Differences in the membrane interaction of scrapie amyloid precursor proteins in normal and scrapie- or Creutzfeldt-Jakob disease-infected brains.
The membrane interaction and hydrophobicity of the normal (PrPC) and infectious isoform (PrPSc/CJD) of scrapie and Creutzfeldt-Jakob disease amyloid precursor proteins was studied. The normal isoform of hamster and human scrapie amyloid precursor protein was found on the microsomal/synaptosomal membranes anchored solely by the C-terminal glycolipid. Glycolipid cleavage resulted in dissociation from the membranes and change of behavior from a highly hydrophobic to a hydrophilic protein, susceptible to proteases. In contrast, the PrPSc/CJD isoform was resistant to release by glycolipid-cleaving enzymes. A part of PrPSc/CJD was released from the membranes after prolonged trypsin treatment, yielding a further protease-resistant product of 27-30 kDa. The results demonstrate the proteolytic resistance of the membrane-bound PrPSc/CJD isoform and also indicate the presence of a different, apparently disease-induced mechanism of membrane interaction in the scrapie- and CJD-infected microsomal and synaptosomal membranes.
Safar
J
J
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Ceroni
M
M
Gajdusek
D C
DC
Gibbs
C J
CJ
D000818:Animals; D001921:Brain / Q000378:metabolism*; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism*; D006224:Cricetinae; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D008297:Male; D008647:Mesocricetus; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011498:Protein Precursors / Q000378:metabolism*; D012016:Reference Values; D012608:Scrapie / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
D006017:Glycolipids; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011498:Protein Precursors; D014764:Viral Proteins; D010450:Endopeptidases