Scrapie-associated fibrils (
SAF) are unique structures characteristic of the group of unconventional slow
infections which includes
scrapie and
Creutzfeldt-Jakob disease. A major component of hamster fibrils has been described as a
protease-resistant
glycoprotein with an apparent mol. wt of 27,000-30,000 (PrP27-30). However, we report here that if fibrils are prepared by procedures designed to minimise proteolysis the
PrP proteins co-purifying with hamster
SAF have mol. wts of 33,000-35,000 (PrP33-35) and 26,000-29,000 (PrP26-29). We find a
Lys-Lys-
Arg-Pro-Lys sequence at the amino terminus of these
SAF proteins, that is absent from PrP27-30, and which has recently been predicted to be the N-terminal sequence of the native PrP
protein of uninfected brain. The major
SAF protein (PrP33-35) and its normal brain homologue are shown to have the same apparent mol. wt and ionic charge distribution by two-dimensional gel analysis,
silver staining and immunoblotting. These results support our view that PrP33-35 and the normal brain PrP
protein may have the same covalent structure, and that the PrP
protein is recruited into these
amyloid-like
SAF or into association with a non-
protein component of
SAF by an irreversible event initiated directly or indirectly by
scrapie infection.