1. Structural Biology and Molecular Biophysics
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Spatial structure of disordered proteins dictates conductance and selectivity in Nuclear Pore Complex mimics

  1. Adithya N Ananth
  2. Ankur Mishra
  3. Steffen Frey
  4. Arvind Dwarkasing
  5. Roderick Versloot
  6. Erik van der Giessen
  7. Dirk Görlich  Is a corresponding author
  8. Patrick Onck  Is a corresponding author
  9. Cees Dekker  Is a corresponding author
  1. Kavli Institute of Nanoscience, Delft University of Technology, Netherlands
  2. University of Groningen, Netherlands
  3. Max Planck Institute for Biophysical Chemistry, Germany
Research Article
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Cite this article as: eLife 2018;7:e31510 doi: 10.7554/eLife.31510

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

  1. Adithya N Ananth

    Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Ankur Mishra

    Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Steffen Frey

    Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Arvind Dwarkasing

    Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Roderick Versloot

    Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Erik van der Giessen

    Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8369-2254
  7. Dirk Görlich

    Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    For correspondence
    dgoerli@gwdg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4343-5210
  8. Patrick Onck

    Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands
    For correspondence
    p.r.onck@rug.nl
    Competing interests
    The authors declare that no competing interests exist.
  9. Cees Dekker

    Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands
    For correspondence
    C.Dekker@tudelft.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6273-071X

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.

Reviewing Editor

  1. Richard M Berry, University of Oxford, United Kingdom

Publication history

  1. Received: August 24, 2017
  2. Accepted: February 5, 2018
  3. Accepted Manuscript published: February 14, 2018 (version 1)
  4. Version of Record published: February 26, 2018 (version 2)
  5. Version of Record updated: November 13, 2018 (version 3)

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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