NR AKHS
AU Safar,J.G.; Ceroni,M.; Gajdusek,D.C.; Gibbs,C.J.Jr.
TI Differences in the membrane interaction of scrapie amyloid precursor proteins in normal and scrapie- or Creutzfeldt-Jakob disease-infected brains
QU Journal of Infectious Diseases 1991 Mar; 163(3): 488-94
PT journal article
AB 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.
MH Animal; Brain/*metabolism; Creutzfeldt-Jakob Syndrome/*metabolism; Endopeptidases/metabolism; Female; Glycolipids/metabolism; Hamsters; Human; Male; Mesocricetus; PrPc Proteins; PrPsc Proteins; Protein Precursors/*metabolism; Reference Values; Scrapie/*metabolism; Synaptic Membranes/*metabolism; Viral Proteins/*metabolism
AD Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
SP englisch
PO USA