Structural insights into the architecture and membrane interactions of the conserved COMMD proteins
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 mediate...
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doaj-52ef44e3fdd642e78e446da5ae0c2ac62021-05-05T16:03:36ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.35898Structural insights into the architecture and membrane interactions of the conserved COMMD proteinsMichael D Healy0https://orcid.org/0000-0003-2924-9179Manuela K Hospenthal1Ryan J Hall2https://orcid.org/0000-0002-8543-0370Mintu Chandra3Molly Chilton4https://orcid.org/0000-0003-2238-9822Vikas Tillu5https://orcid.org/0000-0002-1034-9543Kai-En Chen6https://orcid.org/0000-0003-1106-1629Dion J Celligoi7Fiona J McDonald8Peter J Cullen9J Shaun Lott10https://orcid.org/0000-0003-3660-452XBrett M Collins11https://orcid.org/0000-0002-6070-3774Rajesh Ghai12https://orcid.org/0000-0002-0919-0934Institute for Molecular Bioscience, The University of Queensland, St. Lucia, AustraliaSchool of Biological Sciences, The University of Auckland, Auckland, New ZealandInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, AustraliaSchool of Biochemistry, Biomedical Sciences Building, University of Bristol, Bristol, United KingdomInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, AustraliaSchool of Biological Sciences, The University of Auckland, Auckland, New ZealandDepartment of Physiology, University of Otago, Dunedin, New ZealandSchool of Biochemistry, Biomedical Sciences Building, University of Bristol, Bristol, United KingdomSchool of Biological Sciences, The University of Auckland, Auckland, New ZealandInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St. Lucia, AustraliaThe 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 α-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.https://elifesciences.org/articles/35898endosomemembrane traffickingcopper metabolism Murr1 domain containing (COMMD)retrieverCCC complexCommander complex |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michael D Healy Manuela K Hospenthal Ryan J Hall Mintu Chandra Molly Chilton Vikas Tillu Kai-En Chen Dion J Celligoi Fiona J McDonald Peter J Cullen J Shaun Lott Brett M Collins Rajesh Ghai |
spellingShingle |
Michael D Healy Manuela K Hospenthal Ryan J Hall Mintu Chandra Molly Chilton Vikas Tillu Kai-En Chen Dion J Celligoi Fiona J McDonald Peter J Cullen J Shaun Lott Brett M Collins Rajesh Ghai Structural insights into the architecture and membrane interactions of the conserved COMMD proteins eLife endosome membrane trafficking copper metabolism Murr1 domain containing (COMMD) retriever CCC complex Commander complex |
author_facet |
Michael D Healy Manuela K Hospenthal Ryan J Hall Mintu Chandra Molly Chilton Vikas Tillu Kai-En Chen Dion J Celligoi Fiona J McDonald Peter J Cullen J Shaun Lott Brett M Collins Rajesh Ghai |
author_sort |
Michael D Healy |
title |
Structural insights into the architecture and membrane interactions of the conserved COMMD proteins |
title_short |
Structural insights into the architecture and membrane interactions of the conserved COMMD proteins |
title_full |
Structural insights into the architecture and membrane interactions of the conserved COMMD proteins |
title_fullStr |
Structural insights into the architecture and membrane interactions of the conserved COMMD proteins |
title_full_unstemmed |
Structural insights into the architecture and membrane interactions of the conserved COMMD proteins |
title_sort |
structural insights into the architecture and membrane interactions of the conserved commd proteins |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-08-01 |
description |
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 α-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. |
topic |
endosome membrane trafficking copper metabolism Murr1 domain containing (COMMD) retriever CCC complex Commander complex |
url |
https://elifesciences.org/articles/35898 |
work_keys_str_mv |
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1721459660125372416 |