Methionine sulfoxides on Pr[P.sup.Sc]: a prion-specific covalent signature

The unique recognition properties of [alpha]PrP mAb IPC2, protein chemistry and state of the art mass spectrometry are used for showing that while a large fraction of the methionine residues in brain Pr[P.sup.Sc] are present as methionine sulfoxides this modification could not be found on brain Pr[P.sup.C] as well as on its recombinant models. The results have shown that accumulation of Pr[P.sup.Sc] and thereafter the pathogenesis of prion disease has resulted from the poor degradation of oxidized aberrantly folded PrP.