Site-specific interaction between ?-synuclein and membranes probed by NMR-observed methionine oxidation rates.
Related Articles Site-specific interaction between ?-synuclein and membranes probed by NMR-observed methionine oxidation rates.
J Am Chem Soc. 2013 Feb 11;
Authors: Maltsev AS, Chen J, Levine RL, Bax A
Abstract
?-Synuclein (aS) 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 eukaroytic cells. In the presence of lipid vesicles containing a small fraction of peroxidized lipids, the N-terminal Met residues in aS (Met1 and Met5) rapidly oxidize while reducing the toxic lipid hydroperoxide to a non-reactive lipid hydroxide, whereas C-terminal Met residues remain unaffected. Met oxidation can be probed conveniently and quantitatively by NMR spectroscopy. Results show that oxidation of Met1 reduces the oxidation rate of Met5, and vice versa, caused by decreased membrane affinity of the partially oxidized protein. The effect of Met oxidation on aS-membrane affinity extends over large distances, with the oxidation rate of Met49 in the V49M mutant of aS being strongly impacted by oxidation states of Met1 and Met5, and inversely the oxidation state of Met49 affecting the oxidation rates of the N-terminal Met residues. When not bound to membrane, oxidized Met1 and Met5 of aS 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.
PMID: 23398174 [PubMed - as supplied by publisher]
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