Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, Japan.
FEBS Lett. 2010 Feb 19;584(4):831-6. doi: 10.1016/j.febslet.2010.01.005. Epub 2010 Jan 12.
Gangliosides are targets for a variety of pathologically relevant proteins, including amyloid beta (Abeta), an important component implicated in Alzheimer's disease (AD). To provide a structural basis for this pathogenic interaction associated with AD, we conducted NMR analyses of the Abeta interactions with gangliosides using lyso-GM1 micelles as a model system. Our NMR data revealed that the sugar-lipid interface is primarily perturbed upon binding of Abeta to the micelles, underscoring the importance of the inner part of the ganglioside cluster for accommodating Abeta in comparison with the outer carbohydrate branches that provide microbial toxin- and virus-binding sites.
神经节苷脂是多种与病理相关蛋白的靶标，包括淀粉样β肽（Abeta），它是阿尔茨海默病（AD）中重要的致病成分。为了为与 AD 相关的这种致病相互作用提供结构基础，我们使用溶酶 GM1 胶束作为模型系统，通过 NMR 分析研究了 Abeta 与神经节苷脂的相互作用。我们的 NMR 数据表明，Abeta 与胶束结合后，糖脂界面主要受到干扰，这突出表明与提供微生物毒素和病毒结合位点的外碳水化合物分支相比，神经节苷脂簇的内部对于容纳 Abeta 更为重要。
