Antiparallel beta-sheet: a signature structure of the oligomeric amyloid beta-peptide.
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.
Cerf
Emilie
E
Center for Structural Biology and Bioinformatics, Laboratory for Structure and Function of Biological Membranes, Faculté des Sciences, Université Libre de Bruxelles, CP 206/2, Blvd. du Triomphe, B-1050 Brussels, Belgium.
Sarroukh
Rabia
R
Tamamizu-Kato
Shiori
S
Breydo
Leonid
L
Derclaye
Sylvie
S
Dufrêne
Yves F
YF
Narayanaswami
Vasanthy
V
Goormaghtigh
Erik
E
Ruysschaert
Jean-Marie
JM
Raussens
Vincent
V
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)