Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies

Abstract
Data availability
Article and author information
Metrics

Abstract

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.

Data availability

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.

The following data sets were generated

1. Davis LK
(2021) DFT-polymer-colloid
Github, ID: 164454451.

https://github.com/patherlkd/DFT-polymer-colloid

Article and author information

Author details

Luke K Davis

Department of Physics and Astronomy, University College London, London, United Kingdom

For correspondence
luke.davis@uni.lu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4487-4159
Ian J Ford

Department of Physics and Astronomy, University College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Bart W Hoogenboom

London Centre for Nanotechnology, University College London, London, United Kingdom

For correspondence
b.hoogenboom@ucl.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8882-4324

Funding

Engineering and Physical Sciences Research Council (EP/L504889/1)

Luke K Davis

Engineering and Physical Sciences Research Council (EP/L504889/1)

Bart W Hoogenboom

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

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.