A CONFORMATIONAL TRANSITION AT THE N-TERMINUS OF THE PRION PROTEIN FEATURES IN FORMATION OF THE SCRAPIE ISOFORM

The scrapie prion protein (PrPSc) is formed from the cellular isoform (PrPC) by a post-translational process that involves a profound confor mational change. Linear epitopes for recombinant antibody Fab fragment s (Fabs) on PrPC and on the protease-resistant core of PrPSc, designat ed PrP 27-30, were identified using ELISA and immunoprecipitation. An epitope region at the C terminus was accessible in both PrPC and PrP 2 7-30; in contrast, epitopes towards the N-terminal region (residues 90 to 120) were accessible in PrPC but largely cryptic in PrP 27-30. Den atruation of PrP 27-30 exposed the epitopes of the N-terminal domain. We argue from our findings that the major conformational change underl ying PrPSc formation occurs within the N-terminal segment of PrP 27-30 . (C) 1997 Academic Press Limited.