Crystallography, Max Delbrück Center for Molecular Medicine, Berlin, Germany; Department of Physical Chemistry, Fritz Haber Institute of the Max Planck Society, Berlin, Germany.
Department of Mathematics and Computer Science.
Biophys J. 2019 Nov 19;117(10):1870-1891. doi: 10.1016/j.bpj.2019.09.042. Epub 2019 Oct 9.
Peripheral membrane proteins with intrinsic curvature can act both as sensors of membrane curvature and shape modulators of the underlying membranes. A well-studied example of such proteins is the mechanochemical GTPase dynamin, which assembles into helical filaments around membrane tubes and catalyzes their scission in a GTPase-dependent manner. It is known that the dynamin coat alone, without GTP, can constrict membrane tubes to radii of ∼10 nm, indicating that the intrinsic shape and elasticity of dynamin filaments should play an important role in membrane remodeling. However, molecular and dynamic understanding of the process is lacking. Here, we develop a dynamical polymer-chain model for a helical elastic filament bound on a deformable membrane tube of conserved mass, accounting for thermal fluctuations in the filament and lipid flows in the membrane. The model is based on the locally cylindrical helix approximation for dynamin. We obtain the elastic parameters of the dynamin filament by molecular dynamics simulations of its tetrameric building block and also from coarse-grained structure-based simulations of a 17-dimer filament. The results show that the stiffness of dynamin is comparable to that of the membrane. We determine equilibrium shapes of the filament and the membrane and find that mostly the pitch of the filament, not its radius, is sensitive to variations in membrane tension and stiffness. The close correspondence between experimental estimates of the inner tube radius and those predicted by the model suggests that dynamin's "stalk" region is responsible for its GTP-independent membrane-shaping ability. The model paves the way for future mesoscopic modeling of dynamin with explicit motor function.
具有内在曲率的外周膜蛋白可以充当膜曲率的传感器和基础膜形状调节剂。此类蛋白的一个很好的例子是机械化学 GTP 酶 dynamin，它在膜管周围组装成螺旋丝，并以 GTP 依赖性方式催化它们的断裂。众所周知，单独的 dynamin 外壳，没有 GTP，就可以将膜管收缩到约 10nm 的半径，这表明 dynamin 丝的固有形状和弹性应该在膜重塑中发挥重要作用。然而，对这个过程的分子和动态理解还很缺乏。在这里，我们为绑定在具有保守质量的可变形膜管上的螺旋弹性丝开发了一个动态聚合物链模型，该模型考虑了细丝中的热波动和膜中的脂质流动。该模型基于 dynamin 的局部圆柱螺旋近似。我们通过其四聚体构建块的分子动力学模拟以及基于粗粒结构的 17 聚体细丝的模拟获得了 dynamin 细丝的弹性参数。结果表明，dynamin 的刚度与膜的刚度相当。我们确定了细丝和膜的平衡形状，并发现主要是细丝的螺距，而不是其半径，对膜张力和刚度的变化敏感。实验估计的内管半径与模型预测值之间的紧密对应表明，dynamin 的“茎”区域负责其 GTP 独立的膜成型能力。该模型为具有显式运动功能的 dynamin 的未来介观建模铺平了道路。
