德国美因茨分子生物学研究所Edward A. Lemke课题组宣布他们的最新研究探明了糖基化和进口蛋白液化了活核孔中的FG屏障。相关论文于2026年11月11日发表在《自然》杂志上。

核孔复合物（NPC）调控细胞核与细胞质之间的分子运输。其通透性屏障由内在无序的富含苯丙氨酸-甘氨酸的核孔蛋白（FG-NUPs）形成，这些蛋白的物理状态长期以来存在争议。解析FG-NUPs在活细胞内的行为，对于理解NPC如何实现既选择性又快速的运输至关重要。在此，研究人员将位点特异性标记与时间分辨荧光各向异性技术相结合，表明FG结构域在活细胞中表现出纳秒尺度的液体样链段运动，而重构的FG凝聚体在体外则经历液-固转变。实验和分子动力学模拟进一步表明，主要核运输受体输入蛋白-β和FG-NUPs的关键翻译后修饰O-连接β-N-乙酰葡糖胺共同稳定了这一动态FG网络。精细平衡的FG–FG和FG–输入蛋白-β相互作用维持FG-NUP的液态，并产生一种径向组织，其中输入蛋白-β富集于NPC周边，而延伸的FG结构域保留在中央通道，形成运输屏障。这种组织方式解释了近期MINFLUX观察到的偏向周边的运输轨迹，并在此得到哺乳动物细胞中输入蛋白-β直接MINFLUX成像的支持。总之，研究结果调和了关于FG-NUP组织的相互冲突的模型，并为理解细胞环境如何在健康和疾病中调节内在无序蛋白建立了框架。

附：英文原文

Title: Glycosylation and importins liquefy the FG barrier in live nuclear pores

Author: Yu, Miao, Heidari, Maziar, Palacio-Rodriguez, Karen, Ruan, Hao, Mingu, Sara, Chen, Yu, Gou, Xu-Zhuo, Shen, Pingkai, Liu, Songzi, Chen, Si-Yu, Hidayat, Alam Ahmad, Bode, Mathis, Sikora, Mateusz, Tang, Ai-Hui, Hummer, Gerhard, Lemke, Edward A.

Issue&Volume: 2026-11-11

Abstract: The nuclear pore complex (NPC) regulates molecular traffic between nucleus and cytoplasm1,2. Its permeability barrier is formed by intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG-NUPs), whose physical state has long been debated3,4,5,6,7,8,9,10,11,12,13. Deciphering how FG-NUPs behave inside living cells is crucial for understanding how NPCs achieve both selective and rapid transport. By combining site-specific labelling with time-resolved fluorescence anisotropy, here we show that FG domains exhibit nanosecond-scale, liquid-like segmental motion in live cells, whereas reconstituted FG condensates undergo a liquid-to-solid transition in vitro. Experiments and molecular-dynamics simulations further show that importin-β, a principal nuclear transport receptor, and O-linked β-N-acetylglucosamine, a key post-translational modification of FG-NUPs, together stabilize the dynamic FG network. Finely balanced FG–FG and FG–importin-β interactions maintain FG-NUP liquidity and generate a radial organization in which importin-β is enriched near the NPC periphery and extended FG domains remain in the central channel, forming the transport barrier. This organization explains recent MINFLUX observations14 of rim-biased transport trajectories and is supported here by direct MINFLUX imaging of importin-β in mammalian cells. Together, our results reconcile conflicting models of FG-NUP organization4,5,7,9,15 and establish a framework for understanding how cellular context tunes intrinsically disordered proteins in health and disease.

DOI: 10.1038/s41586-026-11258-0

Source: https://www.nature.com/articles/s41586-026-11258-0