Gs. Jackson et al., Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations, SCIENCE, 283(5409), 1999, pp. 1935-1937
Prion propagation involves the conversion of cellular prion protein (PrPc)
into a disease-specific isomer, PrPSc, shifting from a predominantly alpha-
helical to beta-sheet structure. Here, conditions were established in which
recombinant human PrP could switch between the native a conformation, char
acteristic of PrPc, and a compact, highly soluble, monomeric form rich in b
eta structure. The soluble beta form (beta-PrP) exhibited partial resistanc
e to proteinase kappa digestion, characteristic of PrPSc, and was a direct
precursor of fibrillar structures closely similar to those isolated from di
seased brains. The conversion of PrPc to beta-PrP in suitable cellular comp
artments, and its subsequent stabilization by intermolecular association, p
rovide a molecular mechanism for prion propagation.