RT Journal Article
SR Electronic
T1 Twin-arginine translocase component TatB performs folding quality control via a general chaperone activity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.11.089458
DO 10.1101/2020.05.11.089458
A1 May N. Taw
A1 Jason T. Boock
A1 Daniel Kim
A1 Mark A. Rocco
A1 Dujduan Waraho-Zhmayev
A1 Matthew P. DeLisa
YR 2020
UL http://biorxiv.org/content/early/2020/05/12/2020.05.11.089458.abstract
AB The twin-arginine translocation (Tat) pathway involves an inbuilt quality control (QC) system that synchronizes proofreading of substrate protein folding with lipid bilayer transport. However, the molecular details of this QC mechanism remain poorly understood. Here, we hypothesized that the conformational state of Tat substrates is directly sensed by the TatB component of the bacterial Tat translocase. In support of this hypothesis, several TatB variants in which the cytoplasmic membrane-extrinsic domain was either truncated or mutated in the vicinity of a conserved, highly flexible α-helical domain were observed to form functional translocases in vivo that had compromised QC activity as evidenced by the uncharacteristic export of several misfolded protein substrates. In vitro folding experiments revealed that the membrane-extrinsic domain of TatB possessed general chaperone activity, transiently binding to highly structured, partially unfolded intermediates of a model protein, citrate synthase, thereby preventing its irreversible aggregation and stabilizing the active species. Collectively, these results suggest that the Tat translocase may use chaperone-like client recognition to monitor the conformational status of its substrates.Competing Interest StatementThe authors have declared no competing interest.