Transformation of amyloid β(1-40) oligomers into fibrils is characterized by a major change in secondary structure.
Alzheimer's disease (AD) is a neurodegenerative disorder occurring in the elderly. It is widely accepted that the amyloid beta peptide (Aβ) aggregation and especially the oligomeric states rather than fibrils are involved in AD onset. We used infrared spectroscopy to provide structural information on the entire aggregation pathway of Aβ(1-40), starting from monomeric Aβ to the end of the process, fibrils. Our structural study suggests that conversion of oligomers into fibrils results from a transition from antiparallel to parallel β-sheet. These structural changes are described in terms of H-bonding rupture/formation, β-strands reorientation and β-sheet elongation. As antiparallel β-sheet structure is also observed for other amyloidogenic proteins forming oligomers, reorganization of the β-sheet implicating a reorientation of β-strands could be a generic mechanism determining the kinetics of protein misfolding. Elucidation of the process driving aggregation, including structural transitions, could be essential in a search for therapies inhibiting aggregation or disrupting aggregates.
Sarroukh
Rabia
R
Laboratory for Structure and Function of Biological Membranes, Faculté des Sciences, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, CP 206/2, Blvd. du Triomphe 1050, Brussels, Belgium.
Cerf
Emilie
E
Derclaye
Sylvie
S
Dufrêne
Yves F
YF
Goormaghtigh
Erik
E
Ruysschaert
Jean-Marie
JM
Raussens
Vincent
V
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D015398:Signal Transduction; D013055:Spectrophotometry, Infrared
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)