Journal
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Volume 30, Issue 2, Pages 160-169Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2012.677767
Keywords
nuclear magnetic resonance; congo red; beta-amyloid peptide; discordant helix
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Funding
- National Science Council of Taiwan, ROC [NSC 96-2311-B-010-010-MY3, NSC99-2627-M-715-001, NSC100-2627-M-715-001]
- Taipei Veterans General Hospital, Taiwan, Republic of China [V96C1-022, V96S4-002]
- National Research Program for Genomic Medicine and Instrumentation Center, National Taiwan University
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beta-Amyloid peptide (A beta) aggregates are toxic to neuron and the main cause of Alzheimer's disease (AD). The role of congo red (CR) on A beta aggregation is controversial in aqueous solution. Both prevention and promotion of A beta aggregation have been proposed, suggesting that CR may interact with A beta of different structural conformations resulting in different effects on A beta aggregation behavior. CR with these characteristics can be applied to probe the molecular mechanism of A beta aggregation. Therefore, in the present study, we used CR as a probe to study the A beta aggregation behavior in sodium dodecyl sulfate (SDS) condition. Our results show that A beta(40) adopts two short helices at Q15-S26 and K28-L34 in the SDS environment. CR can interact with the helical form of A beta(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 A beta(40) undergoing alpha-helix to beta-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 A beta. Our present study implies that any factors or molecules that can stabilize the discordant helical conformation may also prevent the A beta aggregation in membrane associated state. This leads to a new therapeutic strategy for the development of lead compounds to AD.
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