2024-03-29T01:22:56Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/94112021-12-27T16:46:39Zcom_10261_86com_10261_1col_10261_339
DIGITAL.CSIC
author
Naganathan, Athi N.
author
Doshi, Urmi
author
Muñoz, Víctor
2008-12-31T09:33:29Z
2008-12-31T09:33:29Z
2007-04-10
J. Am. Chem. Soc. 129(17): 5673-5682 (2007)
0002-7863
http://hdl.handle.net/10261/9411
10.1021/ja0689740
17419630
Recent experimental work on fast protein folding brings about an intriguing paradox. Microsecond-folding proteins are supposed to fold near or at the folding speed limit (downhill folding), but yet their folding behavior seems to comply with classical two-state analyses, which imply the crossing of high free energy barriers. However, close inspection of chemical and thermal denaturation kinetic experiments in fast-folding proteins reveals systematic deviations from two-state behavior. Using a simple one-dimensional free energy surface approach we find that such deviations are indeed diagnostic of marginal folding barriers. Furthermore, the quantitative analysis of available fast-kinetic data indicates that many microsecond-folding proteins fold downhill in native conditions. All of these proteins are then promising candidates for an atom-by-atom analysis of protein folding using nuclear magnetic resonance. We also find that the diffusion coefficient for protein folding is strongly temperature dependent, corresponding to an activation energy of ~1 kJ·mol-1 per protein residue. As a consequence, the folding speed limit at room temperature is about an order of magnitude slower than the ~ 1 μs estimates from high-temperature T-jump experiments. Our analysis is quantitatively consistent with the available thermodynamic and kinetic data on slow two-state folding proteins and provides a straightforward explanation for the apparent fast-folding paradox.
eng
closedAccess
Protein folding
Folding kinetics
Downhill folding
Free energy barriers
Two-state analyses
Diffusion coefficient
Protein folding kinetics: barrier effects in chemical and thermal denaturation experiments
artículo
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