The nuclear pore complex (NPC) is responsible for the selective transport of biomolecules in and out of the nucleus. This selective feature is achieved through intrinsically disordered proteins, FG-Nups, that are anchored to the inner wall of the NPC. Cargo smaller than approximately 5 nm can rapidly diffuse through the NPC whereas larger cargo is increasingly slowed down. Larger cargos bound to chaperone proteins (from the karyopherin or Kap family) can still be transported due to nonspecific interactions with the FG-Nups. Although various mechanisms for the transport of Kaps have been proposed, a consensus has still to be reached. Here, we conducted a coarse-grained molecular dynamics study to shed light on Kap translocation through NPCs. We investigated the effect of Kap surface charge and hydrophobicity on the transport rate. We found that the negative charge of the Kaps is essential for transport whereas Kap hydrophobicity of the transport particle aids in the translocation. Interestingly, our results indicate that the positive net charge of the nuclear Nups (especially Nup1) is instrumental for the transport of Kaps, revealing a (previously proposed) gradient of increasing binding affinity of the Kaps with FG-Nups from the cytoplasm to the nucleus.

中文翻译：

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核蛋白电荷和核 FG-Nups 是核质转运的关键成分


核孔复合体 （NPC） 负责生物分子进出细胞核的选择性运输。这种选择性特征是通过锚定在 NPC 内壁的固有无序蛋白 FG-Nups 实现的。小于约 5 nm 的货物可以通过 NPC 迅速扩散，而较大的货物则越来越慢。由于与 FG-Nups 的非特异性相互作用，与伴侣蛋白（来自 karyopherin 或 Kap 家族）结合的较大货物仍然可以运输。尽管已经提出了各种 Kaps 运输机制，但仍需达成共识。在这里，我们进行了一项粗粒度分子动力学研究，以阐明 Kap 通过 NPC 的易位。我们研究了 Kap 表面电荷和疏水性对传输速率的影响。我们发现 Kaps 的负电荷对于运输至关重要，而运输颗粒的 Kap 疏水性有助于易位。有趣的是，我们的结果表明，核 Nup（尤其是 Nup1）的正净电荷有助于 Kaps 的运输，揭示了 Kaps 与 FG-Nups 的结合亲和力从细胞质到细胞核的（先前提出的）增加的梯度。