Seeded conversion of recombinant prion protein to a disulfide-bonded oligomer by a reduction-oxidation process

The infectious form of prion protein, PrP^Sc, self-propagates by its conversion of the normal, cellular prion protein molecule PrP^C to another PrP^Sc molecule. It has not yet been demonstrated that recombinant prion protein can convert prion protein molecules from PrP ^C to PrP^Sc. Here we show that recombinant hamster prion protein is converted to a second form, PrP^RDX, by a redox process in vitro and that this PrP^RDX form seeds the conversion of other PrP^C molecules to the PrP^RDX form. The converted form shows properties of oligomerization and seeded conversion that are characteristic of PrP^Sc. We also find that the oligomerization can be reversed in vitro. X-ray fiber diffraction suggests an amyloid-like structure for the oligomerized prion protein. A domain-swapping model involving intermolecular disulfide bonds can account for the stability and coexistence of two molecular forms of prion protein and the capacity of the second form for self-propagation.