Zinc binding to Alzheimer's A beta(1-16) peptide results in stable solublecomplex

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 o bligatory zinc binding site. However, time-dependent aggregation of the zin c-bound A beta species investigated so far prevented their structural analy sis. 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 bin ds specifically zinc with 1:1 and 1:2 stoichiometry under physiologically r elevant conditions; (ii) the peptide-zinc complex is soluble and stable for several months; (iii) zinc binding causes a conformational change of the p eptide 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 Ac ademic Press.