Mass Spectral Studies Reveal the Structure of Aβ1–16–Cu²⁺ Complex Resembling ATCUN Motif

In Alzheimer’s disease, copper binds to amyloid beta (Aβ) peptide and generates oxidative stress. The coordination of histidine (His) residues to Cu²⁺ is still uncertain. We studied Cu²⁺ binding to Aβ1–16 peptide using the diethyl pyrocarbonate (DEPC) assay and mass spectrometry. Our results show that only one His is involved in Cu²⁺ coordination, which is identified as His6 using mass spectral studies. Novel nickel displacement studies have further supported the proposal that the Cu²⁺ binding site of Aβ1–16 peptide resembles the ATCUN motif of human serum albumin.