PrP Sc -Specific Antibody Reveals C-Terminal Conformational Differences between Prion Strains

Abstract

ABSTRACT Understanding the structure of PrP Sc and its strain variation has been one of the major challenges in prion disease biology. To study the strain-dependent conformations of PrP Sc , we purified proteinase-resistant PrP Sc (PrP RES ) from mouse brains with three different murine-adapted scrapie strains (Chandler, 22L, and Me7) and systematically tested the accessibility of epitopes of a wide range of anti-PrP and anti-PrP Sc specific antibodies by indirect enzyme-linked immunosorbent assay (ELISA). We found that epitopes of most anti-PrP antibodies were hidden in the folded structure of PrP RES , even though these epitopes are revealed with guanidine denaturation. However, reactivities to a PrP Sc -specific conformational C-terminal antibody showed significant differences among the three different prion strains. Our results provide evidence for strain-dependent conformational variation near the C termini of molecules within PrP Sc multimers. IMPORTANCE It has long been apparent that prion strains can have different conformations near the N terminus of the PrP Sc protease-resistant core. Here, we show that a C-terminal conformational PrP Sc -specific antibody reacts differently to three murine-adapted scrapie strains. These results suggest, in turn, that conformational differences in the C terminus of PrP Sc also contribute to the phenotypic distinction between prion strains.