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Biochemistry. 2011 Aug 23;50(33):7077-9. doi: 10.1021/bi200750k. Epub 2011 Jul 26.

Native-state interconversion of a metamorphic protein requires global unfolding.

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1
Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

Abstract

Lymphotactin (Ltn) is a unique chemokine that under physiological solution conditions displays large-scale structural heterogeneity, defining a new category of "metamorphic proteins". Previous Ltn studies have indicated that each form is required for proper function, but the mechanism of interconversion remains unknown. Here we have investigated the temperature dependence of kinetic rates associated with interconversion and unfolding by stopped-flow fluorescence to determine transition-state free energies. Comparisons of derived thermodynamic parameters revealed striking similarities between interconversion and protein unfolding. We conclude that Ltn native-state rearrangement proceeds by way of a large-scale unfolding process rather than a unique intermediate structure.

PMID:
21776971
PMCID:
PMC3160782
DOI:
10.1021/bi200750k
[Indexed for MEDLINE]
Free PMC Article
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