Methionine oxidation inhibits fibrillation of human α‐synuclein in vitro

FEBS Letters

Glaser, Charles B¹  Souillac, Pierre O²  Fink, Anthony L²  Goers, John²  Uversky, Vladimir N²  Yamin, Ghiam² 

[1] 307 Greene Street, Mill Valley, CA 94941, USA;Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA

关键词: Parkinson's disease;    α-Synuclein;    Oxidative stress;    Methionine oxidation;    Fibrillation;    Inhibition of fibrillation;    Partially folded intermediate;   

DOI  :  10.1016/S0014-5793(02)02638-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown