Matsuda Atsushi, Mofrad Mohammad R K
Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California Berkeley, Berkeley, CA 94720.
Molecular Biophysics and Integrative Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.
Mol Biol Cell. 2024 Dec 1;35(12):ar149. doi: 10.1091/mbc.E24-05-0224. Epub 2024 Oct 30.
Macromolecules are transported through the nuclear pore complex (NPC) via a series of transient binding and unbinding events with FG-Nups, which are intrinsically disordered proteins anchored to the pore's inner wall. Prior studies suggest that the weak and transient nature of this binding is crucial for maintaining the transported molecules' diffusivity. In this study, we explored the relationship between binding kinetics and transport efficiency using Brownian dynamics simulations. Our results indicate that the duration of binding is a critical factor in regulating transport efficiency. Specifically, excessively short binding durations insufficiently facilitate transport, while overly long durations impede molecular movement. We calculated the optimal binding duration for efficient molecular transport and found that it aligns with other theoretical predictions. Additionally, the calculated value is comparable to experimental measurements of the association timescale between nuclear transport receptors and FG-Nups at a single binding site. Our study provides a quantitative framework that bridges local molecular interactions with overall transport dynamics through the NPC, offering valuable insights into the mechanisms governing selective molecular transport.
大分子通过与FG核孔蛋白发生一系列短暂的结合和解离事件，经由核孔复合体（NPC）进行转运，FG核孔蛋白是锚定在孔内壁的内在无序蛋白。先前的研究表明，这种结合的弱性和短暂性对于维持被转运分子的扩散性至关重要。在本研究中，我们使用布朗动力学模拟探索了结合动力学与转运效率之间的关系。我们的结果表明，结合持续时间是调节转运效率的关键因素。具体而言，过短的结合持续时间不足以促进转运，而过长的持续时间则会阻碍分子运动。我们计算了有效分子转运的最佳结合持续时间，发现它与其他理论预测相符。此外，计算值与核转运受体和单个结合位点处的FG核孔蛋白之间的结合时间尺度的实验测量值相当。我们的研究提供了一个定量框架，可以通过NPC将局部分子相互作用与整体转运动力学联系起来，为控制选择性分子转运的机制提供了有价值的见解。
