 -synuclein ( s ) is an intrinsically disordered 
 protein 
 that is water - soluble but also can bind negatively charged lipid membranes 
 while adopting an -helical conformation . 
 membrane affinity 
 is increased by post - translational n - terminal acetylation , a common 
 modification in all eukaryotic cells . in the presence of lipid vesicles 
 containing a small fraction of peroxidized lipids , the n - terminal 
 met residues in s ( met1 and met5 ) rapidly oxidize while reducing 
 the toxic lipid hydroperoxide to a nonreactive lipid hydroxide , whereas 
 c - terminal met residues remain unaffected . 
 met oxidation can be probed 
 conveniently and quantitatively by nmr spectroscopy . 
 the results show 
 that oxidation of met1 reduces the rate of oxidation of met5 and vice 
 versa as a result of decreased membrane affinity of the partially 
 oxidized protein . 
 the effect of met oxidation on the s  
 membrane 
 affinity extends over large distances , as in the v49 m mutant , oxidation 
 of met1 and met5 strongly impacts the oxidation rate of met49 and 
 vice versa . when not bound to membrane , 
 oxidized met1 and met5 of 
 s are excellent substrates for methionine sulfoxide reductase 
 ( msr ) , thereby providing an efficient vehicle for water - soluble msr 
 enzymes to protect the membrane against oxidative damage . 
Supplementary Material