Rapid folding of the prion protein captured by pressure-jump |
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Authors: | David C. Jenkins David S. Pearson Andrew Harvey Ian D. Sylvester Michael A. Geeves Teresa J. T. Pinheiro |
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Affiliation: | (1) Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK;(2) Department of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, UK |
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Abstract: | The conversion of the cellular form of the prion protein (PrPC) to an altered disease state, generally denoted as scrapie isoform (PrPSc), appears to be a crucial molecular event in prion diseases. The details of this conformational transition are not fully understood, but it is perceived that they are associated with misfolding of PrP or its incapacity to maintain the native fold during its cell cycle. Here we present a tryptophan mutant of PrP (F198W), which has enhanced fluorescence sensitivity to unfolding/refolding transitions. Equilibrium folding was studied by circular dichroism and fluorescence. Pressure-jump experiments were successfully applied to reveal rapid submillisecond folding events of PrP at temperatures not accessed before. D. C. Jenkins and D. S. Pearson contributed equally. |
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Keywords: | Prion folding Folding intermediate Pressure-jump Tryptophan mutant Folding kinetics Prion conversion |
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