Importance of dynamical processes in the coordination chemistry and redox conversion of copper amyloid-β complexes
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Interaction of Cu ions with the amyloid-β (Aβ) peptide is linked to the development of Alzheimer’s disease; hence, determining the coordination of CuI and CuII ions to Aβ and the pathway of the CuI(Aβ)/CuII(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 CuI and CuII complexes are similar to those previously determined from frozen-solution studies. More precisely, the CuI 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 CuI 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.
KeywordsCopper Ligand binding Peptide NMR Electrochemistry
Extended X-ray absorption fine structure
Reactive oxygen species
Saturated calomel electrode
X-ray absorption spectroscopy
X-ray absorption near edge structure
This work was supported by a grant from the Agence Nationale de la Recherche, Programme Blanc (NT09-488591, “NEUROMETALS”). The staff of the SAMBA beamline at SOLEIL (SOLEIL Project 20080324) is gratefully acknowledged for help in performing the XAS experiments. We acknowledge Emmanuelle Mothes for technical assistance and Pierre Dorlet for fruitful discussions.