Absolute structural constraints on amyloid fibrils from solid-state NMR spectroscopy of partially oriented samples.
We demonstrate that absolute, molecular-level structural information can be obtained from solid-state NMR measurements on partially oriented amyloid fibrils. Specifically, we show that the direction of the fibril axis relative to a carbonyl 13C chemical shift anisotropy (CSA) tensor can be determined from magic-angle spinning (MAS) sideband patterns in 13C NMR spectra of fibrils deposited on planar substrates. Deposition of fibrils on a planar substrate creates a highly anisotropic distribution of fibril orientations (hence, CSA tensor orientations) with most fibrils lying in the substrate plane. The anisotropic orientational distribution gives rise to distorted spinning sideband patterns in MAS spectra from which the fibril axis direction can be inferred. The experimentally determined fibril axis direction relative to the carbonyl CSA tensor of Val12 in fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (Abeta1-40) agrees well with the predictions of a recent structural model (Petkova et al. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 16742-16747) in which Val12 is contained in a parallel beta-sheet in the cross-beta motif characteristic of amyloid fibrils.
Oyler
Nathan A
NA
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 112, Bethesda, Maryland 20892-0520, USA.
Tycko
Robert
R
D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D002247:Carbon Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation
D000682:Amyloid; D016229:Amyloid beta-Peptides; D002247:Carbon Isotopes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)