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Article
Nature Structural Biology  2, 990 - 998 (1995)
doi:10.1038/nsb1195-990

Structural model for the bold beta-amyloid fibril based on interstrand alignment of an antiparallel-sheet comprising a C-terminal peptide

Peter T. Lansbury Jr.1, Philip R. Costa1, 2, Janet M. Griffiths1, 2, 4, Eric J. Simon3, 5, Michèle Auger1, 2, 6, Kurt J. Halverson1, 7, David A. Kocisko1, Zachary S. Hendsch1, 3, Ted T. Ashburn1, Richard G.S. Spencer1, 2, 8, Bruce Tidor1, 3 & Robert G. Griffin1, 2

  1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

  2Francis Bitter National Magnet Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

  3Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

  4present address: Department of Chemical Engineering, Massachusetts Institute of Technology, Harvard University, Cambridge, Massachusetts, USA

  5present address: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA

  6present address: Laval University, Quebec City, Quebec, Canada

  7present address: 3M Corp., St. Paul, Minnesota USA

  8current address: National Institute on Aging, Baltimore, Maryland, USA

Amyloids are a class of noncrystalline, yet ordered, protein aggregates. A new approach was used to provide the initial structural data on an amyloid fibril—comprising a peptide (beta34−42) from the C-terminus of the beta-amyloid protein—based on measurement of intramolecular 13C−13C distances and 13C chemical shifts by solid-state 13C NMR and individual amide absorption frequencies by isotope-edited infrared spectroscopy. Intermolecular orientation and alignment within the amyloid sheet was determined by fitting models to observed intermolecular 13C−13C couplings. Although the structural model we present is defined to relatively low resolution, it nevertheless shows a pleated antiparallel beta-sheet characterized by a specific intermolecular alignment.

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