Structural insights into the architecture and membrane interactions of the conserved COMMD proteins
- University of Queensland, Australia
- University of Auckland, New Zealand
- University of Bristol, United Kingdom
- 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.
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Crystal structure of Commd9 COMM domainPublicly available at the RCSB Protein Data Bank (accession no: 6BP6).
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The crystal structure of the n-terminal domain of COMMD9Publicly available at the RCSB Protein Data Bank (accession no: 4OE9).
Article and author information
Author details
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
- Sean Munro, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
Version history
- Received: February 14, 2018
- Accepted: July 31, 2018
- Accepted Manuscript published: August 1, 2018 (version 1)
- 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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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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