The nuclear pore complex (NPC) acts as a selective gate that mediates the bidirectional transport of macromolecules between the cytoplasm and the nucleus of eukaryotic cells. 'Natively unfolded' nucleoporins (Nups) with domains rich in phenylalanine-glycine (FG) repeats form the selective permeability barrier and provide binding sites for mobile transport receptors in the NPC. Understanding the structure and function of the FG-Nups barrier under real-time trafficking conditions is still a formidable challenge due to the dynamic nature of a channeled membranous environment. Recently, we have shown that three-dimensional (3D) density maps of transient interactions between the FG-Nups barrier and a cargo-free or a cargo-bound transport receptor in native NPCs can be obtained by an advanced single-molecule fluorescence microscopy approach. Moreover, we found that these interaction sites are spatially clustered into distinct groups in the periphery around a central axial channel with a diameter of approximately 10-20 nm in the NPC. The 3D distribution of interaction sites may indicate some native properties of the FG-Nups barrier. Here we speculate that the selective permeability barrier in the NPC could be formed by clustered FG-Nups.

中文翻译：

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核质运输中的“天然未折叠”核孔蛋白：成簇还是均匀分布？

核孔隙络合物（NPC）用作选择性栅极，其介导细胞质与真核细胞核之间的大分子双向传输。“天然未折叠”核孔蛋白 (Nups) 具有富含苯丙氨酸-甘氨酸 (FG) 重复序列的结构域，形成选择性渗透屏障，并为 NPC 中的移动转运受体提供结合位点。由于通道膜环境的动态特性，在实时贩运条件下了解 FG-Nups 屏障的结构和功能仍然是一项艰巨的挑战。最近，我们已经表明，可以通过先进的单分子荧光显微镜方法获得 FG-Nups 屏障与天然 NPC 中的无货物或货物结合转运受体之间瞬态相互作用的三维 (3D) 密度图. 此外，我们发现这些相互作用位点在空间上聚集成不同的组，在 NPC 中直径约为 10-20 nm 的中央轴向通道周围的外围。交互站点的 3D 分布可能表明 FG-Nups 屏障的一些原生特性。在这里，我们推测 NPC 中的选择性渗透屏障可以由成簇的 FG-Nups 形成。