The heterogeneity of the clinicopathological phenotype in human prion diseases is associated with the presence of the different forms of the abnormal prion protein, PrPSc. We have previously shown that PrPSc in FFI and a subtype of familial CJD linked to the D178N mutation can be distinguished by their difference in gel mobility following proteinase K (PK) treatment. To further characterize the structural difference of PrPSc in familial prion diseases, N-terminal sequencing and mass spectrometry were used to identify the protease cleavage sites in PrPSc extracted from affected brains. We found that the main PK cleavage sites of PrPSc are located at residue 97 in FFI, and residue 82 in both CJD178 and a GSS subtype linked to the P102L mutation. The differential accessibility to protease in the native PrPSc suggests that PrPSc exist as distinct conformers in different disease states.
|Number of pages||8|
|Journal||Archives of virology. Supplementum|
|Publication status||Published - 2001|
ASJC Scopus subject areas
- Immunology and Microbiology(all)