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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Bibliographic Details
Published in:	eLife Vol. 7
Main Authors:	Healy, Michael D, Hospenthal, Manuela K, Hall, Ryan J, Chandra, Mintu, Chilton, Molly, Tillu, Vikas, Chen, Kai-En, Celligoi, Dion J, McDonald, Fiona J, Cullen, Peter J, Lott, J Shaun, Collins, Brett M, Ghai, Rajesh
Format:	Journal Article
Language:	English
Published:	England eLife Sciences Publications, Ltd 01-08-2018 eLife Sciences Publications Ltd
Subjects:	Adaptor Proteins, Signal Transducing - chemistry Adaptor Proteins, Signal Transducing - genetics Amino Acid Sequence CCC complex Cell Biology Commander complex copper metabolism Murr1 domain containing (COMMD) Crystallography, X-Ray endosome Endosomes - chemistry Endosomes - genetics Humans Intracellular Membranes - chemistry Intracellular Membranes - metabolism membrane trafficking Membrane Transport Proteins - chemistry Membrane Transport Proteins - genetics Membrane Transport Proteins - therapeutic use Multiprotein Complexes - chemistry Multiprotein Complexes - genetics Nuclear Magnetic Resonance, Biomolecular Protein Binding Protein Conformation, alpha-Helical Protein Domains Protein Interaction Mapping retriever Sequence Alignment Signal Transduction - genetics Structural Biology and Molecular Biophysics Transcription, Genetic endosome cell biology retriever Commander complex copper metabolism Murr1 domain containing (COMMD) CCC complex structural biology molecular biophysics human membrane trafficking
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, London, United Kingdom.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.35898