Amyloid fibril formation by A beta 16-22, a seven-residue fragment of the Alzheimer's beta-amyloid peptide, and structural characterization by solid state NMR

• Published in: Biochemistry (Easton) 2000-11, Vol.39 (45), p.13748-13759
• Main Authors: Balbach, J J, Ishii, Y, Antzutkin, O N, Leapman, R D, Rizzo, N W, Dyda, F, Reed, J, Tycko, R
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - ultrastructure; Birefringence; Carbon Isotopes; Humans; Models, Chemical; Models, Molecular; Nitrogen Isotopes; Nuclear Magnetic Resonance, Biomolecular - methods; Oligopeptides - chemistry; Oligopeptides - metabolism; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Peptide Fragments - ultrastructure; Protein Conformation; Protein Structure, Secondary; X-Ray Diffraction
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi0011330

The seven-residue peptide N-acetyl-Lys-Leu-Val-Phe-Phe-Ala-Glu-NH(2), called A beta(16-22) and representing residues 16-22 of the full-length beta-amyloid peptide associated with Alzheimer's disease, is shown by electron microscopy to form highly ordered fibrils upon incubation of aqueous solutions. X-ray powder diffraction and optical birefringence measurements confirm that these are amyloid fibrils. The peptide conformation and supramolecular organization in A beta(16-22) fibrils are investigated by solid state (13)C NMR measurements. Two-dimensional magic-angle spinning (2D MAS) exchange and constant-time double-quantum-filtered dipolar recoupling (CTDQFD) measurements indicate a beta-strand conformation of the peptide backbone at the central phenylalanine. One-dimensional and two-dimensional spectra of selectively and uniformly labeled samples exhibit (13)C NMR line widths of