Conformational dynamics of the nuclear pore complex central channel.

The nuclear pore complex (NPC) is a vital regulator of molecular transport between the nucleus and cytoplasm in eukaryotic cells. At the heart of the NPC's function are intrinsically disordered phenylalanineglycine-rich nucleoporins (FG-Nups), which form a dynamic permeability barrier within the central channel. This disordered nature facilitates efficient nucleocytoplasmic transport but also poses significant challenges to its characterization, especially within the nano-confined environment of the NPC. Recent advances in experimental techniques, such as cryo-electron microscopy, atomic force microscopy, fluorescence microscopy, and nuclear magnetic resonance, along with computational modeling, have illuminated the conformational flexibility of FG-Nups, which underpins their functional versatility. This review synthesizes these advancements, emphasizing how disruptions in FG-Nup behavior-caused by mutations or pathological interactions-contribute to diseases such as neurodegenerative disorders, aging-related decline, and viral infections. Despite progress, challenges persist in deciphering FG-Nup dynamics within the crowded and complex cellular environment, especially under pathological conditions. Addressing these gaps is critical for advancing therapeutic strategies targeting NPC dysfunction in disease progression. © 2025 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

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Yu Chen, Guoli Zhou, Miao Yu. Conformational dynamics of the nuclear pore complex central channel. Biochemical Society transactions. 2025 Feb 07;53(1)

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PMID: 39927798

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