1. Structural Biology and Molecular Biophysics

Structure-based nuclear import mechanism of histones H3 and H4 mediated by Kap123

  1. Sojin An
  2. Jungmin Yoon
  3. Hanseong Kim
  4. Ji-Joon Song
  5. Uhn-soo Cho  Is a corresponding author
  1. University of Michigan Medical School, United States
  2. Korea Advanced Institute of Science and Technology, Korea (South), Republic of
https://doi.org/10.7554/eLife.30244
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  1. Sojin An
  2. Jungmin Yoon
  3. Hanseong Kim
  4. Ji-Joon Song
  5. Uhn-soo Cho
(2017)
Structure-based nuclear import mechanism of histones H3 and H4 mediated by Kap123
eLife 6:e30244.
https://doi.org/10.7554/eLife.30244
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Abstract

Kap123, a major karyopherin protein of budding yeast, recognizes the nuclear localization signals (NLSs) of cytoplasmic histones H3 and H4 and translocates them into the nucleus during DNA replication. Mechanistic questions include H3- and H4-NLS redundancy toward Kap123 and the role of the conserved diacetylation of cytoplasmic H4 (K5ac and K12ac) in Kap123-mediated histone nuclear translocation. Here, we report crystal structures of full-length Kluyveromyces lactis Kap123 alone and in complex with H3- and H4-NLSs. Structures reveal the unique feature of Kap123 that possesses two discrete lysine-binding pockets for NLS recognition. Structural comparison illustrates that H3- and H4-NLSs share at least one of two lysine-binding pockets, suggesting that H3- and H4-NLSs are mutually exclusive. Additionally, acetylation of key lysine residues at NLS, particularly H4-NLS diacetylation, weakens the interaction with Kap123. These data support that cytoplasmic histone H4 diacetylation weakens the Kap123-H4-NLS interaction thereby facilitating histone Kap123-H3-dependent H3:H4/Asf1 complex nuclear translocation.

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Article and author information

Author details

  1. Sojin An

    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Jungmin Yoon

    Structural Biology Laboratory of Epigenetics, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.

  3. Hanseong Kim

    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Ji-Joon Song

    Structural Biology Laboratory of Epigenetics, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.

  5. Uhn-soo Cho

    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, United States
    For correspondence
    uhnsoo@med.umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6992-2455

Funding

National Institutes of Health (DK111465)

  • Uhn-soo Cho

American Diabetes Association (1-16-JDF-017)

  • Uhn-soo Cho

National Institutes of Health (AG050903)

  • Uhn-soo Cho

March of Dimes Foundation (N019154-00)

  • Uhn-soo Cho

National Research Foundation of Korea (2016R1A2B3006293)

  • Ji-Joon Song

National Research Foundation of Korea (2013R1A1A2055605)

  • Ji-Joon Song

National Research Foundation of Korea (2014K2A3A1000137)

  • Ji-Joon Song

National Research Foundation of Korea (2011-0031955)

  • Ji-Joon Song

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

Reviewing Editor

  1. Eric Campos, The Hospital for Sick Children, Canada

Version history

  1. Received: July 7, 2017
  2. Accepted: October 12, 2017
  3. Accepted Manuscript published: October 16, 2017 (version 1)
  4. Version of Record published: November 8, 2017 (version 2)

Copyright

© 2017, An 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. Sojin An
  2. Jungmin Yoon
  3. Hanseong Kim
  4. Ji-Joon Song
  5. Uhn-soo Cho
(2017)
Structure-based nuclear import mechanism of histones H3 and H4 mediated by Kap123
eLife 6:e30244.
https://doi.org/10.7554/eLife.30244

Share this article

https://doi.org/10.7554/eLife.30244

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