Controlling membrane cholesterol content. A role for polyunsaturated (Docosahexaenoate) phospholipids
Controlling membrane cholesterol content. A role for polyunsaturated (Docosahexaenoate) phospholipids
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DOI：
10.1021/bi0262808
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发表时间：
2002-10-15
期刊：
影响因子：
2.9
通讯作者：
Wassall, SR
中科院分区：
文献类型：
--
作者：
Brzustowicz, MR;Cherezov, V;Wassall, SR
研究了胆固醇在1,2-二二十二碳六烯基磷脂酰胆碱（22:6 -22:6 pc）和1-硬脂酰-2-二十二碳六烯基磷脂酰胆碱（18:0-22:6PC）双分子层中的分子结构。利用低角和广角x射线衍射（XRD）测定了甾醇在。20°c在22:6-22:6PC层为11 +/- 3 mol %，而在18:0-22:6PC层为55 +/- 3 mol %。在40℃时，双多不饱和膜的溶解度上升到17 +/- 3 mol %，而在实验不确定度内，饱和多不饱和膜的溶解度没有变化。在固态H-2 NMR实验中，我们比较了[3 α -H-2(1)]胆固醇在22:6-22:6PC双分子层中的分子取向及其溶解度极限，以及在18:0-22:6PC双分子层中的分子取向与相当浓度（10 mol %）。在22:6-22:6PC范围内，甾醇的倾斜角α(0) = 24°V，在20 - 40°c范围内与温度无关。相比之下，在18:0-22:6双层中，20°c的值为α(0) = 21度+/- 1度，在40°c时增加到α(0) = 24度+/- 1度。我们将胆固醇在22:6-22:6PC膜中的低溶解度归因于刚性类固醇部分与高度无序的二十二碳六烯酸（DHA）链之间的空间不相容，这有可能促进富含DHA的膜内的横向非均质性。考虑到22:6-22:6PC是体内发现的最不饱和的磷脂，本模型膜研究为阐明固醇-脂相互作用在控制局部组成组织中的作用提供了一个参考点。我们的结果形成了一个与胆固醇调节某些神经跨膜蛋白活性的能力相一致的模型的基础。
The molecular organization of cholesterol in 1,2-didocosahexaenoylphosphatidylcholine (22: 6-22:6PC) and 1-stearoyl-2-docosahexaenoylphosphatidylcholine (18:0-22:6PC) bilayers was investigated. Using low- and wide-angle X-ray diffraction (XRD), we determined that the solubility of the sterol at. 20 degreesC was 11 +/- 3 mol % in 22:6-22:6PC vs 55 +/- 3 mol % in 18:0-22:6PC bilayers. Solubility in the dipolyunsaturated membrane rose to 17 +/- 3 mol % at 40 degreesC, while in the saturated-polyunsaturated membrane there was no change within experimental uncertainty. We compared the molecular orientation of [3alpha-H-2(1)]cholesterol incorporated into 22:6-22:6PC bilayers to its solubility limit and into 18:0-22:6PC bilayers to a comparable concentration (10 mol %) in solid-state H-2 NMR experiments. The sterol possessed a tilt angle alpha(0) = 24degrees V in 22:6-22:6PC that was independent of temperature over a range from 20 to 40 degreesC. In contrast, the value was alpha(0) = 21degrees +/- 1degrees in 18:0-22:6 bilayers at 20 degreesC and increased to alpha(0) = 24degrees +/- 1degrees at 40 degreesC. We attribute the low solubility of cholesterol in 22:6-22:6PC membranes to steric incompatibility between the rigid steroid moiety and the highly disordered docosahexaenoic acid (DHA) chain, which has the potential to promote lateral heterogeneity within DHA-rich membranes. Considering 22:6-22:6PC to be the most unsaturated phospholipid found in vivo, this model membrane study provides a point of reference for elucidating the role of sterol-lipid interactions in controlling local compositional organization. Our results form the basis for a model that is consistent with cholesterol's ability to modulate the activity of certain neural transmembrane proteins.