Site-Specific Identification of Non-ß-Strand Conformations in Alzheimer's ß-Amyloid Fibrils by Solid-State NMR

• Published in: Biophysical journal 2003, Vol.84 (5), p.3326
• Main Authors: Antzutkin, Oleg, Balbach, John J., Tycko, Robert
• Format: Article
• Language: English
• Subjects: Chemistry of Interfaces; Gränsytors kemi
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(03)70057-5

The most well-established structural feature of amyloid fibrils is the cross-ß motif, an extended ß-sheet structure formed by ß-strands oriented perpendicular to the long fibril axis. Direct experimental identification of non-ß-strand conformations in amyloid fibrils has not been reported previously. Here we report the results of solid-state NMR measurements on amyloid fibrils formed by the 40-residue ß-amyloid peptide associated with Alzheimer's disease (Aß1-40), prepared synthetically with pairs of 13C labels at consecutive backbone carbonyl sites. The measurements probe the peptide backbone conformation in residues 24-30, a segment where a non-ß-strand conformation has been suggested by earlier sequence analysis, cross-linking experiments, and molecular modeling. Data obtained with the fpRFDR-CT, DQCSA, and 2D MAS exchange solid-state NMR techniques, which provide independent constraints on the and backbone torsion angles between the labeled carbonyl sites, indicate non-ß-strand conformations at G25, S26, and G29. These results represent the first site-specific identification and characterization of non-ß-strand peptide conformations in an amyloid fibril