title: 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.
authors.affiliation: Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Jenkins
authors.affiliation: Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
authors.forename: David S
authors.initials: DS
authors.lastname: Pearson
authors.affiliation: Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Harvey
authors.affiliation: Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Sylvester
authors.affiliation: Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Geeves
authors.affiliation: Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Teresa J T
authors.initials: TJT
authors.lastname: Pinheiro
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D006224:Cricetinae; D007700:Kinetics; D008647:Mesocricetus; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011312:Pressure; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011489:Protein Denaturation; D017510:Protein Folding; D020673:Protein Renaturation; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013816:Thermodynamics
chemical_list: D010446:Peptide Fragments; D011328:Prions