Design of anti- and pro-aggregation variants to assess the effects of methionine oxidation in human prion protein.

ABSTRACT: Prion disease is characterized by the alpha-->beta structural conversion of the cellular prion protein (PrP(C)) into the misfolded and aggregated "scrapie" (PrP(Sc)) isoform. It has been speculated that methionine (Met) oxidation in PrP(C) may have a special role in this process, but has not been detailed and assigned individually to the 9 Met residues of full-length, recombinant human PrP(C) [rhPrP(C)(23-231)]. To better understand this oxidative event in PrP aggregation, the extent of periodate-induced Met oxidation was monitored by electrospray ionization-MS and correlated with aggregation propensity. Also, the Met residues were replaced with isosteric and chemically stable, nonoxidizable analogs, i.e., with the more hydrophobic norleucine (Nle) and the highly hydrophilic methoxinine (M

SUBMITTER: Wolschner C 

PROVIDER: S-EPMC2674404 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature