Spatial structure of disordered proteins dictates conductance and selectivity in Nuclear Pore Complex mimics
- Kavli Institute of Nanoscience, Delft University of Technology, Netherlands
- University of Groningen, Netherlands
- Max Planck Institute for Biophysical Chemistry, Germany
Abstract
Nuclear pore complexes (NPCs) lined with intrinsically disordered FG-domains act as selective gatekeepers for molecular transport between the nucleus and the cytoplasm in eukaryotic cells. The underlying physical mechanism of the intriguing selectivity is still under debate. Here, we probe the transport of ions and transport receptors through biomimetic NPCs consisting of Nsp1 domains attached to the inner surface of solid-state nanopores. We examine both wildtype FG-domains and hydrophilic SG-mutants. FG-nanopores showed a clear selectivity as transport receptors can translocate across the pore whereas other proteins cannot. SG mutant pores lack such selectivity. To unravel this striking difference, we present coarse-grained molecular dynamics simulations that reveal that FG-pores exhibit a high-density, nonuniform protein distribution, in contrast to a uniform and significantly less-dense protein distribution in the SG-mutant. We conclude that the sequence-dependent density distribution of disordered proteins inside the NPC plays a key role for its conductivity and selective permeability.
Article and author information
Author details
Erik van der Giessen
Funding
Zernike Institute for Advanced Materials, University of Groningen
- Ankur Mishra
University Medical Center Groningen
- Ankur Mishra
NanoNextNL (program 637 07A.05)
- Cees Dekker
FOM and Netherlands Organization for Scientific Research
- Cees Dekker
ERC Advanced Grant SynDiv (grant number 669598)
- Cees Dekker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Ananth 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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Spatial structure of disordered proteins dictates conductance and selectivity in Nuclear Pore Complex mimics
eLife 7:e31510.
https://doi.org/10.7554/eLife.31510
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