A pre-existing hydrophobic collapse in the unfolded state of an ultrafast folding protein
| Autor: | Jasper C. Lin, P. J. Hore, Niels H. Andersen, Martin Goez, K. Hun Mok, Lars T. Kuhn, Iain J. Day |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Protein Denaturation Protein Folding Magnetic Resonance Spectroscopy Time Factors Multidisciplinary Photochemistry Protein Conformation Chemistry Energy landscape Protein Engineering Contact order Article Folding (chemistry) Crystallography Protein structure Models Chemical Biophysics Native state Protein folding Folding funnel Hydrophobic collapse Hydrophobic and Hydrophilic Interactions |
| DOI: | 10.1038/nature05728 |
| Popis: | 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 simulations1,2. Even though some unfolded and partially folded proteins are now known to possess biological function3 or to be involved in aggregation phenomena associated with disease states1,4, 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 (ref. 5), we report photochemically induced dynamic nuclear polarization NMR6 pulse-labelling experiments that involve rapid in situ protein refolding7,8. 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 hydrophobic collapse in the unfolded state of this small protein, with strong inter-residue contacts between side chains that are relatively distant from one another in the native state. Prior structuring, even with the formation of non-native rather than native contacts, may be a feature associated with fast folding events in proteins. |
| Databáze: | OpenAIRE |
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