Membrane Curvature Sensing by Amphipathic Helices: Insights from Implicit Membrane Modeling
Membrane Curvature Sensing by Amphipathic Helices: Insights from Implicit Membrane Modeling
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DOI：
10.1016/j.bpj.2018.03.030
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发表时间：
2018-05-08
影响因子：
3.4
通讯作者：
Lazaridis, Themis
中科院分区：
文献类型：
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作者：
Nepal, Binod;Leveritt, John, III;Lazaridis, Themis
通过特定蛋白质结合到膜表面上介导的脂质膜曲率的感测和产生在细胞生物学中起着至关重要的作用。已经提出了一些机制，但这些过程的分子理解是不完整的。全原子分子动力学模拟提供了有价值的见解，但计算要求极高。隐式膜模拟可以提供一个可行的替代方案，但目前的模型只适用于平面膜。在这项工作中，隐式膜模型1扩展到球形和管状膜。从平面到弯曲形状的几何变化是直接的，但不足以捕获全曲率效应，包括脂质堆积的变化。在此，通过侧压力分布图考虑这些填充效应。扩展的隐式膜模型1测试的野生型和突变体的抗菌肽爪蟾抗菌肽，ALPS基序的arfgapl，α-突触核蛋白，和ENTH结构域。在这些系统中，该模型与实验定性一致。我们证实，有利的静电相互作用往往会削弱曲率灵敏度在强疏水相互作用的存在下，但实际上可能有一个积极的影响时，这些都是弱的。我们还发现，结合到囊泡是更有利的比结合到相同直径的管和α-突触核蛋白的长螺旋倾向于取向沿着轴管，而较短的螺旋倾向于取向垂直于它。通过一个特定的方向可以提供一种机制，耦合蛋白质寡聚化小管形成。
Sensing and generation of lipid membrane curvature, mediated by the binding of specific proteins onto the membrane surface, play crucial roles in cell biology. A number of mechanisms have been proposed, but the molecular understanding of these processes is incomplete. All-atom molecular dynamics simulations have offered valuable insights but are extremely demanding computationally. Implicit membrane simulations could provide a viable alternative, but current models apply only to planar membranes. In this work, the implicit membrane model 1 is extended to spherical and tubular membranes. The geometric change from planar to curved shapes is straightforward but insufficient for capturing the full curvature effect, which includes changes in lipid packing. Here, these packing effects are taken into account via the lateral pressure profile. The extended implicit membrane model 1 is tested on the wild-types and mutants of the antimicrobial peptide magainin, the ALPS motif of arfgapl, alpha-synuclein, and an ENTH domain. In these systems, the model is in qualitative agreement with experiments. We confirm that favorable electrostatic interactions tend to weaken curvature sensitivity in the presence of strong hydrophobic interactions but may actually have a positive effect when those are weak. We also find that binding to vesicles is more favorable than binding to tubes of the same diameter and that the long helix of alpha-synuclein tends to orient along the axis of tubes, whereas shorter helices tend to orient perpendicular to it. Adoption of a specific orientation could provide a mechanism for coupling protein oligomerization to tubule formation.