Verification of the C-terminal intramolecular β-sheet in Aβ42 aggregates using solid-state NMR: Implications for potent neurotoxicity through the formation of radicals

Structural analysis of 42-residue amyloid β (Aβ42) aggregates using rotational resonance in solid-state NMR verified that Cβ and/or Cγ of Met-35 and the carboxyl carbon of Ala-42 are proximal enough to form an intramolecular antiparallel β-sheet in the C-terminus. The S-oxidized radical cation at Met-35, an ultimate radical species responsible for neurotoxicity, could be stabilized by the carboxylate anion at the C-terminus, resulting in aggregation to cause long-term oxidative stress.