Copper(I) Forms a Redox-Stable 1:2 Complex with α-Synuclein N-Terminal Peptide in a Membrane-Like Environment

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• 作者：Simone Dell’Acqua ; Valentina Pirota ; Enrico Monzani ; Francesca Camponeschi ; Riccardo De Ricco ; Daniela Valensin ; Luigi Casella
• 刊名：Inorganic Chemistry
• 出版年：2016
• 出版时间：June 20, 2016
• 年：2016
• 卷：55
• 期：12
• 页码：6100-6106
• 全文大小：473K
• 年卷期：0
• ISSN：1520-510X

文摘

α-Synuclein (αS) is the main protein component of Lewy bodies, characterizing the pathogenesis of Parkinson’s disease. αS is unstructured in solution but adopts a helical structure in its extended N-terminal segment upon association with membranes. In vitro the protein binds avidly Cu^II, but in vivo the protein is N-acetylated, and Cu^II binding is lost. We have now clarified the binding characteristics of the Cu^I complex with the truncated αS peptide 1–15, both in N-acetylated and free amine forms, in a membrane mimetic environment and found that complexation occurs with a 1:2 Cu^I-αS stoichiometry, where Cu^I is bound to Met1 and Met5 residues of two helical peptide chains. The resulting tetrahedral Cu^I center is redox-stable, does not form reactive oxygen species, and is unreactive against dopamine in the presence of O₂. This suggests that, unlike cytosolic Cu^I-αS, which retains the capacity to activate O₂ and promote oxidative reactions, membrane-bound Cu^I-αS may serve as a sink for unreactive copper.