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Biomolecular NMR Assignments

, Volume 9, Issue 1, pp 7–14 | Cite as

Solid-state NMR sequential assignment of Osaka-mutant amyloid-beta (Aβ1−40 E22Δ) fibrils

  • Matthias Huber
  • Oxana Yu. Ovchinnikova
  • Anne K. Schütz
  • Rudi GlockshuberEmail author
  • Beat H. MeierEmail author
  • Anja BöckmannEmail author
Article

Abstract

Alzheimer’s disease (AD) is the most common form of dementia. Aggregation of amyloid β (Aβ), a peptide of 39−43 residues length, into insoluble fibrils is considered to initiate the disease. Determination of the molecular structure of Aβ fibrils is technically challenging and is a significant goal in AD research that may lead to design of effective therapeutical inhibitors of Aβ aggregation. Here, we present chemical-shift assignments for fibrils formed by highly pure recombinant Aβ1−40 with the Osaka E22Δ mutation that is found in familial AD. We show that that all regions of the peptide are rigid, including the N-terminal part often believed to be flexible in Aβ wt.

Keywords

Alzheimer’s disease Solid-state NMR spectroscopy Amyloid beta Amyloid structures Fibrils 

Notes

Acknowledgments

We would like to thank Andreas Hunkeler for technical support and Hiang Dreher-Teo for providing TEV protease. This work was supported by the Agence Nationale de la Recherche (ANR-12-BS08-0013-01), the ETH Zurich, the Swiss National Science Foundation (Grants 200020_124611, 200020_146757) and the NCCR program “Neural Plasticity and Repair” and the Centre National de la Recherche Scientifique. We also acknowledge support from the European Commission under the Seventh Framework Programme (FP7), contract Bio-NMR 261863.

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Laboratory of Physical ChemistryETH ZurichZurichSwitzerland
  2. 2.Institute of Molecular Biology and BiophysicsETH ZurichZurichSwitzerland
  3. 3.Institut de Biologie et Chimie des ProtéinesUMR 5086 CNRS/Université de Lyon 1LyonFrance

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