Structures of protein folding intermediates on the ribosome - PubMed
4 hours ago
- #Ribosome NMR structure
- #Protein folding intermediates
- #Cotranslational folding
- The ribosome influences nascent polypeptide chains toward biologically active states during cotranslational folding (coTF).
- Cotranslational folding often involves stable intermediates that persist longer than in vitro refolding and are absent or transient off the ribosome.
- Structures of two folding intermediates of an immunoglobulin-like domain on the ribosome were determined using 19F NMR, paramagnetic relaxation enhancement, protein engineering, and molecular dynamics simulations.
- The intermediate structures feature native-like folded cores with nonnative termini, enabling distinct chaperone binding and suggesting parallel folding pathways.
- These intermediate structures are conserved within the protein domain family, unlike their in vitro refolding mechanisms.
- The structural ensembles reveal diverse conformations during coTF, allowing the ribosome to passively promote efficient folding and maintain proteostasis.