Nanocompartmentalization of the Nuclear Pore Lumen
Nanocompartmentalization of the Nuclear Pore Lumen
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DOI：
10.1016/j.bpj.2019.11.024
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发表时间：
2020-01-07
影响因子：
3.4
通讯作者：
Szleifer, Igal
中科院分区：
文献类型：
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作者：
Huang, Kai;Tagliazucchi, Mario;Szleifer, Igal
核孔复合物（NPC）利用富苯丙氨酸-甘氨酸核孔蛋白（gf - nups）家族中的内在无序区（IDRs）来控制核胞质运输。idr介导的物质交换是如何快速而又有选择性的，这一直是一个长期存在的谜团。在这里，我们使用计算显微镜来显示IDR亚域的纳米区隔化导致了一个由氨基酸序列编程的非常复杂的门控结构。特别是，我们揭示了一种非均质渗透性屏障，它结合了内环屏障和两种前庭凝聚物。在整个NPC中，我们发现了一个极化静电势和一个具有低FG-FG配对分数的马赛克FG区域的弥漫性热可逆FG网络。我们对中心转运蛋白的理论解剖揭示了FG-Nups的序列-结构-功能关系，并提供了核质质量交换的图像，从而实现了转运效率和特异性的协调。
The nuclear pore complex (NPC) employs the intrinsically disordered regions (IDRs) from a family of phenylalanine-glycine-rich nucleoporins (FG-Nups) to control nucleocytoplasmic transport. It has been a long-standing mystery how the IDR-mediated mass exchange can be rapid yet selective. Here, we use a computational microscope to show that nanocompartmentalization of IDR subdomains leads to a remarkably elaborate gating structure as programmed by the amino acid sequences. In particular, we reveal a heterogeneous permeability barrier that combines an inner ring barrier with two vestibular condensates. Throughout the NPC, we find a polarized electrostatic potential and a diffuse thermoreversible FG network featuring mosaic FG territories with low FG-FG pairing fraction. Our theoretical anatomy of the central transporter sheds light into the sequence-structure-function relationship of the FG-Nups and provides a picture of nucleocytoplasmic mass exchange that allows a reconciliation of transport efficiency and specificity.