Document Type

Article

Version Deposited

Published Version

Publication Date

9-6-2018

Publication Title

Nucleic acids research

DOI

10.1093/nar/gky560

Abstract

Prokaryotic toxin-antitoxin (TA) modules are highly abundant and are involved in stress response and drug tolerance. The most common type II TA modules consist of two interacting proteins. The type II toxins are diverse enzymes targeting various essential intracellular targets. The antitoxin binds to cognate toxin and inhibits its function. Recently, TA modules whose toxins are GNAT-family acetyltransferases were described. For two such systems, the target of acetylation was shown to be aminoacyl-tRNA: the TacT toxin targets aminoacylated elongator tRNAs, while AtaT targets the amino acid moiety of initiating tRNAMet. We show that the itaRT gene pair from Escherichia coli encodes a TA module with acetyltransferase toxin ItaT that specifically and exclusively acetylates Ile-tRNAIle thereby blocking translation and inhibiting cell growth. ItaT forms a tight complex with the ItaR antitoxin, which represses the transcription of itaRT operon. A comprehensive bioinformatics survey of GNAT acetyltransferases reveals that enzymes encoded by validated or putative TA modules are common and form a distinct branch of the GNAT family tree. We speculate that further functional analysis of such TA modules will result in identification of enzymes capable of specifically targeting many, perhaps all, aminoacyl tRNAs.

Comments

This article is available under the Creative Commons CC-BY-NC license and permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Published Citation

Wilcox B, Osterman I, Serebryakova M, Lukyanov D, Komarova E, Gollan B, Morozova N, Wolf YI, Makarova KS, Helaine S, Sergiev P, Dubiley S, Borukhov S, Severinov K. Escherichia coli ItaT is a Type II toxin that inhibits translation by acetylating isoleucyl-tRNAIle. Nucleic Acids Research. 2018 Sep 6;46(15):7873-7885. doi: 10.1093/nar/gky560. PMID: 29931259. PMCID: PMC6125619.

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