NR AMMR
AU Wildegger,G.; Liemann,S.; Glockshuber,R.
TI Extremely rapid folding of the C-terminal domain of the prion protein without kinetic intermediates
QU Nature Structural Biology 1999 Jun; 6(6): 550-3
PT journal article
AB The kinetics of folding of mPrP(121-231), the structured 111-residue domain of the murine cellular prion protein PrPc, 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 PrPsc, which is supposed to be the causative agent of transmissible spongiform encephalopathies, is unlikely to follow a mechanism where kinetic folding intermediates of PrPc are a source of PrPsc subunits.
MH Amino Acid Substitution; Animal; Circular Dichroism; Disulfides; Half-Life; Hydrogen-Ion Concentration; Kinetics; Mice; Models, Molecular; Peptide Fragments/*chemistry/metabolism; Prions/*chemistry/metabolism; Protein Conformation; *Protein Folding; Recombinant Proteins/chemistry/metabolism; Spectrometry, Fluorescence; Support, Non-U.S. Gov't; Temperature; Thermodynamics; Tryptophan/chemistry/genetics/metabolism; Urea
AD Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Hönggerberg, Zürich, Switzerland.
SP englisch
PO USA