8 PRION STRAINS HAVE PRPSC MOLECULES WITH DIFFERENT CONFORMATIONS

Variations in prions, which cause different incubation times and depos ition patterns of the prion protein isoform called PrPSc, are often re ferred to as 'strains'. We report here a highly sensitive, conformatio n-dependent immunoassay that discriminates PrPSc molecules among eight different prion strains propagated in Syrian hamsters. This immunoass ay quantifies PrP isoforms by simultaneously following antibody bindin g to the denatured and native forms of a protein. In a plot of the rat io of antibody binding to denatured/native PrP graphed as a function o f the concentration of PrPSc, each strain occupies a unique position, indicative of a particular PrPSc conformation. This conclusion is supp orted by a unique pattern of equilibrium unfolding of PrPSc found with each strain. Our findings indicate that each of the eight prion strai ns has a PrPSc molecule with a unique conformation and, in accordance with earlier results, indicate the biological properties of prion stra ins are 'enciphered' in the conformation of PrPSc and that the variati on in incubation times is related to the relative protease sensitivity of PrPSc in each strain.