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

Yuichi Masuda, Azusa Nakanishi, Ryutaro Ohashi, Kiyonori Takegoshi, Takahiko Shimizu, Takuji Shirasawa, Kazuhiro Irie

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2170-2175
Number of pages6
JournalBioscience, Biotechnology and Biochemistry
Volume72
Issue number8
DOIs
Publication statusPublished - 2008

Keywords

  • Alzheimer's disease
  • Aβ42
  • Intermolecular parallel β-sheet
  • Italian mutation
  • Solid-state NMR

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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