Quantitative analysis of Nup58/Nup54 conformers that interact with karyopherin (Kap)
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Kap binding to a disordered region of Nup58 affects its neighboring ordered region
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Kap binding stabilizes the interaction of Nup54 with the ordered region of Nup58
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Quantitative model for Kap-mediated gating of the midplane ring of the nuclear pore
Summary
The nuclear pore complex (NPC) arose in evolution as the cell’s largest and most versatile transport channel. Current models for selective transport mediated by NPCs are focused on properties of intrinsically disordered regions of nucleoporins that bind transport factors. In contrast, structured regions are considered to provide static anchoring sites for the disordered regions without affecting transport factor binding. Here, we demonstrate allosteric coupling between a structured domain of a channel nucleoporin (Nup58) and its neighboring disordered domain in interaction with another channel nucleoporin (Nup54) and a transport factor (Kapβ1). Analysis of multiple equilibria showed that multivalent interactions of Kapβ1 with the disordered domains of Nup58 stabilize the neighboring structured domain associated with Nup54, shifting conformational equilibria from homo-oligomers to hetero-oligomers. Based on these and previous crystallographic results, a quantitative framework was established to describe constriction and dilation of the central channel as a function of transport factor occupancy.
