Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone

  1. Abhilash Padavannil
  2. Prithwijit Sarkar
  3. Seung Joong Kim
  4. Tolga Cagatay
  5. Jenny Jiou
  6. Chad A Brautigam
  7. Diana R Tomchick
  8. Andrej Sali
  9. Sheena D'Arcy
  10. Yuh Min Chook  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. University of Texas at Dallas, United States
  3. Korea Advanced Institute of Science and Technology (KAIST), Korea (South), Republic of
  4. University of California, San Francisco, United States

Abstract

We report the crystal structure of nuclear import receptor Importin-9 bound to its cargo, the histones H2A-H2B. Importin-9 wraps around the core, globular region of H2A-H2B to form an extensive interface. The nature of this interface coupled with quantitative analysis of deletion mutants of H2A-H2B suggest that the NLS-like sequences in the H2A-H2B tails play a minor role in import. Importin-9•H2A-H2B is reminiscent of interactions between histones and histone chaperones in that it precludes H2A-H2B interactions with DNA and H3-H4 as seen in the nucleosome. Like many histone chaperones, which prevent inappropriate non-nucleosomal interactions, Importin-9 also sequesters H2A-H2B from DNA. Importin-9 appears to act as a storage chaperone for H2A-H2B while escorting it to the nucleus. Surprisingly, RanGTP does not dissociate Importin-9•H2A-H2B but assembles into a RanGTP•Importin-9•H2A-H2B complex. The presence of Ran in the complex, however, modulates Imp9-H2A-H2B interactions to facilitate its dissociation by DNA and assembly into a nucleosome.

Data availability

Diffraction data have been deposited in PDB under the accession code 6N1Z

The following data sets were generated

Article and author information

Author details

  1. Abhilash Padavannil

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Prithwijit Sarkar

    Department of Biological Sciences, University of Texas at Dallas, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Seung Joong Kim

    Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.
  4. Tolga Cagatay

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jenny Jiou

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Chad A Brautigam

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Diana R Tomchick

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7529-4643
  8. Andrej Sali

    Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0435-6197
  9. Sheena D'Arcy

    Department of Chemistry and Biochemistry, University of Texas at Dallas, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5055-988X
  10. Yuh Min Chook

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    yuhmin.chook@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4974-0726

Funding

National Institutes of Health

  • Yuh Min Chook

Welch Foundation

  • Yuh Min Chook

Leukemia and Lymphoma Society

  • Yuh Min Chook

National Institutes of Health

  • Abhilash Padavannil
  • Tolga Cagatay
  • Jenny Jiou

National Institutes of Health

  • Chad A Brautigam
  • Diana R Tomchick
  • Andrej Sali

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

Reviewing Editor

  1. Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany

Version history

  1. Received: November 14, 2018
  2. Accepted: March 9, 2019
  3. Accepted Manuscript published: March 11, 2019 (version 1)
  4. Version of Record published: April 8, 2019 (version 2)

Copyright

© 2019, Padavannil 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. Abhilash Padavannil
  2. Prithwijit Sarkar
  3. Seung Joong Kim
  4. Tolga Cagatay
  5. Jenny Jiou
  6. Chad A Brautigam
  7. Diana R Tomchick
  8. Andrej Sali
  9. Sheena D'Arcy
  10. Yuh Min Chook
(2019)
Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone
eLife 8:e43630.
https://doi.org/10.7554/eLife.43630

Share this article

https://doi.org/10.7554/eLife.43630

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