Data from: Cooperative interactions between different classes of disordered proteins play a functional role in the nuclear pore complex of Baker's yeast

Nucleocytoplasmic transport is highly selective, efficient, and is regulated by a poorly understood mechanism involving hundreds of disordered FG nucleoporin proteins (FG nups) lining the inside wall of the nuclear pore complex (NPC). Previous research has concluded that FG nups in Baker's yeast (S. cerevisiae) are present in a bimodal distribution, with the ``Forest Model'' classifying FG nups as either di-block polymer like ``trees'' or single-block polymer like ``shrubs''. Using a combination of coarse-grained modeling and polymer brush modeling, the function of the di-block FG nups has been hypothesized in the Di-block Copolymer Brush Gate (DCBG) model to form a higher-order polymer brush architecture which can open and close to regulate transport across the NPC. Here we perform coarse grained simulations of the single-block FG nups which confirm that they have a single block polymer structure rather than the di-block structure of tree nups. Our molecular simulations also demonstrate that these single-block FG nups are likely cohesive, compact, collapsed coil polymers, implying that these FG nups are generally localized to their grafting location within the NPC. We find that adding a layer of single-block FG nups to the DCBG model increases the range of cargo sizes which are able to translocate the pore through a cooperative effect involving single-block and di-block FG nups. This effect can explain the puzzling connection between single-block FG nup deletion mutants in S. cerevisiae and the resulting failure of certain large cargo transport through the NPC. Facilitation of large cargo transport via single-block and di-block FG nup cooperativity in the nuclear pore could provide a model mechanism for designing future biomimetic pores of greater applicability.

核质运输（nucleocytoplasmic transport）具有高度选择性与高效性，其调控机制尚未完全阐明，该过程涉及数百个无序的FG核孔蛋白（FG nucleoporin proteins, FG nups），这些蛋白排布于核孔复合体（nuclear pore complex, NPC）的内壁。既往研究表明，酿酒酵母（Baker's yeast, S. cerevisiae）中的FG核孔蛋白呈现双峰分布，“森林模型”将其分为两类：类二嵌段聚合物的“树木”型FG核孔蛋白，以及类单嵌段聚合物的“灌木”型FG核孔蛋白。结合粗粒度建模（coarse-grained modeling）与聚合物刷建模（polymer brush modeling），二嵌段FG核孔蛋白的功能可通过二嵌段聚合物刷门控（Di-block Copolymer Brush Gate, DCBG）模型进行假说性阐释：该模型认为此类蛋白可形成高阶聚合物刷结构，通过开闭来调控跨核孔复合体的运输过程。本研究针对单嵌段FG核孔蛋白开展粗粒度模拟，结果证实其确实为单嵌段聚合物结构，而非“树木”型的二嵌段结构。分子模拟（molecular simulations）还显示，这类单嵌段FG核孔蛋白属于具有凝聚性、紧凑性的塌陷卷曲聚合物，这意味着它们通常局限于核孔复合体内部的接枝位点。我们发现，在DCBG模型中添加单嵌段FG核孔蛋白层后，通过单嵌段与二嵌段FG核孔蛋白的协同作用，可跨孔转运的货物尺寸范围得以扩大。这一效应能够解释酿酒酵母中单嵌段FG核孔蛋白缺失突变体与特定大型货物无法通过核孔复合体转运之间的令人困惑的关联。借助核孔内单嵌段与二嵌段FG核孔蛋白的协同作用促进大型货物运输，这一机制可为设计适用性更广的下一代仿生孔提供模型参考。