Changing the transition state for protein (Un) folding

Biochemistry
D F DoyleG J Pielak

Abstract

(Un)folding transition states of Saccharomyces cerevisiae iso-1-ferri- and ferrocytochromes c were studied using equilibrium and kinetic denaturation experiments. The wild-type protein and the global suppressor variant, N52I (isoleucine replaces asparagine 52), were examined. Denaturation was induced by guanidinium chloride (GdmCI) and monitored by circular dichroism (CD) spectropolarimetry without stopped-flow devices. Soret CD spectra indicate that thermal and GdmCl denatured states are different, and heat is the more effective denaturant. Equilibrium data show that the high stability of ferrocytochrome c can be rationalized as a requirement to bury the oxidation-induced positive charge and remain folded under physiological conditions. Kinetic data are monoexponential and permit characterization of the rate-limiting transition state for unfolding as a function of [GdmCl]. For the oxidized wild-type protein, the transition state solvent accessibility is nearly the same as that of the denatured state. Three perturbations, reducing the wild-type protein, reducing the N52I variant, and substituting position 52 in the oxidized protein, change the free energy and solvent accessibility of the transition state. In contrast, substitut...Continue Reading

Citations

May 30, 1998·Protein Science : a Publication of the Protein Society·W A McGee, B T Nall
Nov 26, 2008·Nature Cell Biology·Allyson E Vaughn, Mohanish Deshmukh
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Related Concepts

CYC1 protein, S cerevisiae
Asparagine
Calorimetry
Circular Dichroism, Vibrational
Cytochrome c Group
Guanidines
Alloisoleucine
Oxidation-Reduction
Protein Conformation
Protein Denaturation

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