N- and O-methylation of sphingomyelin markedly affects its membrane properties and interactions with cholesterol
N- and O-methylation of sphingomyelin markedly affects its membrane properties and interactions with cholesterol
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DOI：
10.1016/j.bbamem.2011.01.009
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发表时间：
2011-04-01
影响因子：
3.4
通讯作者：
Slotte, J. Peter
中科院分区：
文献类型：
--
作者：
Bjorkbom, Anders;Rog, Tomasz;Slotte, J. Peter
我们制备了棕榈酰鞘磷脂（PSM）类似物，其中2-NH甲基化为NMe，3-OH甲基化为OMe，或两者同时甲基化。该研究的目的是确定如何在膜界面区域的分子的这种修改影响双层膜中的interlipid相互作用。测量从SM类似物制备的囊泡膜中的DPH各向异性，我们观察到甲基化降低了凝胶相稳定性，增加了流体相紊乱，与PSM相比。2-NH的甲基化对凝胶相不稳定性的影响最大（T-m降低了约7 ℃）。原子分子动力学模拟表明，与甲基化的SM类似物的流体相双层更扩大，但薄的PSM双层相比。进一步揭示，3-OH甲基化也显著减弱了通过酰胺氮的氢键，而2-NH甲基化没有类似地影响通过3-OH的氢键。甾醇与甲基化SM类似物的相互作用受到显着影响。3-OH甲基化几乎完全消除了SM类似物形成富含甾醇的有序结构域的能力，而2-NH甲基化的SM类似物形成富含甾醇的结构域，但这些结构域比PSM形成的结构域热稳定性差（因此有序性差）。胆甾三烯醇对含有甲基化SM类似物的双层的亲和力与其对含有PSM的双层的亲和力相比也显著降低。分子动力学模拟进一步揭示，胆固醇的双层位置是更深的PSM双层相比，在由甲基化SM类似物制成的双层的位置。这项研究表明，SMs的界面性质是非常重要的脂质间的相互作用和形成的横向有序域在复杂的双层。(C)2011 Elsevier B. V.保留所有权利。
We have prepared palmitoyl sphingomyelin (PSM) analogs in which either the 2-NH was methylated to NMe, the 3-OH was methylated to OMe, or both were methylated simultaneously. The aim of the study was to determine how such modifications in the membrane interfacial region of the molecules affected interlipid interactions in bilayer membranes. Measuring DPH anisotropy in vesicle membranes prepared from the SM analogs, we observed that methylation decreased gel-phase stability and increased fluid phase disorder, when compared to PSM. Methylation of the 2-NH had the largest effect on gel-phase instability (T-m, was lowered by similar to 7 degrees C). Atomistic molecular dynamics simulations showed that fluid phase bilayers with methylated SM analogs were more expanded but thinner compared to PSM bilayers. It was further revealed that 3-OH methylation dramatically attenuated hydrogen bonding also via the amide nitrogen, whereas 2-NH methylation did not similarly affect hydrogen bonding via the 3-OH. The interactions of sterols with the methylated SM analogs were markedly affected. 3-OH methylation almost completely eliminated the capacity of the SM analog to form sterol-enriched ordered domains, whereas the 2-NH methylated SM analog formed sterol-enriched domains but these were less thermostable (and thus less ordered) than the domains formed by PSM. Cholestatrienol affinity to bilayers containing methylated SM analogs was also markedly reduced as compared to its affinity for bilayers containing PSM. Molecular dynamics simulations revealed further that cholesterol's bilayer location was deeper in PSM bilayers as compared to the location in bilayers made from methylated SM analogs. This study shows that the interfacial properties of SMs are very important for interlipid interactions and the formation of laterally ordered domains in complex bilayers. (C) 2011 Elsevier B.V. All rights reserved.