Modification of Lipid Bilayer Structure by Diacylglycerol: A Comparative Study of Diacylglycerol and Cholesterol.
Modification of Lipid Bilayer Structure by Diacylglycerol: A Comparative Study of Diacylglycerol and Cholesterol.
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DOI：
10.1021/ct200790q
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发表时间：
2012-02-14
影响因子：
5.5
通讯作者：
Huang, Juyang
中科院分区：
文献类型：
--
作者：
Alwarawrah, Mohammad;Dai, Jian;Huang, Juyang
甘油二酯（Diacylglycerols，DAGs）是生物膜上重要的第二信使，能激活蛋白激酶C等多种酶和受体。然而，它们与胆固醇和其他脂质的相互作用以前没有使用分子动力学（MD）模拟研究。在本研究中，我们进行了9个独立的原子分子动力学模拟，专门研究了二16：0 DAG，16：0，18：1-磷脂酰胆碱（POPC）和胆固醇之间的相互作用。尽管它们在化学结构上有很大差异，但DAG和胆固醇在POPC双层中产生一些非常相似的作用：增加酰基链顺序和双层厚度，降低单位脂质体积，并减少分子的横向扩散。更重要的是，DAG还在PC双层中产生强烈的“凝聚效应”。相比之下，胆固醇在产生上述效果方面比DAG更有效。凝聚效应的驱动力是它们的分子形状：DAG和胆固醇都有小的极性头基和大的疏水体。在脂质双层中，为了避免其疏水部分不利地暴露于水，相邻的磷脂头基向胆固醇或DAG移动以提供覆盖。因此，DAG，胆固醇和磷脂之间看似复杂的相互作用可以使用伞模型清楚地解释。我们的模拟证实了DAG增加磷脂头基之间的间距的假设，这对于激活蛋白激酶C和其他酶是重要的。有趣的是，我们的模拟还表明，传统观点认为DAG产生的间距直接位于DAG分子上方是不正确的;相反，由于伞效应，最大的间距通常发生在DAG的第一和第二最近邻PC头基之间。
Diacylglycerols (DAGs) are important second messengers in biomembranes, and they can activate protein kinase C and many other enzymes and receptors. However, their interactions with cholesterol and other lipids have not been previously studied using molecular dynamics (MD) simulation. In this study, nine independent atomistic MD simulations were performed to specifically investigate the interactions between di16:0DAG, 16:0,18:1-phosphatidylcholine (POPC), and cholesterol. Despite of their substantial differences in chemical structure, DAG and cholesterol produce some very similar effects in POPC bilayers: increasing acyl chain order and bilayer thickness, reducing volume-per-lipid, and decreasing lateral diffusion of molecules. More significantly, DAG also produces a strong “condensing effect” in PC bilayers. In comparison, cholesterol is more effective than DAG in producing the above effects. The driving force for the condensing effect is their molecular shape: DAG and cholesterol both have small polar headgroups and large hydrophobic bodies. In a lipid bilayer, in order to avoid the unfavorable exposure of their hydrophobic parts to water, neighboring phospholipid headgroups move toward cholesterol or DAG to provide cover. Thus, seemingly complex interactions between DAG, cholesterol and phospholipid can be clearly explained using the Umbrella Model. Our simulations confirmed the hypothesis that DAG increases the spacing between phospholipid headgroups, which is important for activating protein kinase C and other enzymes. Interestingly, our simulations also show that the conventional wisdom that the spacing created by a DAG is directly above the DAG molecule is incorrect; instead, the largest spacing usually occurs between the first and the second nearest-neighbor PC headgroups from a DAG, due to the umbrella effect.
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影响因子：
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