The membrane-binding bacterial toxin long direct repeat D inhibits protein translation.

Autor: Pulido S; Institute of Chemistry, University of Graz, Graz, Austria; LifeFactors ZF S.A.S., Zona France Rionegro, Rionegro, Colombia., Rückert H; Institute of Chemistry, University of Graz, Graz, Austria., Falsone SF; Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria., Göbl C; Dept. of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand., Meyer NH; Institute of Chemistry, University of Graz, Graz, Austria; Division of General and Visceral Surgery, Department of Human Medicine, University of Oldenburg, Germany. Electronic address: helge.meyer@uni-oldenburg.de., Zangger K; Institute of Chemistry, University of Graz, Graz, Austria. Electronic address: klaus.zangger@uni-graz.at.
Jazyk: angličtina
Zdroj: Biophysical chemistry [Biophys Chem] 2023 Jul; Vol. 298, pp. 107040. Date of Electronic Publication: 2023 May 09.
DOI: 10.1016/j.bpc.2023.107040
Abstrakt: Bacterial plasmids and chromosomes widely contain toxin-antitoxin (TA) loci, which are implicated in stress response, growth regulation and even tolerance to antibiotics and environmental stress. Type I TA systems consist of a stable toxin-expressing mRNA, which is counteracted by an unstable RNA antitoxin. The Long Direct Repeat (LDR-) D locus, a type I TA system of Escherichia Coli (E. coli) K12, encodes a 35 amino acid toxic peptide, LdrD. Despite being characterized as a bacterial toxin, causing rapid killing and nucleoid condensation, little was known about its function and its mechanism of toxicity. Here, we show that LdrD specifically interacts with ribosomes which potentially blocks translation. Indeed, in vitro translation of LdrD-coding mRNA greatly reduces translation efficiency. The structure of LdrD in a hydrophobic environment, similar to the one found in the interior of ribosomes was determined by NMR spectroscopy in 100% trifluoroethanol solution. A single compact α-helix was found which would fit nicely into the ribosomal exit tunnel. Therefore, we conclude that rather than destroying bacterial membranes, LdrD exerts its toxic activity by inhibiting protein synthesis through binding to the ribosomes.
Competing Interests: Declaration of Competing Interest We confirm that we have no conflicts of interest to disclose.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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