Probing the protein-folding mechanism using denaturant and temperature effects on rate constants
Abstract
Analysis of effects of denaturants and temperature on folding and unfolding rate constants of 13 globular proteins yields the amount and composition of the surface buried in folding to and from the high-free-energy transition state (TS), and thereby provides information about folding mechanisms and early unstable folding intermediates. All 13 proteins preferentially bury amide surface in folding to TS; amounts of amide and hydrocarbon surface buried in folding to TS generally exceed those buried in forming the native secondary structure. From this, we conclude that most native secondary structure forms in early unstable folding intermediates and that conversion of these intermediates to TS involves nucleation of tertiary interactions, allowing preferential burial of hydrocarbon surface as TS folds.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- October 2013
- DOI:
- 10.1073/pnas.1311948110
- Bibcode:
- 2013PNAS..11016784G