Spectroscopic Characterization of Intermolecular Interaction of Amyloid β Promoted on GM1 Micelles.
Spectroscopic Characterization of Intermolecular Interaction of Amyloid β Promoted on GM1 Micelles.
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DOI：
10.4061/2011/925073
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发表时间：
2010-12-28
影响因子：
--
通讯作者：
Kato K
中科院分区：
文献类型：
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作者：
Yagi-Utsumi M;Matsuo K;Yanagisawa K;Gekko K;Kato K
GM 1神经节苷脂簇作为单体非结构化淀粉样蛋白β（Aβ）构象转变为其毒性β结构聚集体的平台。 我们先前已经证明，在神经节苷脂过量的条件下，容纳在lyso-GM 1或GM 1胶束的疏水/亲水界面上的Aβ（1-40）呈现α-螺旋结构。 为了更好地理解GM 1簇上Aβ α-到-β构象转变的潜在机制，我们用GM 1滴定Aβ（1-40）进行光谱表征。 研究表明，在GM 1胶束上Aβ（1 - 40）密度较高的条件下，Aβ（1 - 40）中更多地存在硫磺素T-（ThT-）反应性β结构。 在这种情况下，C端疏水性锚Val 39-Val 40显示出与ThT反应的两种不同的构象状态，而这种Aβ物质不是由较小的lyso-GM 1胶束产生的。 这些发现表明，GM 1簇通过其C-末端促进特异性Aβ-Aβ相互作用，并根据簇的大小和曲率形成ThT反应性β结构。
Clusters of GM1 gangliosides act as platforms for conformational transition of monomeric, unstructured amyloid β (Aβ) to its toxic β-structured aggregates. We have previously shown that Aβ(1–40) accommodated on the hydrophobic/hydrophilic interface of lyso-GM1 or GM1 micelles assumes α-helical structures under ganglioside-excess conditions. For better understanding of the mechanisms underlying the α-to-β conformational transition of Aβ on GM1 clusters, we performed spectroscopic characterization of Aβ(1–40) titrated with GM1. It was revealed that the thioflavin T- (ThT-) reactive β-structure is more populated in Aβ(1–40) under conditions where the Aβ(1–40) density on GM1 micelles is high. Under this circumstance, the C-terminal hydrophobic anchor Val39-Val40 shows two distinct conformational states that are reactive with ThT, while such Aβ species were not generated by smaller lyso-GM1 micelles. These findings suggest that GM1 clusters promote specific Aβ-Aβ interactions through their C-termini coupled with formation of the ThT-reactive β-structure depending on sizes and curvatures of the clusters.