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

Abstract

The Fe(III) ion binds to amyloid β-peptide (Aβ) and induces significant aggregation of the peptide. In addition to the Aβ aggregation, the redox activity of the Fe(III) ion bound to Aβ is considered to play a role in the pathogenesis of Alzheimer's disease. In order to understand the role of Fe(III) in Aβ aggregation and neurotoxicity, we have examined the Fe(III)-binding mode of human Aβ by Raman spectroscopy. The Raman spectra of Fe(III)–Aβ 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 Aβ 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 Aβ do not bind to Fe(III). These results are in sharp contrast to the Zn(II)- or Cu(II)-induced aggregation of Aβ, in which histidine residues act as the primary metal binding sites. The Fe(III)–Tyr10 binding may play an important role in Aβ aggregation and in decreasing the reduction potential of the bound Fe(III) ion.