Modeling Membrane Deformations and Lipid Demixing upon Protein-Membrane Interaction: The BAR Dimer Adsorption
Modeling Membrane Deformations and Lipid Demixing upon Protein-Membrane Interaction: The BAR Dimer Adsorption
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DOI：
10.1016/j.bpj.2009.07.006
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发表时间：
2009-09-16
影响因子：
3.4
通讯作者：
Weinstein, Harel
中科院分区：
文献类型：
--
作者：
Khelashvili, George;Harries, Daniel;Weinstein, Harel
我们使用自一致的平均场理论，旨在研究与蛋白质相互作用时的膜重塑和脂质分解，探索BAR结构域与异质成分的大斑块脂质膜相互作用。计算模型包括静电相互作用和膜的弹性能对系统自由能的贡献，以及盐和脂质的混合熵。我们的模拟结果表明，单吸附Amphiphysin BAR二聚体能够稳定明显弯曲的膜。然而，我们预测这种变形只会发生在具有高曲率固有倾向的膜斑块上，这反映在倾向于产生与BAR晚餐本身曲率密切匹配的局部扭曲上。BAR-膜相互作用的这种有利的预处理可能是相互作用引起的局部脂质脱混等扰动的结果，或者是BAR结构域的两相n -螺旋的预先插入。从我们的模拟来看，在BAR二聚体的影响下，带电脂质的局部分离不能在双层小叶之间产生足够高的不对称性来诱导显著的弯曲。在缺乏有利于膜不对称的额外能量贡献的情况下，相对于热波动预期的波动，膜在单BAR二聚体吸附时将保持几乎平坦。因此，我们得出结论，n -螺旋插入在膜的局部扰动和弯曲中具有关键的机制作用，然后通过与BAR二聚体的静电相互作用稳定。我们讨论了如何使用这些结果来估计在空间非各向同性自发曲率方面的BARs弯曲膜的趋势。
We use a self-consistent mean-field theory, designed to investigate membrane reshaping and lipid demixing upon interaction with proteins, to explore BAR domains interacting with large patches of lipid membranes of heterogeneous compositions. The computational model includes contributions to the system free energy from electrostatic interactions and elastic energies of the membrane, as well as salt and lipid mixing entropies. The results from our simulation of a single adsorbing Amphiphysin BAR dimer indicate that it is capable of stabilizing a significantly curved membrane. However, we predict that such deformations will occur only for membrane patches that have the inherent propensity for high curvature, reflected in the tendency to create local distortions that closely match the curvature of the BAR dinner itself. Such favorable preconditioning for BAR-membrane interaction may be the result of perturbations such as local lipid demixing induced by the interaction, or of a prior insertion of the BAR domain's amphiphatic N-helix. From our simulations it appears that local segregation of charged lipids under the influence of the BAR dimer cannot produce high enough asymmetry between bilayer leaflets to induce significant bending. In the absence of additional energy contributions that favor membrane asymmetry, the membrane will remain nearly flat upon single BAR dimer adsorption, relative to the undulation expected from thermal fluctuations. Thus, we conclude that the N-helix insertions have a critical mechanistic role in the local perturbation and curving of the membrane, which is then stabilized by the electrostatic interaction with the BAR dimer. We discuss how these results can be used to estimate the tendency of BARs to bend membranes in terms of a spatially nonisotropic spontaneous curvature.