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Asynchronous structural rearrangements govern constriction of the human nuclear pore complex

Ding, E.; Mello, M. F.; Contessoto, V. G.; Oliveira, R. J.; Whitford, P. C.; Onuchic, J. N.

2026-08-01 biophysics
10.64898/2026.07.31.742064 bioRxiv
Show abstract

The nuclear pore complex (NPC) is responsible for transport between the cytoplasm and nucleus. CryoET experiments have resolved multiple conformations of the pore that are dilated or constricted. Since the dilation state will impact transport properties, there is much interest in understanding the energetic factors that regulate dilation/constriction. To this end, we applied a structure-based (G[o]-like) model to study the mechanistic properties of large-scale constriction ( [~] 100[A]) in the human NPC. Even though the structures are symmetric, the simulations implicate asynchronous rear-rangements during constriction. By considering variants of the model, we further characterize the relative contributions of individual proteins to this collective process. Together, this provides an energetic/structural foundation that can guide development of precise physical approaches for studying this elusive motion.

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