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 °C and pH 7.0, folding
of mPrP(121−231)−F175W is too fast to be observable by
stopped-flow techniques. Folding at 4 °C occurs with a deduced half-life of
~170 s 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.
s 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.
