Isolation of Isoforms of Mouse Prion Protein with PrPSC-like Structural Properties

Abstract

Three novel conformational isomers of mouse prion protein mPrP(23−231) were prepared by incubating the reduced mPrP(23−231) in the presence of urea at mild acidic conditions. They are stable isomers that can be separated and isolated by reversed phase HPLC. These isomers, designated mPrP-a, mPrP-b, and mPrP-c, all exist in reduced state and monomeric form. They all exhibit a high content of β-sheet structure upon oligomerization at near-neutral pH. They are also partially resistant to proteolysis by proteinase K and chymotrypsin. These structural properties are hallmarks of pathogenic prion protein (PrP^SC).