1. Structural Biology and Molecular Biophysics
  2. Chromosomes and Gene Expression
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Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes

  1. Ramasubramanian Sundaramoorthy
  2. Amanda L Hughes
  3. Vijender Singh
  4. Nicola Wiechens
  5. Daniel P Ryan
  6. Hassane El-Mkami
  7. Maxim Petoukhov
  8. Dmitri I svergun
  9. Barbara Treutlein
  10. Salina Quack
  11. Monika Fischer
  12. Jens Michaelis
  13. Bettina Böttcher
  14. David G Norman
  15. Tom Owen-Hughes  Is a corresponding author
  1. University of Dundee, United Kingdom
  2. The Australian National University, Australia
  3. University of St Andrews, United Kingdom
  4. European Molecular Biology Laboratory, Germany
  5. Max Planck Institute for Evolutionary Anthropolgy, Germany
  6. Ulm University, Germany
  7. Universitat Würzburg, Germany
Research Article
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Cite this article as: eLife 2017;6:e22510 doi: 10.7554/eLife.22510

Abstract

The yeast Chd1 protein acts to position nucleosomes across genomes. Here we model the structure of the Chd1 protein in solution and when bound to nucleosomes. In the apo state the DNA binding domain contacts the edge of the nucleosome while in the presence of the non-hydrolyzable ATP analog, ADP-beryllium fluoride, we observe additional interactions between the ATPase domain and the adjacent DNA gyre 1.5 helical turns from the dyad axis of symmetry. Binding in this conformation involves unravelling the outer turn of nucleosomal DNA and requires substantial reorientation of the DNA binding domain with respect to the ATPase domains. The orientation of the DNA-binding domain is mediated by sequences in the N-terminus and mutations to this part of the protein have positive and negative effects on Chd1 activity. These observations indicate that the unfavourable alignment of C-terminal DNA binding region in solution contributes to an auto-inhibited state.

Article and author information

Author details

  1. Ramasubramanian Sundaramoorthy

    Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Amanda L Hughes

    Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Vijender Singh

    Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Nicola Wiechens

    Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Daniel P Ryan

    Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9842-2620
  6. Hassane El-Mkami

    School of Physics and Astronomy, University of St Andrews, St Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Maxim Petoukhov

    Hamburg Outstation, European Molecular Biology Laboratory, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Dmitri I svergun

    Hamburg Outstation, European Molecular Biology Laboratory, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Barbara Treutlein

    Max Planck Institute for Evolutionary Anthropolgy, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Salina Quack

    Institute for Biophysics, Ulm University, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Monika Fischer

    Institute for Biophysics, Ulm University, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Jens Michaelis

    Institute for Biophysics, Ulm University, Ulm, Germany
    Competing interests
    The authors declare that no competing interests exist.
  13. Bettina Böttcher

    Lehrstuhl für Biochemie, Universitat Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  14. David G Norman

    Nucelic Acids Structure Research Group, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7658-7720
  15. Tom Owen-Hughes

    Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom
    For correspondence
    t.a.owenhughes@dundee.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0618-8185

Funding

Wellcome (95062)

  • Ramasubramanian Sundaramoorthy
  • Amanda L Hughes
  • Vijender Singh
  • Nicola Wiechens
  • Tom Owen-Hughes

Wellcome (097945/B/11/Z)

  • Ramasubramanian Sundaramoorthy
  • Amanda L Hughes
  • Vijender Singh
  • Nicola Wiechens
  • Tom Owen-Hughes

Wellcome (099149/Z/12/Z)

  • Ramasubramanian Sundaramoorthy
  • Hassane El-Mkami
  • David G Norman
  • Tom Owen-Hughes

Wellcome (97945)

  • Ramasubramanian Sundaramoorthy
  • Amanda L Hughes
  • Nicola Wiechens
  • Daniel P Ryan
  • David G Norman
  • Tom Owen-Hughes

European Molecular Biology Organization (ALTF 380-2015)

  • Amanda L Hughes

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

Reviewing Editor

  1. Timothy Formosa, University of Utah, United States

Publication history

  1. Received: November 9, 2016
  2. Accepted: March 15, 2017
  3. Accepted Manuscript published: March 23, 2017 (version 1)
  4. Version of Record published: April 13, 2017 (version 2)

Copyright

© 2017, Sundaramoorthy 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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