Publication 650

J. Biol. Inorg. Chem. 14, 995 -1000, 2009. DOI: 10.1007/s00775-009-0570-0
Importance of dynamical processes in the coordination chemistry and redox conversion of copper amyloid-b complexes.

CNRS; LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, 31077 Toulouse, France, Université de Toulouse; UPS, INPT; LCC;, 31077 Toulouse, France, Laboratoire d'Electrochimie Moléculaire, Université Paris Diderot, UMR CNRS 7591, 15, rue Jean-Antoine de Baïf, 75205 Paris Cedex 13, France, Synchrotron SOLEIL, L'Orme des Merisiers, BP48, Saint-Aubin, 91192 Gif-sur-Yvette Cedex, France

Interaction of Cu ions with the amyloid-β (Aβ) peptide is linked to the development of Alzheimer’s disease; hence, determining the coordination of Cu^I and Cu^II ions to Aβ and the pathway of the Cu^I(Aβ)/Cu^II(Aβ) redox conversion is of great interest. In the present report, we use the room temperature X-ray absorption near edge structure to show that the binding sites of the Cu^I and Cu^II complexes are similar to those previously determined from frozen-solution studies. More precisely, the Cu^I is coordinated by the imidazole groups of two histidine residues in a linear fashion. However, an NMR study unravels the involvement of all three histidine residues in the Cu^I binding due to dynamical exchange between several set of ligands. The presence of an equilibrium is also responsible for the complex redox process observed by cyclic voltammetry and evidenced by a concentration-dependent electrochemical response.