title: Extremely rapid folding of the C-terminal domain of the prion protein without kinetic intermediates.
abstract: The kinetics of folding of mPrP(121-231), the structured 111-residue domain of the murine cellular prion protein PrP(C), were investigated by stopped-flow fluorescence using the variant F175W, which has the same overall structure and stability as wild-type mPrP(121-231) but shows a strong fluorescence change upon unfolding. At 22 degrees C and pH 7.0, folding of mPrP(121-231)-F175W is too fast to be observable by stopped-flow techniques. Folding at 4 degrees C occurs with a deduced half-life of approximately 170 micros without detectable intermediates, possibly the fastest protein-folding reaction known so far. Thus, propagation of the abnormal, oligomeric prion protein PrP(Sc), which is supposed to be the causative agent of transmissible spongiform encephalopathies, is unlikely to follow a mechanism where kinetic folding intermediates of PrP(C) are a source of PrP(Sc) subunits.
authors.affiliation: Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Hönggerberg, Zürich, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Wildegger
authors.forename: S
authors.initials: S
authors.lastname: Liemann
authors.forename: R
authors.initials: R
authors.lastname: Glockshuber
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002942:Circular Dichroism; D004220:Disulfides; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014508:Urea
chemical_list: D004220:Disulfides; D010446:Peptide Fragments; D011328:Prions; D011994:Recombinant Proteins; C100569:prion protein (121-231); D014364:Tryptophan; D014508:Urea