STRUCTURAL MODEL FOR THE BETA-AMYLOID FIBRIL BASED ON INTERSTRAND ALIGNMENT OF AN ANTIPARALLEL-SHEET COMPRISING A C-TERMINAL PEPTIDE

Amyloids are a class of noncrystalline, yet ordered, protein aggregates, A new approach was used to provide the initial structural data on an amyloid fibril-comprising a peptide (beta 34-42) from the C-terminus of the beta-amyloid protein-based on measurement of intramolecular C-13-C-13 distances and C-13 chemical shifts by solid-state C-13 NMR and individual amide absorption frequencies by isotope-edited infrared spectroscopy, Intermolecular orientation and alignment within the amyloid sheet was determined by fitting models to observed intermolecular C-13-C-13 couplings. Although the structural model we present is defined to relatively low resolution, it nevertheless shows a pleated antiparallel beta-sheet characterized by a specific intermolecular alignment.