Characterization of Aβ aggregation mechanism probed by congo red.
β-Amyloid peptide (1) (Aβ) aggregates are toxic to neuron and the main cause of Alzheimer's disease (AD). The role of congo red (CR) on Aβ aggregation is controversial in aqueous solution. Both prevention and promotion of Aβ aggregation have been proposed, suggesting that CR may interact with Aβ of different structural conformations resulting in different effects on Aβ aggregation behavior. CR with these characteristics can be applied to probe the molecular mechanism of Aβ aggregation. Therefore, in the present study, we used CR as a probe to study the Aβ aggregation behavior in sodium dodecyl sulfate (SDS) condition. Our results show that Aβ(40) adopts two short helices at Q15-S26 and K28-L34 in the SDS environment. CR can interact with the helical form of Aβ(40), and the main interaction site is located at the first helical and hydrophobic core region, residues 17-25, which is assigned as a discordant helix region. Furthermore, CR may prevent Aβ(40) undergoing α-helix to β-strand conversion, and therefore aggregation through stabilizing the helical conformation of discordant helix in SDS environment, suggesting that the discordant helix plays a key role on the conformational stabilization of Aβ. Our present study implies that any factors or molecules that can stabilize the discordant helical conformation may also prevent the Aβ aggregation in membrane associated state. This leads to a new therapeutic strategy for the development of lead compounds to AD.
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, ROC.
Chih-Ching
CC
Wang
Hsien-bin
HB
Huang
Huey-Jen
HJ
Tsay
Ming-Shi
MS
Shiao
Wen-Jin Winston
WJ
Wu
Yi-Chen
YC
Cheng
Ta-Hsien
TH
Lin
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003224:Congo Red / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D003224:Congo Red