Verification of the Intermolecular Parallel β-Sheet in E22K-Aβ42 Aggregates by Solid-State NMR Using Rotational Resonance : Implications for the Supramolecular Arrangement of the Toxic Conformer of Aβ42

概要

論文の詳細を見る
Formation of the intermolecular β-sheet is a key event in the aggregation of 42-residue amyloid-β (Aβ42). We have recently identified a physiological and toxic conformer, the turn positions of which are slightly different from each other, in the aggregates of E22K-Aβ42 (one of the mutants related to cerebral amyloid angiopathy). However, it remains unclear whether the intermolecular β-sheet in the E22K-Aβ42 aggregates is parallel or antiparallel. We prepared an equal mixture of E22K-Aβ42 aggregates labeled at Cα and those labeled at C=O with 13C, whose intermolecular 13C–13C distance was estimated by solid-state NMR using rotational resonance (R2). The intermolecular proximity of β-strands at positions 21 and 30 was less than 6 Å, supporting the existence of the intermolecular parallel β-sheet in the E22K-Aβ42 aggregates as well as in wild-type Aβ42 aggregates. The results also suggest that each conformer would not accumulate alternately, but form a relatively large assembly.
社団法人日本農芸化学会の論文
2008-08-23