The ribosome lowers the entropic penalty of protein folding.

Autor: Streit JO; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Bukvin IV; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Chan SHS; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK. s.chan.12@ucl.ac.uk., Bashir S; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Woodburn LF; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Włodarski T; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Figueiredo AM; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Jurkeviciute G; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Sidhu HK; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Hornby CR; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Waudby CA; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Cabrita LD; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK., Cassaignau AME; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK. anais.cassaignau.09@alumni.ucl.ac.uk., Christodoulou J; Institute of Structural and Molecular Biology, Department of Structural and Molecular Biology, University College London, London, UK. j.christodoulou@ucl.ac.uk.; Department of Biological Sciences, Birkbeck College, London, UK. j.christodoulou@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Sep; Vol. 633 (8028), pp. 232-239. Date of Electronic Publication: 2024 Aug 07.
DOI: 10.1038/s41586-024-07784-4
Abstrakt: Most proteins fold during biosynthesis on the ribosome 1 , 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 19 F NMR experiments confirm that this destabilization reduces the entropic penalty of folding by up to 30 kcal mol -1 and promotes formation of partially folded intermediates on the ribosome, an observation that extends to other protein domains and is obligate for some proteins to acquire their active conformation. The thermodynamic effects also contribute to the ribosome protecting the nascent chain from mutation-induced unfolding, which suggests a crucial role of the ribosome in supporting protein evolution. By correlating nascent chain structure and dynamics to their folding energetics and post-translational outcomes, our findings establish the physical basis of the distinct thermodynamics of co-translational protein folding.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: