, Alexei Serebryakova, Marina Wilcox, Brendan Mangano, Kyle Shiriaev, Dmitrii I Osterman, Ilya A Sergiev, Petr V Borukhov, Sergei Vazquez-Laslop, Nora Mankin, Alexander S Severinov, Konstantin Dubiley, Svetlana Nucleic Acids Res RNA and RNA-protein complexes 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. Oxford University Press 2020-09-04 2020-06-29 /pmc/articles/PMC7470980/ /pubmed/32597957 http://dx.doi.org/10.1093/nar/gkaa551 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | RNA and RNA-protein complexes Ovchinnikov, Stepan V Bikmetov, Dmitry Livenskyi, Alexei Serebryakova, Marina Wilcox, Brendan Mangano, Kyle Shiriaev, Dmitrii I Osterman, Ilya A Sergiev, Petr V Borukhov, Sergei Vazquez-Laslop, Nora Mankin, Alexander S Severinov, Konstantin Dubiley, Svetlana Mechanism of translation inhibition by type II GNAT toxin AtaT2 |
title | Mechanism of translation inhibition by type II GNAT toxin AtaT2 |
title_full | Mechanism of translation inhibition by type II GNAT toxin AtaT2 |
title_fullStr | Mechanism of translation inhibition by type II GNAT toxin AtaT2 |
title_full_unstemmed | Mechanism of translation inhibition by type II GNAT toxin AtaT2 |
title_short | Mechanism of translation inhibition by type II GNAT toxin AtaT2 |
title_sort | mechanism of translation inhibition by type ii gnat toxin atat2 |
topic | RNA and RNA-protein complexes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470980/ https://www.ncbi.nlm.nih.gov/pubmed/32597957 http://dx.doi.org/10.1093/nar/gkaa551 |
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