NR AMXQ
AU Zanusso,G.; Farinazzo,A.; Fiorini,M.; Gelati,M.; Castagna,A.; Righetti,P.G.; Rizzuto,N.; Monaco,S.
TI pH-dependent prion protein conformation in classical Creutzfeldt-Jakob disease
QU The Journal of Biological Chemistry 2001 Nov 2; 276(44): 40377-80
PT journal article
AB In transmissible spongiform encephalopathies, the cellular prion protein (PrPc) undergoes a conformational change from a prevailing alpha-helical structure to a beta-sheet-rich, protease-resistant isoform, termed PrPsc. PrPc has two characteristics: a high affinity for Cu(2+) and a strong pH-dependent conformation. Lines of evidence indicate that PrPsc conformation is dependent on copper and that acidic conditions facilitate the conversion of PrPc -> PrPsc. In each species, PrPsc exists in multiple conformations, which are associated with different prion strains. In sporadic Creutzfeldt-Jakob disease (sCJD), different biochemical types of PrPsc have been identified according to the size of the protease-resistant fragments, patterns of glycosylation, and the metal-ion occupancy. Based on the site of cleavage produced by proteinase K, we investigated the conformational stability of PrPsc under acidic, neutral, and basic conditions in 42 sCJD subjects. Our study shows that only one type of sCJD PrPsc, associated with the classical form, shows a pH-dependent conformation, whereas two other biochemical PrPsc types, detected in distinct sCJD phenotypes, are unaffected by pH variations. This novel approach demonstrates the presence of three types of PrPsc in sCJD.
MH Blotting, Western; Creutzfeldt-Jakob Syndrome/*metabolism; Human; *Hydrogen-Ion Concentration; Prions/*chemistry/metabolism; Protein Conformation; Support, Non-U.S. Gov't
AD Department of Neurological and Visual Sciences, University of Verona, Piazzale L. A. Scuro, 10, 37134 Verona, Italy.
SP englisch
PO USA