Bilayer-thickness-mediated interactions between integral membrane proteins
Bilayer-thickness-mediated interactions between integral membrane proteins
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DOI：
10.1103/physreve.93.042410
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发表时间：
2016-04-18
影响因子：
2.4
通讯作者：
Haselwandter, Christoph A.
中科院分区：
文献类型：
--
作者：
Kahraman, Osman;Koch, Peter D.;Haselwandter, Christoph A.
整体膜蛋白与周围脂质双分子层之间的疏水厚度失配会导致脂质双分子层厚度变形。实验和理论表明，蛋白质诱导的脂质双层厚度变形可以产生能量有利的双层介导的整体膜蛋白之间的相互作用，以及整体膜蛋白在细胞膜上大规模组织成蛋白质簇。在膜的连续弹性理论中，通过考虑双层疏水核心的压缩和膨胀、膜张力和双层弯曲，可以捕获蛋白质引起的双层厚度变形的能量成本，从而得到描述给定双层-蛋白质边界条件下脂质双层形状的双调和平衡方程。在这里，我们开发了一种结合解析和数值方法来解决与蛋白质诱导的脂质双分子层变形相关的平衡弹性方程。我们的方法可以准确预测任意蛋白质分离和相对方向上任意蛋白质对称性的厚度介导的蛋白质相互作用。我们提供了恒定和变化疏水厚度的圆柱形整体膜蛋白的精确解析解，并开发了非圆柱形蛋白质形状的微扰解析解。我们补充了这些解析解，并通过开发有限元和有限差分数值解方案来评估它们的准确性。我们提供了我们的数值解决方案的误差估计，并系统地评估了它们的收敛性。综上所述，本文提出的工作建立了一个分析和数值框架，该框架允许计算由结构生物学提出的复杂蛋白质形状的整体膜蛋白之间的双层介导的弹性相互作用，以及与活细胞提供的拥挤膜环境最相关的小蛋白质分离。
Hydrophobic thickness mismatch between integral membrane proteins and the surrounding lipid bilayer can produce lipid bilayer thickness deformations. Experiment and theory have shown that protein-induced lipid bilayer thickness deformations can yield energetically favorable bilayer-mediated interactions between integral membrane proteins, and large-scale organization of integral membrane proteins into protein clusters in cell membranes. Within the continuum elasticity theory of membranes, the energy cost of protein-induced bilayer thickness deformations can be captured by considering compression and expansion of the bilayer hydrophobic core, membrane tension, and bilayer bending, resulting in biharmonic equilibrium equations describing the shape of lipid bilayers for a given set of bilayer-protein boundary conditions. Here we develop a combined analytic and numerical methodology for the solution of the equilibrium elastic equations associated with protein-induced lipid bilayer deformations. Our methodology allows accurate prediction of thickness-mediated protein interactions for arbitrary protein symmetries at arbitrary protein separations and relative orientations. We provide exact analytic solutions for cylindrical integral membrane proteinswith constant and varying hydrophobic thickness, and develop perturbative analytic solutions for noncylindrical protein shapes. We complement these analytic solutions, and assess their accuracy, by developing both finite element and finite difference numerical solution schemes. We provide error estimates of our numerical solution schemes and systematically assess their convergence properties. Taken together, the work presented here puts into place an analytic and numerical framework which allows calculation of bilayer-mediated elastic interactions between integral membrane proteins for the complicated protein shapes suggested by structural biology and at the small protein separations most relevant for the crowded membrane environments provided by living cells.