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Rapid folding of the prion protein captured by pressure-jump.

ABSTRACT: The conversion of the cellular form of the prion protein (PrP(C)) to an altered disease state, generally denoted as scrapie isoform (PrP(Sc)), 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.

SUBMITTER: Jenkins DC

PROVIDER: S-EPMC4509520 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Rapid folding of the prion protein captured by pressure-jump.

Jenkins David C DC Pearson David S DS Harvey Andrew A Sylvester Ian D ID Geeves Michael A MA Pinheiro Teresa J T TJT

European biophysics journal : EBJ 20090303 5

The conversion of the cellular form of the prion protein (PrP(C)) to an altered disease state, generally denoted as scrapie isoform (PrP(Sc)), 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 sensi ...[more]

PMID: 19255752

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