Zinc-mediated modulation of the configuration and activity of complexes between copper and amyloid-β peptides.

A growing body of Alzheimer's disease (AD) research is concerned with understanding the interaction between amyloid-β (Aβ) peptides and metal ions (e.g., Cu, Zn, and Fe) and determining the biological relevance of the metal-Aβ complexes to essential metal homeostasis and neuronal cell loss. Previously, many studies have dealt with the interaction between Aβ and "single" but not "multiple" metal ions in terms of binding affinity and coordination chemistry. In the present work, we found that Zn(II) ions modified the configuration of Aβ-Cu(II) by forming Zn(II)-Aβ-Cu(II) ternary complexes. As a result, the catalytic activity of Aβ-Cu(II) against a biological ascorbic acid species was repressed by Zn(II) binding. The formation of the ternary complex can therefore explain the protective role of Zn(II) in AD.