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TitleSubstrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 2641, Year 2022
Publish dateMay 12, 2022
AuthorsMoise Mansour / Emmanuel Giudice / Xibing Xu / Hatice Akarsu / Patricia Bordes / Valérie Guillet / Donna-Joe Bigot / Nawel Slama / Gaetano D'urso / Sophie Chat / Peter Redder / Laurent Falquet / Lionel Mourey / Reynald Gillet / Pierre Genevaux /
PubMed AbstractToxins 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 ...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.
External linksNat Commun / PubMed:35552387 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.91 - 3.11 Å
Structure data

12261

7nbu

EMDB-12261, PDB-7nbu:
Structure of the HigB1 toxin mutant K95A from Mycobacterium tuberculosis (Rv1955) and its target, the cspA mRNA, on the E. coli Ribosome.
Method: EM (single particle) / Resolution: 3.11 Å

PDB-7awk:
Crystal structure of the HigB1 toxin mutant K95A from Mycobacterium tuberculosis (Rv1955)
Method: X-RAY DIFFRACTION / Resolution: 1.91 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-MG:
Unknown entry

ChemComp-FME:
N-FORMYLMETHIONINE

ChemComp-ZN:
Unknown entry

Source
  • escherichia coli k-12 (bacteria)
  • Mycobacterium tuberculosis (bacteria)
  • escherichia coli (E. coli)
  • mycobacterium tuberculosis h37rv (bacteria)
  • mycobacterium tuberculosis (strain atcc 25618 / h37rv) (bacteria)
KeywordsTOXIN / Mycobacterium tuberculosis / Toxin-Antitoxin-Chaperone / RNase

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