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    Biophys J. 2007 Jan 15;92(2):594-602. Epub 2006 Oct 20.

    Molecular alignment within beta-sheets in Abeta(14-23) fibrils: solid-state NMR experiments and theoretical predictions.

    Source

    Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

    Abstract

    We report investigations of the molecular structure of amyloid fibrils formed by residues 14-23 of the beta-amyloid peptide associated with Alzheimer's disease (Abeta(14-23)), using solid-state nuclear magnetic resonance (NMR) techniques in conjunction with electron microscopy and atomic force microscopy. The NMR measurements, which include two-dimensional proton-mediated (13)C-(13)C exchange and two-dimensional relayed proton-mediated (13)C-(13)C exchange spectra, show that Abeta(14-23) fibrils contain antiparallel beta-sheets with a registry of backbone hydrogen bonds that aligns residue 17+k of each peptide molecule with residue 22-k of neighboring molecules in the same beta-sheet. We compare these results, as well as previously reported experimental results for fibrils formed by other beta-amyloid fragments, with theoretical predictions of molecular alignment based on databases of residue-specific alignments in antiparallel beta-sheets in known protein structures. While the theoretical predictions are not in exact agreement with the experimental results, they facilitate the design of experiments by suggesting a small number of plausible alignments that are readily distinguished by solid-state NMR.

    PMID:
    17056725
    [PubMed - indexed for MEDLINE]
    PMCID: PMC1751388
    Free PMC Article

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