Molecular alignment within beta-sheets in Abeta(14-23) fibrils: solid-state NMR experiments and theoretical predictions.
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.
Bu
Zimei
Z
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Shi
Yuan
Y
Callaway
David J E
DJ
Tycko
Robert
R
D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000682:Amyloid