Methionine-oxidized amyloid fibrils are poor substrates for human methionine sulfoxide reductases A and B2.
A common feature of many amyloid diseases is the appearance of oxidized, aggregated proteins. Methionine is one of the most readily oxidized amino acids, and its oxidative state is regulated in vivo by the methionine sulfoxide reductases (Msr). Here, we have explored the basis by which methionine oxidation is linked to amyloid disease by comparing the reduction of oxidized amyloid fibrils and monomer. We show that oxidized amyloid fibrils are not as effectively reduced by the Msr enzymes as the monomer. This work suggests a mechanism by which oxidized proteins and aggregates can accumulate as a part of degenerative disease.
Binger
Katrina J
KJ
Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria, Australia. katrinabinger@gmail.com
Griffin
Michael D W
MD
Heinemann
Stefan H
SH
Howlett
Geoffrey J
GJ
D000682:Amyloid / Q000737:chemistry*; D053304:Apolipoprotein C-II / Q000737:chemistry*; D006801:Humans; D008715:Methionine / Q000737:chemistry*; D051150:Methionine Sulfoxide Reductases / Q000737:chemistry*; D008840:Microfilament Proteins; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry*
D000682:Amyloid; D053304:Apolipoprotein C-II; D008840:Microfilament Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D008715:Methionine; D010088:Oxidoreductases; C120376:MSRB2 protein, human; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase