Mechanism of chaperone coordination during cotranslational protein folding in bacteria.
Mol Cell
; 84(13): 2455-2471.e8, 2024 Jul 11.
Article
in En
| MEDLINE
| ID: mdl-38908370
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Ribosomes
/
Protein Biosynthesis
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Protein Folding
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HSP70 Heat-Shock Proteins
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Escherichia coli Proteins
/
Escherichia coli
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HSP40 Heat-Shock Proteins
Language:
En
Year:
2024
Type:
Article