Methionine oxidation inhibits fibrillation of human alpha-synuclein in vitro.
We examined the effect of methionine oxidation of human recombinant alpha-synuclein on its structural properties and propensity to fibrillate. Both oxidized and non-oxidized alpha-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 alpha-synuclein at neutral pH was completely inhibited by methionine oxidation. This inhibitory effect was eliminated at low pH. The addition of oxidized alpha-synuclein to the unoxidized form led to a substantial inhibition of alpha-synuclein fibrillation.
Uversky
Vladimir N
VN
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA. uversky@hydrogen.ucsc.edu
Yamin
Ghiam
G
Souillac
Pierre O
PO
Goers
John
J
Glaser
Charles B
CB
Fink
Anthony L
AL
D004926:Escherichia coli; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008715:Methionine / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D008715:Methionine