The N-terminal cleavage site of PrPSc from BSE differs from that of PrPSc from scrapie.

Heterogeneity in transmissible spongiform encephalopathy is thought to have derived from conformational variation in an abnormal isoform of the prion protein (PrPSc). To characterize PrPSc in bovine spongiform encephalopathy (BSE) and scrapie, we analyzed the newly generated N-terminus of PrPSc isoforms by digestion with proteinase K (PK). With a lower concentration of PK, the terminal amino acid of BSE PrPSc converged at N96. Under the same conditions, however, the terminal amino acid of scrapie PrPSc was G81 or G85. Furthermore, with an increase of PK concentration, the N-terminal amino acid was shifted and converged at G89. The results suggest that the PK cleavage site of BSE PrPSc is uniform and is different from the cleavage site of scrapie PrPSc.