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Protein folding in classical perspective: folding of horse cytochrome c.
Biochemistry. 2005 Mar 01; 44(8):3034-40.B

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 k(B)T. 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.

Authors+Show Affiliations

School of Chemistry, University of Hyderabad, Hyderabad 500046, India. akbsc@uohyd.ernet.inNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15723547

Citation

Bhuyan, Abani K., et al. "Protein Folding in Classical Perspective: Folding of Horse Cytochrome C." Biochemistry, vol. 44, no. 8, 2005, pp. 3034-40.
Bhuyan AK, Rao DK, Prabhu NP. Protein folding in classical perspective: folding of horse cytochrome c. Biochemistry. 2005;44(8):3034-40.
Bhuyan, A. K., Rao, D. K., & Prabhu, N. P. (2005). Protein folding in classical perspective: folding of horse cytochrome c. Biochemistry, 44(8), 3034-40.
Bhuyan AK, Rao DK, Prabhu NP. Protein Folding in Classical Perspective: Folding of Horse Cytochrome C. Biochemistry. 2005 Mar 1;44(8):3034-40. PubMed PMID: 15723547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein folding in classical perspective: folding of horse cytochrome c. AU - Bhuyan,Abani K, AU - Rao,D Krishna, AU - Prabhu,N Prakash, PY - 2005/2/23/pubmed PY - 2005/4/19/medline PY - 2005/2/23/entrez SP - 3034 EP - 40 JF - Biochemistry JO - Biochemistry VL - 44 IS - 8 N2 - 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 k(B)T. 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. SN - 0006-2960 UR - https://www.unboundmedicine.com/medline/citation/15723547/Protein_folding_in_classical_perspective:_folding_of_horse_cytochrome_c_ DB - PRIME DP - Unbound Medicine ER -