Alanine-2 Carbonyl is an Oxygen Ligand in Cu2 Coordination of Alzheimer's Disease Amyloid-beta Peptide - Relevance to N-Terminally Truncated Forms

Abstract

Copper interactions with the beta-amyloid peptide (Abeta) are believed to play a role in Alzheimer's disease (AD), in particular due to production of reactive oxygen species and Cu(2+)-mediated oligomerization. To understand the role that copper might play in these processes, a detailed knowledge of the fundamental Cu(2+)/Abeta interactions is essential. To date, the identity of the oxygen ligand(s) involved in Cu(2+) coordination by Abeta has remained unclear. Here, we have used site-specific (13)C and (15)N 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 Cu(..