Zinc binding to Alzheimer's Aβ(1-16) peptide results in stable soluble complex

Aggregation of the human amyloid beta -peptide (A,6) into insoluble plaques is a key event in Alzheimer's disease. Zinc sharply accelerates the A beta aggregation in vitro, and the A beta region 6-28 was suggested to be the obligatory zinc binding site. However, time-dependent aggregation of the zinc-bound A beta species investigated so far prevented their structural analysis. By using CD spectroscopy, we have shown here for the first time that (i) the protected synthetic peptide spanning the fragment 1-16 of A beta binds specifically zinc with 1:1 and 1:2 stoichiometry under physiologically relevant conditions; (ii) the peptide-zinc complex is soluble and stable for several months; (iii) zinc binding causes a conformational change of the peptide towards a more structured state. These findings suggest the region 1-16 to be the minimal autonomous zinc binding domain of A beta. (C) 2001 Academic Press.