Binding of iron(III) to the single tyrosine residue of amyloid β-peptide probed by Raman spectroscopy

The Fe(III) ion binds to amyloid beta -peptide (A beta) and induces significant aggregation of the peptide. In addition to the A beta aggregation, the redox activity of the Fe(III) ion bound to A beta is considered to play a role in the pathogenesis of Alzheimer's disease. In order to understand the role of Fe(III) in A beta aggregation and neurotoxicity, we have examined the Fe(IH)-binding mode of human A beta by Raman spectroscopy. The Raman spectra of Fe(III)-A beta complexes excited at 514.5 nm are dominated by resonance Raman bands of metal-bound tyrosinate, evidencing that the Fe(III) ion primarily binds to A beta via the phenolic oxygen of Tyr10. In addition, carboxylate groups of glutamate/aspartate side chains are also bound to Fe(III). On the other hand, histidine residues in the N-terminal hydrophilic region of A beta do not bind to Fe(III), These results are in sharp contrast to the Zn(II)- or Cu(II)-induced aggregation of A beta, in which histidine residues act as the primary metal binding sites. The Fe(III)Tyr10 binding may play an important role in A beta aggregation and in decreasing the reduction potential of the bound Fe(III) ion. (C) 2001 Elsevier Science B.V. All rights reserved.