Substrate Recognition and Cryo-EM Structure of the Ribosome-bound TAC Toxin of Mycobacterium Tuberculosis

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 13

PMID 35552387

Authors

Moise Mansour

Emmanuel Giudice

Xibing Xu

Hatice Akarsu

Patricia Bordes

Valerie Guillet

Donna-Joe Bigot

Nawel Slama

Gaetano DUrso

Sophie Chat

Peter Redder

Laurent Falquet

Lionel Mourey

Reynald Gillet

Pierre Genevaux

Affiliations

Soon will be listed here.

Abstract

Toxins of toxin-antitoxin systems use diverse mechanisms to control bacterial growth. Here, we focus on the deleterious toxin of the atypical tripartite toxin-antitoxin-chaperone (TAC) system of Mycobacterium tuberculosis, whose inhibition requires the concerted action of the antitoxin and its dedicated SecB-like chaperone. We show that the TAC toxin is a bona fide ribonuclease and identify exact cleavage sites in mRNA targets on a transcriptome-wide scale in vivo. mRNA cleavage by the toxin occurs after the second nucleotide of the ribosomal A-site codon during translation, with a strong preference for CCA codons in vivo. Finally, we report the cryo-EM structure of the ribosome-bound TAC toxin in the presence of native M. tuberculosis cspA mRNA, revealing the specific mechanism by which the TAC toxin interacts with the ribosome and the tRNA in the P-site to cleave its mRNA target.

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