Residues surrounding the glycosylphosphatidylinositol anchor attachment site of PrP modulate prion infection: Insight from the resistance of rabbits to prion disease

Abstract

Prion diseases are a group of transmissible, invariably fatal neurodegenerative diseases that affect both humans and animals. According to the protein-only hypothesis, the infectious agent is a prion (proteinaceous infectious particle) that is composed primarily of PrPSc, the disease-associated isoform of the cellular prion protein, PrP. PrPSc arises from the conformational change of the normal, glycosylphosphatidylinositol (GPI)-anchored protein, PrPC. The mechanism by which this process occurs, however, remains enigmatic. Rabbits are one of a small number of mammalian species reported to be resistant to prion infection. Sequence analysis of rabbit PrP revealed that its C-terminal amino aci..