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Daniel Otzen

Correspondence between anomalous m- and ΔCp-values in protein folding

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Correspondence between anomalous m- and ΔCp-values in protein folding. / Otzen, Daniel E.; Oliveberg, Mikael.

In: Protein Science, Vol. 13, No. 12, 01.12.2004, p. 3253-3263.

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Otzen, Daniel E. ; Oliveberg, Mikael. / Correspondence between anomalous m- and ΔCp-values in protein folding. In: Protein Science. 2004 ; Vol. 13, No. 12. pp. 3253-3263.

Bibtex

@article{d195a0fb108f4442857c74aff0b1c8ab,
title = "Correspondence between anomalous m- and ΔCp-values in protein folding",
abstract = "Proteins folding according to a classical two-state system characteristically show V-shaped chevron plots. We have previously interpreted the symmetrically curved chevron plot of the protein U1A as denaturant-dependent movements in the position of the transition state ensemble (TSE). S6, a structural analog of U1A, shows a classical V-shaped chevron plot indicative of straightforward two-state kinetics, but the mutant LA30 has a curved unfolding limb, which is most consistent with TSE mobility. The kinetic m-values (derivatives of the rate constants with respect to denaturant concentration) in themselves depend on denaturant concentration. To obtain complementary information about putative mobile TSEs, we have carried out a thermodynamic analysis of the three proteins, based on data for refolding and unfolding over the range 10°C to 70°C. The data at all temperatures can be fitted to two-state model systems. Importantly, for all three proteins the activation heat capacities are, within error, identical to the heat capacities measured in independent experiments under equilibrium conditions. Although the equilibrium heat capacities are essentially invariant with regard to denaturant concentration, the activation heat capacities, similar to the structurally equivalent kinetic m-values, show marked denaturant dependence. Furthermore, the values of β‡ at different denaturant concentrations measured by m-values and by heat capacity values are very similar. These observations are consistent with significant transition state movements within the framework of two-state folding. The basis for TSE movement appears to be enthalpic rather than entropic, suggesting that the binding energy of denaturant-protein interactions is a major determinant of the response of energy landscape contours to changing environments.",
keywords = "Heat capacity, Kinetics, M-values, Protein folding, Thermodynamics, Transition state ensemble",
author = "Otzen, {Daniel E.} and Mikael Oliveberg",
year = "2004",
month = dec,
day = "1",
doi = "10.1110/ps.04991004",
language = "English",
volume = "13",
pages = "3253--3263",
journal = "Protein Science",
issn = "0961-8368",
publisher = "Wiley-Blackwell Publishing, Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - Correspondence between anomalous m- and ΔCp-values in protein folding

AU - Otzen, Daniel E.

AU - Oliveberg, Mikael

PY - 2004/12/1

Y1 - 2004/12/1

N2 - Proteins folding according to a classical two-state system characteristically show V-shaped chevron plots. We have previously interpreted the symmetrically curved chevron plot of the protein U1A as denaturant-dependent movements in the position of the transition state ensemble (TSE). S6, a structural analog of U1A, shows a classical V-shaped chevron plot indicative of straightforward two-state kinetics, but the mutant LA30 has a curved unfolding limb, which is most consistent with TSE mobility. The kinetic m-values (derivatives of the rate constants with respect to denaturant concentration) in themselves depend on denaturant concentration. To obtain complementary information about putative mobile TSEs, we have carried out a thermodynamic analysis of the three proteins, based on data for refolding and unfolding over the range 10°C to 70°C. The data at all temperatures can be fitted to two-state model systems. Importantly, for all three proteins the activation heat capacities are, within error, identical to the heat capacities measured in independent experiments under equilibrium conditions. Although the equilibrium heat capacities are essentially invariant with regard to denaturant concentration, the activation heat capacities, similar to the structurally equivalent kinetic m-values, show marked denaturant dependence. Furthermore, the values of β‡ at different denaturant concentrations measured by m-values and by heat capacity values are very similar. These observations are consistent with significant transition state movements within the framework of two-state folding. The basis for TSE movement appears to be enthalpic rather than entropic, suggesting that the binding energy of denaturant-protein interactions is a major determinant of the response of energy landscape contours to changing environments.

AB - Proteins folding according to a classical two-state system characteristically show V-shaped chevron plots. We have previously interpreted the symmetrically curved chevron plot of the protein U1A as denaturant-dependent movements in the position of the transition state ensemble (TSE). S6, a structural analog of U1A, shows a classical V-shaped chevron plot indicative of straightforward two-state kinetics, but the mutant LA30 has a curved unfolding limb, which is most consistent with TSE mobility. The kinetic m-values (derivatives of the rate constants with respect to denaturant concentration) in themselves depend on denaturant concentration. To obtain complementary information about putative mobile TSEs, we have carried out a thermodynamic analysis of the three proteins, based on data for refolding and unfolding over the range 10°C to 70°C. The data at all temperatures can be fitted to two-state model systems. Importantly, for all three proteins the activation heat capacities are, within error, identical to the heat capacities measured in independent experiments under equilibrium conditions. Although the equilibrium heat capacities are essentially invariant with regard to denaturant concentration, the activation heat capacities, similar to the structurally equivalent kinetic m-values, show marked denaturant dependence. Furthermore, the values of β‡ at different denaturant concentrations measured by m-values and by heat capacity values are very similar. These observations are consistent with significant transition state movements within the framework of two-state folding. The basis for TSE movement appears to be enthalpic rather than entropic, suggesting that the binding energy of denaturant-protein interactions is a major determinant of the response of energy landscape contours to changing environments.

KW - Heat capacity

KW - Kinetics

KW - M-values

KW - Protein folding

KW - Thermodynamics

KW - Transition state ensemble

UR - http://www.scopus.com/inward/record.url?scp=9344266328&partnerID=8YFLogxK

U2 - 10.1110/ps.04991004

DO - 10.1110/ps.04991004

M3 - Journal article

C2 - 15557266

AN - SCOPUS:9344266328

VL - 13

SP - 3253

EP - 3263

JO - Protein Science

JF - Protein Science

SN - 0961-8368

IS - 12

ER -