β-Glucosylation of cholesterol reduces sterol-sphingomyelin interactions
β-Glucosylation of cholesterol reduces sterol-sphingomyelin interactions
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胆固醇的β-葡萄糖基化减少甾醇-鞘磷脂相互作用
DOI：
10.1016/j.bbamem.2020.183496
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Hirabayashi Yoshio
中科院分区：
文献类型：
--
作者：
Hanashima Shinya;Fukuda Nanami;Malabed Raymond;Murata Michio;Kinoshita Msanao;Greimel Peter;Hirabayashi Yoshio
胆固醇-β-D-葡萄糖苷（ChoGlc）是一种哺乳动物糖脂，在脑组织中表达。研究了糖基化对胆固醇（Cho）有序化和脂质相互作用的影响，并探讨了参与这些相互作用的可能分子机制。差示扫描量热法显示，ChoGlc与SSM在类似程度的Cho混溶。固态2 H NMR的氘代SSM和荧光各向异性使用1，6-二苯基己三烯表明，葡萄糖基化的Cho显着降低的效果的甾醇四环核心的SSM链的顺序。通过固态NMR分析氘代和氟化ChoGlc类似物进一步检查甾醇核心的取向。ChoGlc有一个较小的倾斜角之间的长分子轴（C3-C17）和膜正常比Cho在SSM双层，倾斜角的波动在很大程度上不受温度依赖性的迁移率变化的SSM酰基链。ChoGlc的固醇核心的这种取向导致减少固醇-SSM相互作用。MD模拟结果表明，Glc部分扰乱SSM-甾醇相互作用，这降低了磷酸胆碱头基的保护伞效应，因为亲水性葡萄糖部分与SSM酰胺基团位于相同的深度。ChoGlc和Cho之间的这些差异也削弱了SSM-ChoGlc相互作用。因此，Cho和ChoGlc的分布和定位可能控制基于鞘磷脂的结构域的稳定性，所述结构域瞬时发生在生物膜中的特定位置。
Cholesteryl-β-D-glucoside (ChoGlc) is a mammalian glycolipid that is expressed in brain tissue. The effects of glucosylation on the ordering and lipid interactions of cholesterol (Cho) were examined in membranes composed of N-stearoyl sphingomyelin (SSM), which is abundant in the brain, and to investigate the possible molecular mechanism involved in these interactions. Differential scanning calorimetry revealed that ChoGlc was miscible with SSM in a similar extent of Cho. Solid-state2H NMR of deuterated SSM and fluorescent anisotropy using 1,6-diphenylhexatriene demonstrated that the glucosylation of Cho significantly reduced the effect of the sterol tetracyclic core on the ordering of SSM chains. The orientation of the sterol core was further examined by solid-state NMR analysis of deuterated and fluorinated ChoGlc analogues. ChoGlc had a smaller tilt angle between the long molecular axis (C3–C17) and the membrane normal than Cho in SSM bilayers, and the fluctuations in the tilt angle were largely unaffected by temperature-dependent mobility changes of SSM acyl chains. This orientation of the sterol core of ChoGlc leads to reduce sterol-SSM interactions. The MD simulation results suggested that the Glc moiety perturbs the SSM-sterol interactions, which reduces the umbrella effect of the phosphocholine headgroup because the hydrophilic glucose moiety resides at the same depth as an SSM amide group. These differences between ChoGlc and Cho also weaken the SSM-ChoGlc interactions. Thus, the distribution and localization of Cho and ChoGlc possibly control the stability of sphingomyelin-based domains that transiently occur at specific locations in biological membranes.