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.
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.
Emilie
E
Cerf
Rabia
R
Sarroukh
Shiori
S
Tamamizu-Kato
Leonid
L
Breydo
Sylvie
S
Derclaye
Yves F
YF
Dufrêne
Vasanthy
V
Narayanaswami
Erik
E
Goormaghtigh
Jean-Marie
JM
Ruysschaert
Vincent
V
Raussens
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)