7awk
Crystal structure of the HigB1 toxin mutant K95A from Mycobacterium tuberculosis (Rv1955)
Structural highlights
Function[HIGB1_MYCTU] Toxic component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Upon expression in M.smegmatis inhibits colony formation and cell growth (PubMed:20011113, PubMed:23927792). Ectopic expression in wild-type M.tuberculosis has no effect on cell growth; ectopic expression in a triple higB1-higA1-Rv1957 (delta TAC) disruption mutant causes growth arrest, killing a considerable proportion of the cells. Increased ectopic expression leads to decreased levels of IdeR- and Zur-regulated genes as well as cleavage within the mRNA region of tmRNA (transfer-mRNA), strongly suggesting it is an endoribonuclease; also degrades E.coli and M-smegmatis tmRNA (PubMed:23927792). Its toxic effect is neutralized by coexpression with antitoxin HigA. Neutralization of HigB1 toxin in E.coli or M.marinum also requires SecB-like chaperone Rv1957, making this the first toxin-antitoxin chaperone (TAC) system (PubMed:21536872).[1] [2] [3] [4] Publication Abstract from PubMedToxins 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. Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis.,Mansour M, Giudice E, Xu X, Akarsu H, Bordes P, Guillet V, Bigot DJ, Slama N, D'urso G, Chat S, Redder P, Falquet L, Mourey L, Gillet R, Genevaux P Nat Commun. 2022 May 12;13(1):2641. doi: 10.1038/s41467-022-30373-w. PMID:35552387[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
