Prion Protein Conformation in a Patient with Sporadic Fatal Insomnia

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Abstract
The human prion diseases include Creutzfeldt–Jakob disease, Gerstmann–Sträussler–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 in humans and animals with prion disease. The relative molecular mass of the protease-resistant segment varies among prion strains and appears to be coupled with or associated with disease-specific phenotypes.5,6