Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina, USA.
Biophys J. 2011 Oct 19;101(8):1930-7. doi: 10.1016/j.bpj.2011.09.015.
Lipid domain formation induced by annexin was investigated in mixtures of phosphatidylcholine (PC), phosphatidylserine (PS), and cholesterol (Chol), which were selected to mimic the inner leaflet of a eukaryotic plasma membrane. Annexins are ubiquitous and abundant cytoplasmic, peripheral proteins, which bind to membranes containing PS in the presence of calcium ions (Ca(2+)), but whose function is unknown. Prompted by indications of interplay between the presence of cholesterol in PS/PC mixtures and the binding of annexins, we used Monte Carlo simulations to investigate protein and lipid domain formation in these mixtures. The set of interaction parameters between lipids and proteins was assigned by matching experimental observables to corresponding variables in the calculations. In the case of monounsaturated phospholipids, the PS-PC and PC-Chol interactions are weakly repulsive. The interaction between protein and PS was determined based on experiments of annexin binding to PC/PS mixtures in the presence of Ca(2+). Based on the proposal that PS and cholesterol form a complex in model membranes, a favorable PS-Chol interaction was postulated. Finally, protein-protein favorable interactions were also included, which are consistent with observations of large, two-dimensional, regular arrays of annexins on membranes. Those net interactions between pairs of lipids, proteins and lipids, and between proteins are all small, of the order of the average kinetic energy. We found that annexin a5 can induce formation of large PS domains, coincident with protein domains, but only if cholesterol is present.
我们研究了 annexin 在含有磷脂酰胆碱（PC）、磷脂酰丝氨酸（PS）和胆固醇（Chol）的混合物中诱导脂质域形成的情况，这些混合物被选择来模拟真核细胞膜的内小叶。 Annexin 是普遍存在且丰富的细胞质外周蛋白，在钙离子（Ca(2+)）存在的情况下与含有 PS 的膜结合，但它们的功能尚不清楚。由于提示了 PS/PC 混合物中胆固醇的存在与 annexin 结合之间的相互作用，我们使用蒙特卡罗模拟来研究这些混合物中的蛋白质和脂质域形成。通过将实验观察结果与计算中的相应变量匹配，分配了脂质和蛋白质之间的相互作用参数集。在单不饱和磷脂的情况下，PS-PC 和 PC-Chol 相互作用是弱排斥的。根据 annexin 在 Ca(2+)存在下与 PC/PS 混合物结合的实验，确定了蛋白与 PS 之间的相互作用。基于 PS 和胆固醇在模型膜中形成复合物的假设，假设了有利的 PS-Chol 相互作用。最后，还包括了蛋白质-蛋白质有利的相互作用，这与在膜上观察到的 annexin 的大二维规则排列一致。脂质对、蛋白质和脂质对之间以及蛋白质之间的那些净相互作用都很小，处于平均动能的量级。我们发现 annexin a5 可以诱导大 PS 域的形成，与蛋白质域一致，但只有在存在胆固醇的情况下。
