Methionine oxidation inhibits fibrillation of human α‐synuclein in vitro

Abstract
We examined the effect of methionine oxidation of human recombinant α-synuclein on its structural properties and propensity to fibrillate. Both oxidized and non-oxidized α-synucleins were natively unfolded under conditions of neutral pH, with the oxidized protein being slightly more disordered. Both proteins adopted identical partially folded conformations under conditions of acidic pH. The fibrillation of α-synuclein at neutral pH was completely inhibited by methionine oxidation. This inhibitory effect was eliminated at low pH. The addition of oxidized α-synuclein to the unoxidized form led to a substantial inhibition of α-synuclein fibrillation.