Jurėnas, D, Chatterjee, S, Konijnenberg, A et al. (4 more authors) (2017) AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet. Nature Chemical Biology, 13 (6). pp. 640-646. ISSN 1552-4450
Abstract
Toxin–antitoxin (TA) loci are prevalent in bacterial genomes. They are suggested to play a central role in dormancy and persister states. Under normal growth conditions, TA toxins are neutralized by their cognate antitoxins, and under stress conditions, toxins are freed and inhibit essential cellular processes using a variety of mechanisms. Here we characterize ataR–ataT, a novel TA system, from enterohemorrhagic Escherichia coli. We show that the toxin AtaT is a GNAT family enzyme that transfers an acetyl group from acetyl coenzyme A to the amine group of the methionyl aminoacyl moiety of initiator tRNA. AtaT specifically modifies Met-tRNAfMet, but no other aminoacyl-tRNAs, including the elongator Met-tRNAMet. We demonstrate that once acetylated, AcMet-tRNAfMet fails to interact with initiation factor-2 (IF2), resulting in disruption of the translation initiation complex. This work reveals a new mechanism of translation inhibition and confirms Met-tRNAfMet as a prime target to efficiently block cell growth.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2017 Nature America, Inc., part of Springer Nature. This is an author produced version of a paper published in Nature Chemical Biology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Bacteria; RNA; Translation |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Jul 2017 09:41 |
Last Modified: | 03 Oct 2017 05:39 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/nchembio.2346 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:118591 |