Mechanism of chaperone coordination during cotranslational protein folding in bacteria.

Abstract

Protein folding is assisted by molecular chaperones that bind nascent polypeptides during mRNA translation. Several structurally distinct classes of chaperones promote de novo folding, suggesting that their activities are coordinated at the ribosome. We used biochemical reconstitution and structural proteomics to explore the molecular basis for cotranslational chaperone action in bacteria. We found that chaperone binding is disfavored close to the ribosome, allowing folding to precede chaperone recruitment. Trigger factor recognizes compact folding intermediates that expose an extensive unfolded surface, and dictates DnaJ access to nascent chains. DnaJ uses a large surface to bind structurally diverse intermediates and recruits DnaK to sequence-diverse solvent-accessible sites. Neither Trigger factor, DnaJ, nor DnaK destabilize cotranslational folding intermediates. Instead, the chaperones collaborate to protect incipient structure in the nascent polypeptide well beyond the ribosome exit tunnel. Our findings show how the chaperone network selects and modulates cotranslational folding intermediates.

Publication DOI: https://doi.org/10.1016/j.molcel.2024.06.002
Divisions: Aston University (General)
Additional Information: Copyright © 2024 The Authors. Published by Elsevier Inc. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. You are not required to obtain permission to reuse this article.
Publication ISSN: 1097-4164
Last Modified: 31 Mar 2025 07:27
Date Deposited: 24 Jan 2025 14:35
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Related URLs: https://www.cel ... Fshowall%3Dtrue (Publisher URL)
PURE Output Type: Article
Published Date: 2024-07-11
Published Online Date: 2024-07-11
Accepted Date: 2024-06-21
Authors: Roeselova, Alzbeta
Maslen, Sarah L
Shivakumaraswamy, Santosh
Pellowe, Grant (ORCID Profile 0000-0003-4314-5261)
Howell, Steven
Joshi, Dhira
Redmond, Joanna
Kjaer, Svend
Skehel, J Mark
Balchin, David

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