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Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c

Kinetic studies of the early events in cytochrome c folding are reviewed with a focus on the evidence for folding intermediates on the submillisecond timescale. Evidence from time-resolved absorption, circular dichroism, magnetic circular dichroism, fluorescence energy and electron transfer, small-a...

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Autores principales: Goldbeck, Robert A., Chen, Eefei, Kliger, David S.
Formato: Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680628/
https://www.ncbi.nlm.nih.gov/pubmed/19468320
http://dx.doi.org/10.3390/ijms10041476
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author Goldbeck, Robert A.
Chen, Eefei
Kliger, David S.
author_facet Goldbeck, Robert A.
Chen, Eefei
Kliger, David S.
author_sort Goldbeck, Robert A.
collection PubMed
description Kinetic studies of the early events in cytochrome c folding are reviewed with a focus on the evidence for folding intermediates on the submillisecond timescale. Evidence from time-resolved absorption, circular dichroism, magnetic circular dichroism, fluorescence energy and electron transfer, small-angle X-ray scattering and amide hydrogen exchange studies on the t ≤ 1 ms timescale reveals a picture of cytochrome c folding that starts with the ~ 1-μs conformational diffusion dynamics of the unfolded chains. A fractional population of the unfolded chains collapses on the 1 – 100 μs timescale to a compact intermediate I(C) containing some native-like secondary structure. Although the existence and nature of I(C) as a discrete folding intermediate remains controversial, there is extensive high time-resolution kinetic evidence for the rapid formation of I(C) as a true intermediate, i.e., a metastable state separated from the unfolded state by a discrete free energy barrier. Final folding to the native state takes place on millisecond and longer timescales, depending on the presence of kinetic traps such as heme misligation and proline mis-isomerization. The high folding rates observed in equilibrium molten globule models suggest that I(C) may be a productive folding intermediate. Whether it is an obligatory step on the pathway to the high free energy barrier associated with millisecond timescale folding to the native state, however, remains to be determined.
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spelling pubmed-26806282009-05-22 Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c Goldbeck, Robert A. Chen, Eefei Kliger, David S. Int J Mol Sci Review Kinetic studies of the early events in cytochrome c folding are reviewed with a focus on the evidence for folding intermediates on the submillisecond timescale. Evidence from time-resolved absorption, circular dichroism, magnetic circular dichroism, fluorescence energy and electron transfer, small-angle X-ray scattering and amide hydrogen exchange studies on the t ≤ 1 ms timescale reveals a picture of cytochrome c folding that starts with the ~ 1-μs conformational diffusion dynamics of the unfolded chains. A fractional population of the unfolded chains collapses on the 1 – 100 μs timescale to a compact intermediate I(C) containing some native-like secondary structure. Although the existence and nature of I(C) as a discrete folding intermediate remains controversial, there is extensive high time-resolution kinetic evidence for the rapid formation of I(C) as a true intermediate, i.e., a metastable state separated from the unfolded state by a discrete free energy barrier. Final folding to the native state takes place on millisecond and longer timescales, depending on the presence of kinetic traps such as heme misligation and proline mis-isomerization. The high folding rates observed in equilibrium molten globule models suggest that I(C) may be a productive folding intermediate. Whether it is an obligatory step on the pathway to the high free energy barrier associated with millisecond timescale folding to the native state, however, remains to be determined. Molecular Diversity Preservation International (MDPI) 2009-04-01 /pmc/articles/PMC2680628/ /pubmed/19468320 http://dx.doi.org/10.3390/ijms10041476 Text en © 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Goldbeck, Robert A.
Chen, Eefei
Kliger, David S.
Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c
title Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c
title_full Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c
title_fullStr Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c
title_full_unstemmed Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c
title_short Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c
title_sort early events, kinetic intermediates and the mechanism of protein folding in cytochrome c
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680628/
https://www.ncbi.nlm.nih.gov/pubmed/19468320
http://dx.doi.org/10.3390/ijms10041476
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