Issue 33, 2021

DsbA is a redox-switchable mechanical chaperone


DsbA is a ubiquitous bacterial oxidoreductase that associates with substrates during and after translocation, yet its involvement in protein folding and translocation remains an open question. Here we demonstrate a redox-controlled chaperone activity of DsbA, on both cysteine-containing and cysteine-free substrates, using magnetic tweezers-based single molecule force spectroscopy that enables independent measurements of oxidoreductase activity and chaperone behavior. Interestingly we found that this chaperone activity is tuned by the oxidation state of DsbA; oxidized DsbA is a strong promoter of folding, but the effect is weakened by the reduction of the catalytic CXXC motif. We further localize the chaperone binding site of DsbA using a seven-residue peptide which effectively blocks the chaperone activity. We found that the DsbA assisted folding of proteins in the periplasm generates enough mechanical work to decrease the ATP consumption needed for periplasmic translocation by up to 33%.

Graphical abstract: DsbA is a redox-switchable mechanical chaperone

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Article information

Article type
Edge Article
06 Jun 2021
17 Jul 2021
First published
19 Jul 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 11109-11120

DsbA is a redox-switchable mechanical chaperone

E. C. Eckels, D. Chaudhuri, S. Chakraborty, D. J. Echelman and S. Haldar, Chem. Sci., 2021, 12, 11109 DOI: 10.1039/D1SC03048E

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