5mtw
From Proteopedia
Mycobacterium tuberculosis Rv1957 SecB-like chaperone in complex with a ChAD peptide from Rv1956 HigA1 antitoxin
Structural highlights
Function[SECBL_MYCTU] Chaperone component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Prevents antitoxin HigA1 aggregation in vitro at a 1:3 chaperone:antitoxin ratio, probably also protects antitoxin HigA1 from protease. Required for neutralization of toxin HigB1 upon ectopic expression in Mycobacterium marinum or E.coli. When expressed in E.coli complements a secB deletion, restores export of OmpA and MBP and inhibits aggregation of proOmpC although it is less efficient than endogenous SecB. Complements the general chaperone function of E.coli SecB less well.[1] [HIGA1_MYCTU] Antitoxin component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Upon expression in M.smegmatis neutralizes the effect of cognate toxin HigB1. 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. Antitoxin aggregation and degradation are prevented by the chaperone.[2] In M.tuberculosis represses expression of the Rv1954A-higB1-higA1-Rv1957 operon promoter but not that of the higB1-higA1-Rv1957 operon.[3] Publication Abstract from PubMedBacterial toxin-antitoxin (TA) systems, in which a labile antitoxin binds and inhibits the toxin, can promote adaptation and persistence by modulating bacterial growth in response to stress. Some atypical TA systems, known as tripartite toxin-antitoxin-chaperone (TAC) modules, include a molecular chaperone that facilitates folding and protects the antitoxin from degradation. Here we use a TAC module from Mycobacterium tuberculosis as a model to investigate the molecular mechanisms by which classical TAs can become 'chaperone-addicted'. The chaperone specifically binds the antitoxin at a short carboxy-terminal sequence (chaperone addiction sequence, ChAD) that is not present in chaperone-independent antitoxins. In the absence of chaperone, the ChAD sequence destabilizes the antitoxin, thus preventing toxin inhibition. Chaperone-ChAD pairs can be transferred to classical TA systems or to unrelated proteins and render them chaperone-dependent. This mechanism might be used to optimize the expression and folding of heterologous proteins in bacterial hosts for biotechnological or medical purposes. Chaperone addiction of toxin-antitoxin systems.,Bordes P, Sala AJ, Ayala S, Texier P, Slama N, Cirinesi AM, Guillet V, Mourey L, Genevaux P Nat Commun. 2016 Nov 9;7:13339. doi: 10.1038/ncomms13339. PMID:27827369[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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