異常プリオン分解酵素の機能解明(物質生命化学科)

Abstract

Prion diseases are characterized by conversion of the normal cellular form of the prion protein (PrP^C) into an insoluble, protease-resistant abnormal form (PrP^<Sc>). The aberrant isoform of PrP^C, PrP^<Sc>, which is characterized by relative resistance to proteolysis and insolubility in nondenaturing detergents, is a hallmark of prion diseases. There have been some reports of PrP^<Sc>-degrading enzymes, but these enzymes need additional chemical and physical treatments for the degradation of PrP^<Sc>. A keratinolytic alkaline serine protease (NAPase) from Nocardiopsis sp. TOA-1 degraded a PrP^<Sc> without any chemical or physical treatment. Optimal temperature and pH were 50-70℃ and above pH 10.0. The PrP^<Sc> was completely degraded within several minutes under optimal conditions. These results suggest NAPase have remarkable ability as PrP^<Sc>-degrading enzyme. The mechanism of PrP^<Sc>-degrading was investigated using PrP^<Sc>-model protein PSP (perchloric-acid soluble protein) from pig liver.