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

Anne K Schütz (1, 2) , Toni Vagt , Matthias Huber (3) , Oxana y Ovchinnikova , Riccardo Cadalbert , Joseph Wall , Peter Güntert (4, 5) , Anja Böckmann (6) , Rudi Glockshuber , Beat H Meier

1 OCA - Observatoire de la Côte d'Azur
2 LAGRANGE - Joseph Louis LAGRANGE
3 EPFL - Ecole Polytechnique Fédérale de Lausanne
4 Center for Biomolecular Magnetic Resonance
5 Institute of Biophysical Chemistry and Frankfurt Institute for Advanced Studies
6 IBCP - Institut de biologie et chimie des protéines [Lyon]

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.

Domains: Life Sciences [q-bio]

Anne K Schütz, Toni Vagt, Matthias Huber, Oxana y Ovchinnikova, Riccardo Cadalbert, et al.. Atomic-resolution three-dimensional structure of amyloid β fibrils bearing the Osaka mutation.. Angewandte Chemie International Edition, 2015, 54 (1), pp.331-5. ⟨hal-01147011⟩