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A pre-existing hydrophobic collapse in the unfolded state of an ultrafast folding protein
journal contribution
posted on 2023-06-08, 09:00 authored by K Hun Mok, Lars T Kuhn, Martin Goez, Iain Day, Jasper C Lin, Niels H Andersen, P J HoreInsights into the conformational passage of a polypeptide chain across its free energy landscape have come from the judicious combination of experimental studies and computer simulations. Even though some unfolded and partially folded proteins are now known to possess biological function or to be involved in aggrega- tion phenomena associated with disease states, experimentally derived atomic-level information on these structures remains sparse as a result of conformational heterogeneity and dynamics. Here we present a technique that can provide such information. Using a Trp-cage miniprotein known as TC5b, we report photochemically induced dynamic nuclear polarization NMR6 pulse-labelling experiments that involve rapid in situ protein refolding. These experiments allow dipolar cross-relaxation with hyperpolarized aromatic side chain nuclei in the unfolded state to be identified and quantified in the resulting folded-state spectrum. We find that there is residual structure due to hydro- phobic collapse in the unfolded state of this small protein, with strong inter-residue contacts between side chains that are rela- tively distant from one another in the native state. Prior structur- ing, even with the formation of non-native rather than native contacts, may be a feature associated with fast folding events in proteins.
History
Publication status
- Published
Journal
NatureISSN
0028-0836Publisher
Nature Publishing GroupExternal DOI
Issue
714Volume
447Page range
106-109Pages
4.0Department affiliated with
- Chemistry Publications
Notes
ID contributed to the development of the injection device, performed the NMR diffusion measurements, data analysis, interpretation and co authored the paper. First demonstration of the combination of photo-CIDNP, NMR-based rapid mixing and NOE generation to provide detailed, residue specific structural information on the unfolded state of a protein.Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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