Ivana V. Bukvin

All Publications

• The ribosome lowers the entropic penalty of protein folding. Nature Streit, J. O., Bukvin, I. V., Chan, S. H., Bashir, S., Woodburn, L. F., Wlodarski, T., Figueiredo, A. M., Jurkeviciute, G., Sidhu, H. K., Hornby, C. R., Waudby, C. A., Cabrita, L. D., Cassaignau, A. M., Christodoulou, J. 2024

  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 studies2-10. 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 30kcalmol-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.

  View details for DOI 10.1038/s41586-024-07784-4

  View details for PubMedID 39112704

• Interactions between nascent proteins and the ribosome surface inhibit co-translational folding NATURE CHEMISTRY Cassaignau, A. E., Wlodarski, T., Chan, S. S., Woodburn, L. F., Bukvin, I. V., Streit, J. O., Cabrita, L. D., Waudby, C. A., Christodoulou, J. 2021; 13 (12): 1214-+

  Abstract

  Most proteins begin to fold during biosynthesis on the ribosome. It has been suggested that interactions between the emerging polypeptide and the ribosome surface might allow the ribosome itself to modulate co-translational folding. Here we combine protein engineering and NMR spectroscopy to characterize a series of interactions between the ribosome surface and unfolded nascent chains of the immunoglobulin-like FLN5 filamin domain. The strongest interactions are found for a C-terminal segment that is essential for folding, and we demonstrate quantitative agreement between the strength of this interaction and the energetics of the co-translational folding process itself. Mutations in this region that reduce the extent of binding result in a shift in the co-translational folding equilibrium towards the native state. Our results therefore demonstrate that a competition between folding and binding provides a simple, dynamic mechanism for the modulation of co-translational folding by the ribosome.

  View details for DOI 10.1038/s41557-021-00796-x

  View details for Web of Science ID 000707290700003

  View details for PubMedID 34650236

  View details for PubMedCentralID PMC8627912