Antiparallel beta-sheet: a signature structure of the oligomeric amyloid beta-peptide

• Published in: Biochemical journal Vol. 421; no. 3; p. 415
• Main Authors: Cerf, Emilie, Sarroukh, Rabia, Tamamizu-Kato, Shiori, Breydo, Leonid, Derclaye, Sylvie, Dufrêne, Yves F, Narayanaswami, Vasanthy, Goormaghtigh, Erik, Ruysschaert, Jean-Marie, Raussens, Vincent
• Format: Journal Article
• Language: English
• Published: England 01-08-2009
• Subjects: Alzheimer Disease - metabolism; Amino Acid Sequence; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Humans; Molecular Sequence Data; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Protein Folding; Protein Structure, Secondary; Spectroscopy, Fourier Transform Infrared
• ISSN: 1470-8728
• DOI: 10.1042/BJ20090379

AD (Alzheimer's disease) is linked to Abeta (amyloid beta-peptide) misfolding. Studies demonstrate that the level of soluble Abeta oligomeric forms correlates better with the progression of the disease than the level of fibrillar forms. Conformation-dependent antibodies have been developed to detect either Abeta oligomers or fibrils, suggesting that structural differences between these forms of Abeta exist. Using conditions which yield well-defined Abeta-(1-42) oligomers or fibrils, we studied the secondary structure of these species by ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy. Whereas fibrillar Abeta was organized in a parallel beta-sheet conformation, oligomeric Abeta displayed distinct spectral features, which were attributed to an antiparallel beta-sheet structure. We also noted striking similarities between Abeta oligomers spectra and those of bacterial outer membrane porins. We discuss our results in terms of a possible organization of the antiparallel beta-sheets in Abeta oligomers, which may be related to reported effects of these highly toxic species in the amyloid pathogenesis associated with AD.