The rapid (< 1 ms) transport of biological material to and from the cell nucleus is regulated by the nuclear pore complex (NPC). At the core of the NPC is a permeability barrier consisting of intrinsically disordered Phe-Gly (FG) nucleoporins (FG Nups). Various types of nuclear transport receptors (NTRs) facilitate transport by partitioning in the FG Nup assembly, overcoming the barrier by their affinity to the FG Nups, and comprise a significant fraction of proteins in the NPC barrier. In previous work Zahn et al. (2016), we revealed a universal physical behaviour in the experimentally observed binding of two well-characterized NTRs, NTF2 and the larger Importin-β, to different planar assemblies of FG Nups, with the binding behaviour defined by negative cooperativity. This was further validated by a minimal physical model that treated the FG Nups as flexible homopolymers and the NTRs as uniformly cohesive spheres. Here, we build upon our original study by first parametrizing our model to experimental data, and next predicting the effects of crowding by different types of NTRs. We show how varying the amounts of one type of NTR modulates how the other NTR penetrates the FG Nup assembly. Notably, at similar and physiologically relevant NTR concentrations, our model predicts demixed phases of NTF2 and Imp-β within the FG Nup assembly. The functional implication of NTR phase separation is that NPCs may sustain separate transport pathways that are determined by inter-NTR competition.
The source code used to generate all the simulation data in this manuscript is available on the Github repository: https://github.com/patherlkd/DFT-polymer-colloid.Figure 1 - Source Code 1 - Simulation parameters for the classical density functional theory code.Figure 3 - Source Code 1 - Simulation parameters for the classical density functional theory code.
DFT-polymer-colloidGithub, ID: 164454451.
- Luke K Davis
- Bart W Hoogenboom
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Megan C King, Yale School of Medicine, United States
© 2022, Davis et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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