Lipid interaction of α-synuclein during the metal-catalyzed oxidation in the presence of Cu2+ and H2O2

摘要: α-Synuclein co-exists with lipids in the Lewy bodies, a pathological hallmark of Parkinson's disease. Molecular interaction between α-synuclein and has been examined by observing lipid-induced protein self-oligomerization presence chemical coupling reagent N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline. Lipids such as phosphatidic acid, phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine, even arachidonic acid induced whereas phosphatidylcholine did not affect protein. Because oligomerizations occurred from critical micelle concentrations lipids, self was shown to be lipid-surface dependent phenomenon head group specificity. By employing β-synuclein C-terminally truncated (α-syn97), head-group demonstrated occur preferentially at N-terminal region while fatty leading self-association required acidic C-terminus α-synuclein. In Cu2+ H2O2, phosphatidylinositol (PI), along other actually enhanced metal-catalyzed oxidative The dityrosine crosslink formation responsible for PI-enhanced covalent more sensitive variation copper than that H2O2 during oxidation. enhancement PI due facilitation localization because actual binding affinity increased Kd 44.7 μm 5.9 μm lipid. Taken together, only affects self-interactive providing lipid surface, but also enhances facilitating when metal are provided. This observation therefore could implicated bodies stress have considered part causes neurodegeneration.