Eight prion strains have PrPSc molecules with different conformations

Abstract

Variations in prions, which cause different incubation times and deposition patterns of the prion protein isoform called PrP ^Sc , are often referred to as 'strains'. We report here a highly sensitive, conformation-dependent immunoassay that discriminates PrP ^Sc molecules among eight different prion strains propagated in Syrian hamsters. This immunoassay quantifies PrP isoforms by simultaneously following antibody binding to the denatured and native forms of a protein. In a plot of the ratio of antibody binding to denatured/native PrP graphed as a function of the concentration of PrP ^Sc , each strain occupies a unique position, indicative of a particular PrP ^Sc conformation. This conclusion is supported by a unique pattern of equilibrium unfolding of PrP ^Sc found with each strain. Our findings indicate that each of the eight prion strains has a PrP ^Sc molecule with a unique conformation and, in accordance with earlier results, indicate the biological properties of prion strains are 'enciphered' in the conformation of PrP ^Sc and that the variation in incubation times is related to the relative protease sensitivity of PrP ^Sc in each strain.