Formation of GM1 Ganglioside Clusters on the Lipid Membrane Containing Sphingomyeline and Cholesterol

Formation of GM1 Ganglioside Clusters on the Lipid Membrane Containing Sphingomyeline and Cholesterol
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DOI:
10.1021/jp207881k
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发表时间:
2012-05-03
影响因子:
3.3
通讯作者:
Hoshino, Tyuji
Hoshino, Tyuji
中科院分区:
化学3区
文献类型:
--
作者:
Mori, Kenichi;Mahmood, Md. Iqbal;Hoshino, Tyuji

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GM 1神经节苷脂与鞘磷脂(SM)和胆固醇(Chol)形成微结构域,并深入参与淀粉样β(A β)肽在神经膜上的聚集。我们对两种含GM 1神经节苷脂的脂双层:GM 1/SM/Chol和GM 1/POPC进行了分子动力学模拟。10和100作为模拟以及具有不同初始脂质排列的另一组10 ns模拟基本上显示出相同的计算结果。GM 1/SM/Chol膜中的GM 1分子聚集,而GM 1/POPC膜中的GM 1分子分散。也就是说,仅在GM 1/SM/Chol混合膜上观察到GM 1簇的形成。由于缩合,GM 1簇的聚糖部分之间出现许多氢键。通过比较两种膜中脂质分子的分布,发现胆固醇在防止膜交错和稳定其他脂质分子相互作用方面具有重要作用。胆固醇的这种性质促进了GM 1簇的形成。
GM1 gangliosides form a microdomain with sphingomyeline (SM) and cholesterol (Chol) and are deeply involved in the aggregation of amyloid beta (A beta) peptides on neural membranes. We performed molecular dynamics simulations on two kinds of lipid bilayers containing GM1 ganglioside: GM1/SM/Chol and GM1/POPC. Both 10 and 100 as simulations and another set of 10 ns simulations with different initial lipid arrangement essentially showed the same computational results. GM1 molecules in the GM1/SM/Chol membrane were condensed, whereas those in GM1/POPC membrane scattered. That is, the formation of GM1 cluster was observed only on the GM1/SM/Chol mixed membrane. There appeared numerous hydrogen bonds among glycan portions of the GM1 clusters due to the condensation. A comparison in distribution of lipid molecules between the two kinds of membranes suggested that cholesterol had important roles to prevent the membrane from interdigitation and to stabilize other lipids for interacting with each other. This property of cholesterol promotes the formation of GM1 clusters.