Prion Protein Conformation in a Patient with Sporadic Fatal Insomnia

Abstract

The human prion diseases include Creutzfeldt–Jakob disease, Gerstmann–Straussler–Scheinker disease, fatal familial insomnia, and the recently described new variant of Creutzfeldt–Jakob disease. Much evidence argues that a post-translational, noncovalent modification of prion protein is the fundamental event in the mechanism underlying these diseases.1 The normal cellular isoform of the prion protein (PrPC) is predominantly α-helical, is detergent soluble, and is readily digested by proteases. In contrast, the pathogenic isoform (PrPSc) has a substantially β-sheet structure, is insoluble in nondenaturing detergents, and shows relative resistance to proteolytic digestion.2–4 The protease-resistant core of PrPSc, designated PrP27–30, is usually detectable . . .