Iron(II) Binding to Amyloid-β, the Alzheimer’s Peptide

Abstract

Iron has been implicated in Alzheimer’s disease, but until now no direct proof of Fe^II binding to the amyloid-β peptide (Aβ) has been reported. We used NMR to evidence Fe^II coordination to full-length Aβ40 and truncated Aβ16 peptides at physiological pH and to show that the Fe^II binding site is located in the first 16 amino-acid residues. Fe^II caused selective broadening of some NMR peaks that was dependent on the Fe:Aβ stoichiometry and temperature. Analysis of Fe^II broadening effect in the ¹H, ¹³C, and 2D NMR data established that Asp1, Glu3, the three His, but not Tyr10 nor Met35 are the residues mainly involved in Fe^II coordination.