Supramolecular Structure in Full-Length Alzheimer's β-Amyloid Fibrils: Evidence for a Parallel β-Sheet Organization from Solid-State Nuclear Magnetic Resonance

• We report constraints on the supramolecular structure of amyloid fibrils formed by the 40-residue β-amyloid peptide associated with Alzheimer's disease (Aβ1–40) obtained from solid-state nuclear magnetic resonance (NMR) measurements of intermolecular dipole-dipole couplings between 13C labels at 11 carbon sites in residues 2 through 39. The measurements are carried out under magic-angle spinning conditions, using the constant-time finite-pulse radiofrequency-driven recoupling (fpRFDR-CT) technique. We also present one-dimensional 13C magic-angle spinning NMR spectra of the labeled Aβ1–40 samples. The fpRFDR-CT data reveal nearest-neighbor intermolecular distances of 4.8 ± 0.5 Å for carbon sites from residues 12 through 39, indicating a parallel alignment of neighboring peptide chains in the predominantly β-sheet structure of the amyloid fibrils. The one-dimensional NMR spectra indicate structural order at these sites. The fpRFDR-CT data and NMR spectra also indicate structural disorder in the N-terminal segment of Aβ1–40, including the first nine residues. These results place strong constraints on any molecular-level structural model for full-length β-amyloid fibrils.

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NATURVETENSKAP  -- Kemi -- Fysikalisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Physical Chemistry (hsv//eng)

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Chemistry of Interfaces

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