Structural and dynamic views of GM1 ganglioside.

Structural and dynamic views of GM1 ganglioside.
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GM1 神经节苷脂的结构和动态视图。

DOI:
10.1007/s10719-015-9587-5
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发表时间:
2015
期刊:
Glycoconj J
影响因子:
--
通讯作者:
Kato K.
Kato K.
中科院分区:
--
文献类型:
--
作者:
Yagi-Utsumi M;Kato K.

文献摘要

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神经节苷脂GM1主要通过在细胞表面形成GM1簇来调节多种生理和病理过程。因此,为了更好地理解簇偶联的功能促进作用,有必要详细表征GM1的糖链部分的构象性质以及这种糖鞘糖脂在膜环境中的结构和相互作用。核磁共振波谱提供了GM1在溶液和膜状环境中的构象信息。最近,先进的顺磁辅助核磁共振方法与分子动力学模拟相结合,使得定量探索包括GM1在内的一系列神经节苷脂的构象空间成为可能,并考虑到它们的微小构象。核磁共振技术也被成功地应用于研究GM1簇与淀粉样蛋白的动态相互作用,如与神经退行性疾病相关的淀粉样蛋白β和α-突触核蛋白。实验和计算方法的进一步结合将开辟新的可能性,以提供更复杂的不同系统的结构视图,例如涉及GM1的微域。
The ganglioside GM1 mediates various physiological and pathological processes mainly through the formation of GM1 clusters on cell surfaces. Therefore, detailed characterization of conformational properties of the glycan moiety of GM1 and the structures and interactions of this glycosphingolipid in membrane environments is necessary for better understanding of the clustering-coupled functional promotion. Nuclear magnetic resonance (NMR) spectroscopy has provided conformational information of GM1 in solution as well as in membrane-like environments. Recently, sophisticated paramagnetism-assisted NMR approaches combined with molecular dynamics simulations have enabled the quantitative exploration of conformational spaces of a series of gangliosides, including GM1, taking into account their minor conformations. NMR techniques have also been successfully applied to investigations of the dynamic interactions of GM1 clusters with amyloidogenic proteins such as amyloid β and α-synuclein associated with neurodegenerative disorders. Further integration of experimental and computational approaches will open up new possibilities to provide structural views of the more complicated heterogeneous systems exemplified by microdomains involving GM1.