Protein Folding in Classical Perspective: Folding of Horse Cytochrome c Export

@article{citeulike:3343527, abstract = {Abstract: Proteins meet with the stipulations of Levinthal. Two test tube variants of ferrocytochrome c (ferrocyt c) whose thermodynamic stabilities are vastly different refold to the same global minimum under a given final native condition, and they do so quickly at rates that do not reflect a strong dependence on the thermodynamic driving force. The transition-state ensemble is more unfolded-like, and the folding barrier offered is energetically sizable. The experiments involve neutral- (pH 7) and alkaline ferrocyt c pH (12.7), whose aqueous stabilities are 18 (±0.3) and 3 (±0.5) kcal mol-1, respectively. But the large disparity in thermodynamic stability is not strongly reflected in their refolding rates. Cross-pH studies, where GdnHCl-unfolded states of neutral- and alkaline ferrocyt c are allowed to refold to the same final pH and denaturant concentration, indicate that the refolding rates are largely independent of the stability, configuration, ionization, and solvation of the initial unfolded state. Also, burst relaxation signals in cross-pH refolding runs show the same quantitative dependence on GdnHCl, suggesting that the earliest relaxation or reconfiguration of the chains must be the same and is independent of the initial equilibrium unfolded state. Analyses along the classical line indicate an early transition state where much less than a third of the protein surface that is buried in the native state becomes buried. The barrier energy is of the order of 10 kBT. The results, apparently inconsistent with the predictions of the funnel model, afford a mechanistic description of folding in which the folding time of small single-domain proteins is set by the time needed for the denatured polypeptide to search-find a nativelike topology.}, address = {School of Chemistry, University of Hyderabad, Hyderabad 500046, India}, author = {Bhuyan, A. K. and Rao, D. K. and Prabhu, N. P.}, citeulike-article-id = {3343527}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/bi047897n}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/bi047897n}, day = {1}, doi = {10.1021/bi047897n}, journal = {Biochemistry}, keywords = {folding, kinetics}, month = {March}, number = {8}, pages = {3034--3040}, posted-at = {2008-09-27 02:42:06}, priority = {2}, title = {Protein Folding in Classical Perspective: Folding of Horse Cytochrome c}, url = {http://dx.doi.org/10.1021/bi047897n}, volume = {44}, year = {2005} }

TY - JOUR ID - citeulike:3343527 L3 - citeulike-article-id:3343527 N2 - Abstract: Proteins meet with the stipulations of Levinthal. Two test tube variants of ferrocytochrome c (ferrocyt c) whose thermodynamic stabilities are vastly different refold to the same global minimum under a given final native condition, and they do so quickly at rates that do not reflect a strong dependence on the thermodynamic driving force. The transition-state ensemble is more unfolded-like, and the folding barrier offered is energetically sizable. The experiments involve neutral- (pH 7) and alkaline ferrocyt c pH (12.7), whose aqueous stabilities are 18 (±0.3) and 3 (±0.5) kcal mol-1, respectively. But the large disparity in thermodynamic stability is not strongly reflected in their refolding rates. Cross-pH studies, where GdnHCl-unfolded states of neutral- and alkaline ferrocyt c are allowed to refold to the same final pH and denaturant concentration, indicate that the refolding rates are largely independent of the stability, configuration, ionization, and solvation of the initial unfolded state. Also, burst relaxation signals in cross-pH refolding runs show the same quantitative dependence on GdnHCl, suggesting that the earliest relaxation or reconfiguration of the chains must be the same and is independent of the initial equilibrium unfolded state. Analyses along the classical line indicate an early transition state where much less than a third of the protein surface that is buried in the native state becomes buried. The barrier energy is of the order of 10 kBT. The results, apparently inconsistent with the predictions of the funnel model, afford a mechanistic description of folding in which the folding time of small single-domain proteins is set by the time needed for the denatured polypeptide to search-find a nativelike topology. IS - 8 JF - Biochemistry AD - School of Chemistry, University of Hyderabad, Hyderabad 500046, India EP - 3040 TI - Protein Folding in Classical Perspective: Folding of Horse Cytochrome c VL - 44 SP - 3034 KW - folding KW - kinetics AU - Bhuyan, AK AU - Rao, DK AU - Prabhu, NP PY - 2005/03/01/ UR - http://dx.doi.org/10.1021/bi047897n ER -