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 CuII, but in vivo the protein is N-acetylated, and CuII binding is lost. We have now clarified the binding characteristics of the CuI 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 CuI-αS stoichiometry, where CuI is bound to Met1 and Met5 residues of two helical peptide chains. The resulting tetrahedral CuI 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 CuI-αS, which retains the capacity to activate O2 and promote oxidative reactions, membrane-bound CuI-αS may serve as a sink for unreactive copper.
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|Titolo:||Copper(I) Forms a Redox-Stable 1:2 Complex with α-Synuclein N-Terminal Peptide in a Membrane-Like Environment|
|Appare nelle tipologie:||1.1 Articolo in rivista|