Site-specific identification of non-beta-strand conformations in Alzheimer's beta-amyloid fibrils by solid-state NMR.
The most well-established structural feature of amyloid fibrils is the cross-beta motif, an extended beta-sheet structure formed by beta-strands oriented perpendicular to the long fibril axis. Direct experimental identification of non-beta-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 beta-amyloid peptide associated with Alzheimer's disease (Abeta(1-40)), prepared synthetically with pairs of (13)C labels at consecutive backbone carbonyl sites. The measurements probe the peptide backbone conformation in residues 24-30, a segment where a non-beta-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 phi and psi backbone torsion angles between the labeled carbonyl sites, indicate non-beta-strand conformations at G25, S26, and G29. These results represent the first site-specific identification and characterization of non-beta-strand peptide conformations in an amyloid fibril.
Antzutkin
Oleg N
ON
Department of Inorganic Chemistry, Luleå University of Technology, Luleå, Sweden.
Balbach
John J
JJ
Tycko
Robert
R
D000544:Alzheimer Disease / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D002247:Carbon Isotopes; D003198:Computer Simulation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D002247:Carbon Isotopes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)