Atomic-resolution three-dimensional structure of amyloid β fibrils bearing the Osaka mutation.
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.
Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zurich (Switzerland).
Anne K
AK
Schütz
Toni
T
Vagt
Matthias
M
Huber
Oxana Y
OY
Ovchinnikova
Riccardo
R
Cadalbert
Joseph
J
Wall
Peter
P
Güntert
Anja
A
Böckmann
Rudi
R
Glockshuber
Beat H
BH
Meier
D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)
Alzheimer's disease; amyloids; solid-state NMR spectroscopy; structure elucidation