Department of Chemistry, City College of New York, New York, NY 10031, USA.
Department of Chemistry, City College of New York, New York, NY 10031, USA; Graduate Programs in Chemistry, Biochemistry, and Physics, The Graduate Center, City University of New York, New York, NY, USA.
Structure. 2021 Dec 2;29(12):1440-1452.e4. doi: 10.1016/j.str.2021.07.010. Epub 2021 Sep 13.
The membrane sculpting ability of BAR domains has been attributed to the intrinsic curvature of their banana-shaped dimeric structure. However, there is often a mismatch between this intrinsic curvature and the diameter of the membrane tubules generated. I-BAR domains are especially mysterious since they are almost flat but generate high negative membrane curvature. Here, we use atomistic implicit-solvent computer modeling to show that the membrane bending of the IRSp53 I-BAR domain is dictated by its higher oligomeric structure, whose curvature is completely unrelated to the intrinsic curvature of the dimer. Two other I-BARs give similar results, whereas a flat F-BAR sheet develops a concave membrane-binding interface, consistent with its observed positive membrane curvature generation. Laterally interacting helical spirals of I-BAR dimers on tube interiors are stable and have an enhanced binding energy that is sufficient for membrane bending to experimentally observed tubule diameters at a reasonable surface density.
BAR 结构域的膜塑能力归因于其香蕉形二聚体结构的固有曲率。然而，这种固有曲率与所产生的膜小管直径之间常常存在不匹配。I-BAR 结构域特别神秘，因为它们几乎是平的，但却产生了很高的负膜曲率。在这里，我们使用原子隐式溶剂计算机建模来表明，IRSp53 I-BAR 结构域的膜弯曲是由其更高的聚合结构决定的，其曲率与二聚体的固有曲率完全无关。另外两个 I-BAR 结构域给出了类似的结果，而一个平坦的 F-BAR 片层则形成了一个凹面的膜结合界面，这与观察到的其产生正膜曲率的情况一致。在管内，I-BAR 二聚体的侧向相互作用的螺旋是稳定的，并且具有增强的结合能，足以使膜弯曲达到实验观察到的小管直径，而在合理的表面密度下。
