A pre-existing hydrophobic collapse in the unfolded state of an ultrafast folding protein

Mok, K Hun, Kuhn, Lars T, Goez, Martin, Day, Iain J, Lin, Jasper C, Andersen, Niels H and Hore, P J (2007) A pre-existing hydrophobic collapse in the unfolded state of an ultrafast folding protein. Nature, 447 (714). pp. 106-109. ISSN 0028-0836

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Insights 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.

Item Type: Article
Additional Information: 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.
Schools and Departments: School of Life Sciences > Chemistry
Depositing User: Iain Day
Date Deposited: 06 Feb 2012 21:09
Last Modified: 29 Mar 2012 08:55
URI: http://sro.sussex.ac.uk/id/eprint/29826
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