Coil-to-α-helix transition at the Nup358-BicD2 interface activates BicD2 for dynein recruitment

  1. James M Gibson
  2. Heying Cui
  3. M Yusuf Ali
  4. Xioaxin Zhao
  5. Erik W Debler
  6. Jing Zhao
  7. Kathleen M Trybus  Is a corresponding author
  8. Sozanne R Solmaz  Is a corresponding author
  9. Chunyu Wang  Is a corresponding author
  1. Rensselaer Polytechnic Institute, United States
  2. Binghamton University, United States
  3. University of Vermont, United States
  4. Thomas Jefferson University, United States

Abstract

Nup358, a protein of the nuclear pore complex, facilitates a nuclear positioning pathway that is essential for many biological processes, including neuromuscular and brain development. Nup358 interacts with the dynein adaptor Bicaudal D2 (BicD2), which in turn recruits the dynein machinery to position the nucleus. However, the molecular mechanisms of the Nup358/BicD2 interaction and the activation of transport remain poorly understood. Here for the first time, we show that a minimal Nup358 domain activates dynein/dynactin/BicD2 for processive motility on microtubules. Using nuclear magnetic resonance (NMR) titration and chemical exchange saturation transfer (CEST), mutagenesis and circular dichroism spectroscopy (CD), a Nup358 a-helix encompassing residues 2162-2184 was identified, which transitioned from a random coil to an a-helical conformation upon BicD2-binding and formed the core of the Nup358-BicD2 interface. Mutations in this region of Nup358 decreased the Nup358/BicD2 interaction, resulting in decreased dynein recruitment and impaired motility. BicD2 thus recognizes Nup358 though a 'cargo recognition a-helix', a structural feature that may stabilize BicD2 in its activated state and promote processive dynein motility.

Data availability

Protein backbone assignments have been deposited in the BMRB under accession code 5182. All other data generated or analyzed during this study are included in the manuscript and supporting files; Source Data files have been provided for Figures 1, 2, 3, 4, 5, 6, 7, and 8.

Article and author information

Author details

  1. James M Gibson

    Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9378-0135
  2. Heying Cui

    Department of Chemistry, Binghamton University, Binghamton, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. M Yusuf Ali

    Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Xioaxin Zhao

    Department of Biological Sciences, Binghamton University, Binghamton, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Erik W Debler

    Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2587-2150
  6. Jing Zhao

    Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Kathleen M Trybus

    Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, United States
    For correspondence
    Kathleen.Trybus@med.uvm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5583-8500
  8. Sozanne R Solmaz

    Department of Chemistry, Binghamton University, Binghamton, United States
    For correspondence
    ssolmaz@binghamton.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1703-3701
  9. Chunyu Wang

    Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, United States
    For correspondence
    wangc5@rpi.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5165-7959

Funding

NIH Office of the Director (R01 GM144578)

  • M Yusuf Ali
  • Sozanne R Solmaz
  • Chunyu Wang

NIH Office of the Director (CA206592)

  • Chunyu Wang

NIH Office of the Director (AG069039)

  • Chunyu Wang

NIH Office of the Director (R15 GM128119)

  • Sozanne R Solmaz

Chemistry Department and the Research Foundation of SUNY

  • Sozanne R Solmaz

NIH Office of the Director (R35 GM136288)

  • Kathleen M Trybus

NIH Office of the Director (R03 NS114115)

  • M Yusuf Ali

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

Reviewing Editor

  1. Andrew P Carter, MRC Laboratory of Molecular Biology, United Kingdom

Publication history

  1. Preprint posted: May 7, 2021 (view preprint)
  2. Received: October 14, 2021
  3. Accepted: February 28, 2022
  4. Accepted Manuscript published: March 1, 2022 (version 1)
  5. Accepted Manuscript updated: March 4, 2022 (version 2)
  6. Version of Record published: March 25, 2022 (version 3)
  7. Version of Record updated: April 8, 2022 (version 4)

Copyright

© 2022, Gibson 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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  1. James M Gibson
  2. Heying Cui
  3. M Yusuf Ali
  4. Xioaxin Zhao
  5. Erik W Debler
  6. Jing Zhao
  7. Kathleen M Trybus
  8. Sozanne R Solmaz
  9. Chunyu Wang
(2022)
Coil-to-α-helix transition at the Nup358-BicD2 interface activates BicD2 for dynein recruitment
eLife 11:e74714.
https://doi.org/10.7554/eLife.74714
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