7AWK

Crystal structure of the HigB1 toxin mutant K95A from Mycobacterium tuberculosis (Rv1955)

Summary for 7AWK

• Entry DOI: 10.2210/pdb7awk/pdb
• Descriptor: Probable endoribonuclease HigB1 (2 entities in total)
• Functional Keywords: mycobacterium tuberculosis, toxin-antitoxin-chaperone, rnase, toxin
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 1
• Total formula weight: 14920.28

Authors

Bigot, D.J.,Guillet, V.,Mourey, L. (deposition date: 2020-11-08, release date: 2021-11-24, Last modification date: 2024-06-19)

Primary citation

Mansour, M.,Giudice, E.,Xu, X.,Akarsu, H.,Bordes, P.,Guillet, V.,Bigot, D.J.,Slama, N.,D'urso, G.,Chat, S.,Redder, P.,Falquet, L.,Mourey, L.,Gillet, R.,Genevaux, P.
Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis.
Nat Commun, 13:2641-2641, 2022

PubMed 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.

PubMed: 35552387
DOI: 10.1038/s41467-022-30373-w

Experimental method

X-RAY DIFFRACTION (1.91 Å)