Lopez del Amo Juan Miguel, Fink Uwe, Dasari Muralidhar, Grelle Gerlinde, Wanker Erich E, Bieschke Jan, Reif Bernd
Helmholtz-Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
J Mol Biol. 2012 Aug 24;421(4-5):517-24. doi: 10.1016/j.jmb.2012.01.013. Epub 2012 Jan 28.
The green tea compound epigallocatechin-3-gallate (EGCG) inhibits Alzheimer's disease β-amyloid peptide (Aβ) neurotoxicity. Solution-state NMR allows probing initial EGCG-Aβ interactions. We show that EGCG-induced Aβ oligomers adopt a well-defined structure and are amenable for magic angle spinning solid-state NMR investigations. We find that EGCG interferes with the aromatic hydrophobic core of Aβ. The C-terminal part of the Aβ peptide (residues 22-39) adopts a β-sheet conformation, whereas the N-terminus (residues 1-20) is unstructured. The characteristic salt bridge involving residues D23 and K28 is present in the structure of these oligomeric Aβ aggregates as well. The structural analysis of small-molecule-induced amyloid aggregates will open new perspectives for Alzheimer's disease drug development.
绿茶成分表没食子儿茶素没食子酸酯（EGCG）可抑制阿尔茨海默病β-淀粉样肽（Aβ）的神经毒性。溶液态核磁共振可用于探究EGCG与Aβ的初始相互作用。我们发现，EGCG诱导形成的Aβ寡聚体具有明确的结构，适用于魔角旋转固态核磁共振研究。我们发现EGCG会干扰Aβ的芳香疏水核心。Aβ肽的C末端部分（第22 - 39位氨基酸残基）呈β-折叠构象，而N末端（第1 - 20位氨基酸残基）则无特定结构。这些寡聚Aβ聚集体的结构中也存在由第23位天冬氨酸（D23）和第28位赖氨酸（K28）形成的特征性盐桥。小分子诱导淀粉样聚集体的结构分析将为阿尔茨海默病药物研发开辟新的前景。
