title: Oxidation of methionine residues in the prion protein by hydrogen peroxide.
abstract: Reaction of H(2)O(2) with the recombinant SHa(29-231) prion protein resulted in rapid oxidation of multiple methionine residues. Susceptibility to oxidation of individual residues, assessed by mass spectrometry after digestion with CNBr and lysC, was in general a function of solvent exposure. Met 109 and Met 112, situated in the highly flexible amino terminus, and key residues of the toxic peptide PrP (106-126), showed the greatest susceptibility. Met 129, a residue located in a polymorphic position in human PrP and modulating risk of prion disease, was also easily oxidized, as was Met 134. The structural effect of H(2)O(2)-induced methionine oxidation on PrP was studied by CD spectroscopy. As opposed to copper catalyzed oxidation, which results in extensive aggregation of PrP, this reaction led only to a modest increase in beta-sheet structure. The high number of solvent exposed methionine residues in PrP suggests their possible role as protective endogenous antioxidants.
authors.affiliation: Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. requenaj@usc.es
authors.forename: Jesús R
authors.initials: JR
authors.lastname: Requena
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Dimitrova
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Legname
authors.forename: Susana
authors.initials: S
authors.lastname: Teijeira
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Levine
mesh_terms: D000818:Animals; D001665:Binding Sites; D006224:Cricetinae; D006861:Hydrogen Peroxide / Q000737:chemistry*; D008647:Mesocricetus; D008715:Methionine / Q000737:chemistry*; D046912:Multiprotein Complexes / Q000737:chemistry; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D046912:Multiprotein Complexes; D010446:Peptide Fragments; D011328:Prions; D011994:Recombinant Proteins; D008715:Methionine; D006861:Hydrogen Peroxide