Supramolecular structure in full-length Alzheimer's β-amyloid fibrils: Evidence for a parallel β-sheet organization from solid-state nuclear magnetic resonance

Abstract

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 radiofrequencydriven 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.