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bioRxiv · 10.1101/2024.06.23.600256

Nuclear transport at full amino-acid resolution

Dekker, M.·de Vries, H. W.·Wortelboer, K. A.·Beekhuis, H. J.·Van der Giessen, E.·Onck, P. R.
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Abstract

Recent studies of nuclear pore complexes (NPCs) have provided detailed descriptions of the core scaffold structures, yet fall short in resolving the dynamic FG-meshwork with similar precision. Here, we present a novel modeling framework that enables the simulation of nuclear transport at full amino-acid resolution. We describe the distributions of the different FG-Nups in the central transporter and highlight the dynamic nature of the FG-meshwork, with FG-FG interaction lifetimes on the order of nanoseconds. Our findings reveal that Nsp1, the most abundant FG-Nup in the NPC, creates a central meshwork due to its unique bimodal structure, that is essential for controlling both passive and active transport. By adding nuclear transport receptors (NTRs)--specifically Kap95--to the pore, we demonstrate that NTRs play a key role in increasing the energy barrier for translocation of inert particles. The NTRs are subject to a dynamic interplay between binding to FG motifs and the temporal fluctuations of the FG-meshwork, leading to transient voids through which they move. Overall, our simulations identify a dense GLFG-ring coated by lower-mobility Kaps and a central dynamic FG-FG meshwork to create a reduced-dimensional transport surface of optimal binding avidity that drives Kap translocation.

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Dekker, M., de Vries, H. W., Wortelboer, K. A., Beekhuis, H. J., Van der Giessen, E., Onck, P. R.. 2024-06-25. Nuclear transport at full amino-acid resolution. https://doi.org/10.1101/2024.06.23.600256

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