Mechanism of chaperone coordination during cotranslational protein folding in bacteria
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Alzbeta Roeselova Sarah L Maslen Santosh Shivakumaraswamy Grant Pellowe Steven Howell Dhira Joshi Joanna Redmond Svend Kjaer Mark Skehel David BalchinAbstract
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.
Journal details
Journal
Molecular Cell
Volume
84
Issue number
13
Pages
2455-2471.e8
Available online
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Publisher website (DOI)
10.1016/j.molcel.2024.06.002
Europe PubMed Central
38908370
Pubmed
38908370
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