An experimental survey of the transition between two-state and downhill protein folding scenarios
- 19 February 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (7) , 2369-2374
- https://doi.org/10.1073/pnas.0711908105
Abstract
A kinetic and thermodynamic survey of 35 WW domain sequences is used in combination with a model to discern the energetic requirements for the transition from two-state folding to downhill folding. The sequences used exhibit a 600-fold range of folding rates at the temperature of maximum folding rate. Very stable proteins can achieve complete downhill folding when the temperature is lowered sufficiently below the melting temperature, and then at even lower temperatures they become two-state folders again because of cold denaturation. Less stable proteins never achieve a sufficient bias to fold downhill because of the onset of cold denaturation. The model, considering both heat and cold denaturation, reveals that to achieve incipient downhill folding (barrier /=50 degrees C for incipient downhill folding and >/=90 degrees C for downhill folding.Keywords
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