The ribosome lowers the entropic penalty of protein folding.

ABSTRACT: Most proteins fold during biosynthesis on the ribosome¹, and co-translational folding energetics, pathways and outcomes of many proteins have been found to differ considerably from those in refolding studies^2-10. The origin of this folding modulation by the ribosome has remained unknown. Here we have determined atomistic structures of the unfolded state of a model protein on and off the ribosome, which reveal that the ribosome structurally expands the unfolded nascent chain and increases its solvation, resulting in its entropic destabilization relative to the peptide chain in isolation. Quantitative ¹⁹F NMR experiments confirm that this destabilization reduces the entropic penalty of folding by up to 30 kcal mol^-1 and promotes formation of partia

SUBMITTER: Streit JO 

PROVIDER: S-EPMC11374706 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature