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Channel width modulates the permeability of DNA origami–based nuclear pore mimics
Science Advances ( IF 11.7 ) Pub Date : 2024-11-13 , DOI: 10.1126/sciadv.adq8773
Qingzhou Feng, Martin Saladin, Chunxiang Wu, Eason Cao, Wei Zheng, Amy Zhang, Pushpanjali Bhardwaj, Xia Li, Qi Shen, Larisa E. Kapinos, Toshiya Kozai, Malaiyalam Mariappan, C. Patrick Lusk, Yong Xiong, Roderick Y. H. Lim, Chenxiang Lin

Nucleoporins (nups) in the nuclear pore complex (NPC) form a selective barrier that suppresses the diffusion of most macromolecules while enabling rapid transport of nuclear transport receptor (NTR)–bound cargos. Recent studies have shown that the NPC may dilate and constrict, but how altering the NPC diameter affects its selective barrier properties remains unclear. Here, we build DNA nanopores with programmable diameters and nup arrangements to model the constricted and dilated NPCs. We find that Nup62 proteins form a dynamic cross-channel barrier impermeable to hepatitis B virus (HBV) capsids when grafted inside 60-nm-wide nanopores but not in 79-nm pores, where Nup62 cluster locally. Furthermore, importin-β1 substantially changes the dynamics of Nup62 assemblies and facilitates the passage of HBV capsids through the 60-nm NPC mimics containing Nup62 and Nup153. Our study shows that transport channel width is critical to the permeability of nup barriers and underscores NTRs’ role in dynamically remodeling nup assemblies and mediating the nuclear entry of viruses.

中文翻译:


通道宽度调节基于 DNA 折纸的核孔模拟物的通透性



核孔蛋白 (nups) 在核孔复合体 (NPC) 中形成选择性屏障,抑制大多数大分子的扩散,同时能够快速运输核转运受体 (NTR) 结合的货物。最近的研究表明,NPC 可能会扩张和收缩,但改变 NPC 直径如何影响其选择性屏障特性仍不清楚。在这里,我们构建了具有可编程直径和 nup 排列的 DNA 纳米孔,以模拟收缩和扩张的 NPC。我们发现,当 Nup62 蛋白嫁接在 60 nm 宽的纳米孔内时,会形成对乙型肝炎病毒 (HBV) 衣壳不透的动态跨通道屏障,但在 Nup62 局部聚集的 79 nm 孔中则不通透。此外,importin-β1 显着改变了 Nup62 组装体的动力学,并促进了 HBV 衣壳通过含有 Nup62 和 Nup153 的 60 nm NPC 模拟物。我们的研究表明,运输通道宽度对 nup 屏障的渗透性至关重要,并强调了 NTR 在动态重塑 nup 组件和介导病毒核进入中的作用。
更新日期:2024-11-13
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