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Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis

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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https://hal-cnrs.archives-ouvertes.fr/hal-03751990
Contributor : Lionel Mourey Connect in order to contact the contributor
Submitted on : Tuesday, August 16, 2022 - 10:33:22 AM
Last modification on : Thursday, September 29, 2022 - 4:54:02 AM

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Moise Mansour, Emmanuel Giudice, Xibing Xu, Hatice Akarsu, Patricia Bordes, et al.. Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis. Nature Communications, Nature Publishing Group, 2022, 13, pp.2641. ⟨10.1038/s41467-022-30373-w⟩. ⟨hal-03751990⟩

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