NR AJPP
AU Priola,S.A.; Caughey,B.W.; Wehrly,K.; Chesebro,B.
TI A 60-kDa prion protein (PrP) with properties of both the normal and scrapie-associated forms of PrP
QU The Journal of Biological Chemistry 1995 Feb 17; 270(7): 3299-305
PT journal article
AB Scrapie is a transmissible spongiform encephalopathy of sheep and other mammals in which disease appears to be caused by the accumulation of an abnormal form of a host protein, prion protein (PrP), in the brain and other tissues. The process by which the normal protease-sensitive form of PrP is converted into the abnormal protease-resistant form is unknown. Several hypotheses predict that oligomeric forms of either the normal or abnormal PrP may act as intermediates in the conversion process. We have now identified a 60-kDa PrP derived from hamster PrP expressed in murine neuroblastoma cells. Peptide mapping studies provided evidence that the 60-kDa PrP was composed solely of PrP and, based on its molecular mass, appeared to be a PrP dimer. The 60-kDa PrP was not dissociated under several harsh denaturing conditions, which indicated that it was covalently linked. It was similar to the disease-associated form of PrP in that it formed large aggregates. However, it resembled the normal form of PrP in that it was sensitive to proteinase K and had a short metabolic half-life. The 60-kDa PrP, therefore, had characteristics of both the normal and disease-associated forms of PrP. Formation and aggregation of the 60-kDa hamster PrP occurs in uninfected mouse neuroblastoma cells, which suggests that hamster PrP has a predisposition to aggregate even in the absence of scrapie infectivity. Similar 60-kDa PrP bands were identified in scrapie-infected hamster brain but not in uninfected brain. Therefore, a 60-kDa molecule might participate in the scrapie-associated conversion of protease-sensitive PrP to protease-resistant PrP.
IN In Hamsterprionprotein exprimierenden, nicht infizierten Mausneuroblastomzellen wurden offenbar kovalent gebundene 60 kD Prionproteindimere gefunden. Diese sind proteasesensibel und haben eine kurze Halbwertzeit, können aber größere Aggregate bilden. Solche Dimere wurden auch in scrapieinfizierten, aber nicht in normalen Hamstergehirnen gefunden.
ZR 50
MH Animal; Brain/*metabolism; Cell Line; Electrophoresis, Polyacrylamide Gel; Hamsters; Macromolecular Systems; Mammals; Mice; Molecular Weight; Neuroblastoma; Peptide Mapping; PrPsc Proteins/*biosynthesis/chemistry/isolation & purification; Prions/*biosynthesis/chemistry/isolation & purification; Recombinant Proteins/biosynthesis/chemistry/isolation & purification; Scrapie/*metabolism; Sheep; Transfection; Tumor Cells, Cultured
AD Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840.
SP englisch
PO USA