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 PubMedSecB chaperones assist protein export by binding both unfolded proteins and the SecA motor. Certain SecB homologs can also control toxin-antitoxin (TA) systems known to modulate bacterial growth in response to stress. In such TA-chaperone (TAC) systems, SecB assists the folding and prevents degradation of the antitoxin, thus facilitating toxin inhibition. Chaperone dependency is conferred by a C-terminal extension in the antitoxin known as chaperone addiction (ChAD) sequence, which makes the antitoxin aggregation-prone and prevents toxin inhibition. Using TAC of Mycobacterium tuberculosis, we present the structure of a SecB-like chaperone bound to its ChAD peptide. We find differences in the binding interfaces when compared to SecB-SecA or SecB-preprotein complexes, and show that the antitoxin can reach a functional form while bound to the chaperone. This work reveals how chaperones can use discrete surface binding regions to accommodate different clients or partners and thereby expand their substrate repertoire and functions. Structural insights into chaperone addiction of toxin-antitoxin systems.,Guillet V, Bordes P, Bon C, Marcoux J, Gervais V, Sala AJ, Dos Reis S, Slama N, Mares-Mejia I, Cirinesi AM, Maveyraud L, Genevaux P, Mourey L Nat Commun. 2019 Feb 15;10(1):782. doi: 10.1038/s41467-019-08747-4. PMID:30770830[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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