Atomic-resolution three-dimensional structure of amyloid β fibrils bearing the Osaka mutation

Angew Chem Int Ed Engl. 2015 Jan 2;54(1):331-5. doi: 10.1002/anie.201408598. Epub 2014 Nov 13.

Abstract

Despite its central importance for understanding the molecular basis of Alzheimer's disease (AD), high-resolution structural information on amyloid β-peptide (Aβ) fibrils, which are intimately linked with AD, is scarce. We report an atomic-resolution fibril structure of the Aβ1-40 peptide with the Osaka mutation (E22Δ), associated with early-onset AD. The structure, which differs substantially from all previously proposed models, is based on a large number of unambiguous intra- and intermolecular solid-state NMR distance restraints.

Keywords: Alzheimer's disease; amyloids; solid-state NMR spectroscopy; structure elucidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / genetics*
  • Amyloid beta-Peptides / ultrastructure*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics*
  • Peptide Fragments / ultrastructure*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-40)