Functional and structural differences between the prion protein from two alleles prnp(a) and prnp(b) of mouse

The prion protein is a glycoprotein expressed by neurones and other cells. In its holo-form it binds copper and exhibits superoxide dismutase activity . Studies in mice have led to the description of two distinct alleles. Diff erences in these alleles are linked to long and short incubation times foll owing infection with scrapie. We studied recombinant mouse protein correspo nding to the products of either allele and two intermediates carrying singl e amino-acid residue substitutions. The different forms of the prion protei n exhibited differences in superoxide dismutase (SOD) activity and conforma tion. Intermediates with single substitutions were less stable than either allelic product. The findings provide insight into the differences between the two alleles and might have consequences for understanding differences i n susceptibility to prion disease.