Alanine-2 carbonyl is an oxygen ligand in Cu2 coordination of Alzheimer's disease amyloid-β peptide - Relevance to N-terminally truncated forms

Abstract

(Graph Presented) Copper interactions with the β-amyloid peptide (Aβ) are believed to play a role in Alzheimer's disease (AD), in particular due to production of reactive oxygen species and Cu2+-mediated oligomerization. To understand the role that copper might play in these processes, a detailed knowledge of the fundamental Cu2+/Aβ interactions is essential. To date, the identity of the oxygen ligand(s) involved in Cu2+ coordination by Aβ has remained unclear. Here, we have used site-specific 13C and 15N labeling in conjunction with hyperfine sublevel correlation (HYSCORE) spectroscopy to unambiguously identify the carbonyl of Alanine-2 as an oxygen ligand in one of the pH-dependent Cu2+ co..