Department of Physics, Lehigh University, Bethlehem, PA 18017, USA.
Department of Biological Sciences, Lehigh University, Bethlehem, PA 18017, USA.
Structure. 2024 Feb 1;32(2):242-252.e2. doi: 10.1016/j.str.2023.11.010. Epub 2023 Dec 15.
Cytokinesis of animal and fungi cells depends crucially on the anillin scaffold proteins. Fission yeast anillin-related Mid1 anchors cytokinetic ring precursor nodes to the membrane. However, it is unclear if both of its Pleckstrin Homology (PH) and C2 C-terminal domains bind to the membrane as monomers or dimers, and if one domain plays a dominant role. We studied Mid1 membrane binding with all-atom molecular dynamics near a membrane with yeast-like lipid composition. In simulations with the full C terminal region started away from the membrane, Mid1 binds through the disordered L3 loop of C2 in a vertical orientation, with the PH away from the membrane. However, a configuration with both C2 and PH initially bound to the membrane remains associated with the membrane. Simulations of C2-PH dimers show extensive asymmetric membrane contacts. These multiple modes of binding may reflect Mid1's multiple interactions with membranes, node proteins, and ability to sustain mechanical forces.
动物和真菌细胞的胞质分裂过程在很大程度上依赖于肌球蛋白结合蛋白支架。裂殖酵母肌球蛋白相关蛋白 Mid1 将胞质分裂环前体节点锚定在细胞膜上。然而，目前尚不清楚其两个 PH 和 C2 末端结构域是以单体还是二聚体的形式与膜结合，以及是否一个结构域起主导作用。我们使用具有酵母样脂质组成的膜附近的全原子分子动力学研究了 Mid1 的膜结合。在远离膜的起始的全长 C 末端区域模拟中， Mid1 通过 C2 的无序 L3 环以垂直取向与膜结合，PH 远离膜。然而，初始与膜结合的同时具有 C2 和 PH 的构型仍与膜结合。C2-PH 二聚体的模拟显示出广泛的不对称膜接触。这些多种结合模式可能反映了 Mid1 与膜、节点蛋白的多种相互作用以及维持机械力的能力。
