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The major polypeptide of scrapie‐associated fibrils (SAF) has the same size, charge distribution and N‐terminal protein sequence as predicted for the normal brain protein (PrP).
Author(s) -
Hope J.,
Morton L.J.,
Farquhar C.F.,
Multhaup G.,
Beyreuther K.,
Kimberlin R.H.
Publication year - 1986
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1986.tb04539.x
Subject(s) - scrapie , fibril , biology , sequence (biology) , library science , computer science , prion protein , genetics , pathology , medicine , disease
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.