Department of Theoretical and Computational Molecular Science, Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki, 444-8585, Japan.
Institute for Solid State Physics, University of Tokyo, Kashiwa, Chiba, 277-8581, Japan.
Sci Rep. 2019 Oct 10;9(1):14557. doi: 10.1038/s41598-019-51202-z.
F-Bin/Amphiphysin/Rvs (F-BAR) domain proteins play essential roles in biological processes that involve membrane remodelling, such as endocytosis and exocytosis. It has been shown that such proteins transform the lipid membrane into tubes. Notably, Pacsin1 from the Pacsin/Syndapin subfamily has the ability to transform the membrane into various morphologies: striated tubes, featureless wide and thin tubes, and pearling vesicles. The molecular mechanism of this interesting ability remains elusive. In this study, we performed all-atom (AA) and coarse-grained (CG) molecular dynamics simulations to investigate the curvature induction and sensing mechanisms of Pacsin1 on a membrane. From AA simulations, we show that Pacsin1 has internal structural flexibility. In CG simulations with parameters tuned from the AA simulations, spontaneous assembly of two Pacsin1 dimers through lateral interaction is observed. Based on the complex structure, we show that the regularly assembled Pacsin1 dimers bend a tensionless membrane. We also show that a single Pacsin1 dimer senses the membrane curvature, binding to a buckled membrane with a preferred curvature. These results provide molecular insights into polymorphic membrane remodelling.
F-Bin/Amphiphysin/Rvs（F-BAR）域蛋白在涉及膜重塑的生物学过程中发挥着重要作用，如内吞作用和胞吐作用。已经表明，这些蛋白质可以将脂质膜转化为管状结构。值得注意的是，Pacsin/Syndapin 亚家族的 Pacsin1 具有将膜转化为各种形态的能力：条纹管状、无特征的宽而薄的管状和珠状囊泡。这种有趣能力的分子机制仍然难以捉摸。在这项研究中，我们进行了全原子（AA）和粗粒化（CG）分子动力学模拟，以研究 Pacsin1 在膜上的曲率诱导和感应机制。从 AA 模拟中，我们表明 Pacsin1 具有内部结构灵活性。在 CG 模拟中，使用从 AA 模拟中调整的参数，观察到两个 Pacsin1 二聚体通过横向相互作用自发组装。基于复杂结构，我们表明规则组装的 Pacsin1 二聚体弯曲无张力膜。我们还表明，单个 Pacsin1 二聚体可以感知膜曲率，与具有优选曲率的弯曲膜结合。这些结果为多态性膜重塑提供了分子见解。
