title: AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet.
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-tRNAfMetfails 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-tRNAfMetas a prime target to efficiently block cell growth.
authors.affiliation: Laboratoire de Génétique et Physiologie Bactérienne, Université Libre de Bruxelles, Gosselies, Belgium.|Department of Biochemistry and Molecular Biology, Vilnius University Joint Life Sciences Center, Vilnius, Lithuania.
authors.forename: Dukas
authors.initials: D
authors.lastname: Jurėnas
authors.affiliation: Biomolecular and Analytical Mass Spectrometry Group, Department of Chemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Sneha
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Biomolecular and Analytical Mass Spectrometry Group, Department of Chemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Albert
authors.initials: A
authors.lastname: Konijnenberg
authors.affiliation: Biomolecular and Analytical Mass Spectrometry Group, Department of Chemistry, University of Antwerp, Antwerp, Belgium.|Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.|School of Molecular and Cellular Biology, University of Leeds, Leeds, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
authors.affiliation: Laboratoire de Microbiologie, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Louis
authors.initials: L
authors.lastname: Droogmans
authors.affiliation: Laboratoire de Biologie Structurale et Biophysique, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Abel
authors.initials: A
authors.lastname: Garcia-Pino
authors.affiliation: Laboratoire de Génétique et Physiologie Bactérienne, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Laurence
authors.identifier: 0000-0002-7778-1736
authors.initials: L
authors.lastname: Van Melderen
mesh_terms: D000107:Acetylation; D051046:Amino-Acid N-Acetyltransferase / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004926:Escherichia coli; D005786:Gene Expression Regulation / Q000235:genetics*; D008954:Models, Biological; D014176:Protein Biosynthesis; D012358:RNA, Transfer, Met / Q000378:metabolism*
chemical_list: D012358:RNA, Transfer, Met; D051046:Amino-Acid N-Acetyltransferase