Structural insights into the architecture and membrane interactions of the conserved COMMD proteins

  1. Michael D Healy
  2. Manuela K Hospenthal
  3. Ryan J Hall
  4. Mintu Chandra
  5. Molly Chilton
  6. Vikas Tillu
  7. Kai-En Chen
  8. Dion J Celligoi
  9. Fiona J McDonald
  10. Peter J Cullen
  11. J Shaun Lott
  12. Brett M Collins  Is a corresponding author
  13. Rajesh Ghai  Is a corresponding author
  1. University of Queensland, Australia
  2. University of Auckland, New Zealand
  3. University of Bristol, United Kingdom
  4. University of Otago, New Zealand

Abstract

The COMMD proteins are a conserved family of proteins with central roles in intracellular membrane trafficking and transcription. They form oligomeric complexes with each other and act as components of a larger assembly called the CCC complex, which is localized to endosomal compartments and mediates the transport of several transmembrane cargos. How these complexes are formed however is completely unknown. Here, we have systematically characterised the interactions between human COMMD proteins, and determined structures of COMMD proteins using X-ray crystallography and X-ray scattering to provide insights into the underlying mechanisms of homo- and heteromeric assembly. All COMMD proteins possess an a-helical N-terminal domain, and a highly conserved C‑terminal domain that forms a tightly interlocked dimeric structure responsible for COMMD-COMMD interactions. The COMM domains also bind directly to components of CCC and mediate non-specific membrane association. Overall these studies show that COMMD proteins function as obligatory dimers with conserved domain architectures.

Data availability

The raw biochemical data generated in this study is included in the supporting files. Diffraction data has been deposited in PDB and accession codes are provided in the manuscript.

The following data sets were generated
    1. Hospenthal M
    2. Celligoi D
    3. Lott JS
    (2015) The crystal structure of the n-terminal domain of COMMD9
    Publicly available at the RCSB Protein Data Bank (accession no: 4OE9).

Article and author information

Author details

  1. Michael D Healy

    Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2924-9179
  2. Manuela K Hospenthal

    School of Biological Sciences, University of Auckland, Auckland, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  3. Ryan J Hall

    Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8543-0370
  4. Mintu Chandra

    Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Molly Chilton

    School of Biochemistry, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2238-9822
  6. Vikas Tillu

    Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1034-9543
  7. Kai-En Chen

    Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Dion J Celligoi

    Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  9. Fiona J McDonald

    Department of Physiology, University of Otago, Dunedin, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  10. Peter J Cullen

    MRC Centre for Synaptic Plasticity, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. J Shaun Lott

    Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  12. Brett M Collins

    Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia
    For correspondence
    b.collins@imb.uq.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6070-3774
  13. Rajesh Ghai

    Institute for Molecular Bioscience, University of Queensland, St Lucia, Australia
    For correspondence
    r.ghai@uq.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0919-0934

Funding

National Health and Medical Research Council (1097185)

  • Rajesh Ghai

Australian Research Council (DP160101743)

  • Brett M Collins

Wellcome (89928)

  • Peter J Cullen

Royal Society of New Zealand

  • J Shaun Lott

National Health and Medical Research Council (APP1058734)

  • Brett M Collins

National Health and Medical Research Council (APP1061574)

  • Brett M Collins

Medical Research Council (MR/K018299/1)

  • Peter J Cullen

Wellcome (104568)

  • Peter J Cullen

Medical Research Council (MR/P018807/1)

  • Peter J Cullen

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

Reviewing Editor

  1. Sean Munro, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom

Publication history

  1. Received: February 14, 2018
  2. Accepted: July 31, 2018
  3. Accepted Manuscript published: August 1, 2018 (version 1)
  4. Version of Record published: August 13, 2018 (version 2)

Copyright

© 2018, Healy 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. Michael D Healy
  2. Manuela K Hospenthal
  3. Ryan J Hall
  4. Mintu Chandra
  5. Molly Chilton
  6. Vikas Tillu
  7. Kai-En Chen
  8. Dion J Celligoi
  9. Fiona J McDonald
  10. Peter J Cullen
  11. J Shaun Lott
  12. Brett M Collins
  13. Rajesh Ghai
(2018)
Structural insights into the architecture and membrane interactions of the conserved COMMD proteins
eLife 7:e35898.
https://doi.org/10.7554/eLife.35898

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