Structure and interactions of the endogenous human Commander complex
Open accessPublished version of a preprint
Abstract
The Commander complex, a 16-protein assembly, plays multiple roles in cell homeostasis, cell cycle and immune response. It consists of copper-metabolism Murr1 domain proteins (COMMD1–10), coiled-coil domain-containing proteins (CCDC22 and CCDC93), DENND10 and the Retriever subcomplex (VPS26C, VPS29 and VPS35L), all expressed ubiquitously in the body and linked to various diseases. Here, we report the structure and key interactions of the endogenous human Commander complex by cryogenic-electron microscopy and mass spectrometry-based proteomics. The complex consists of a stable core of COMMD1–10 and an effector containing DENND10 and Retriever, scaffolded together by CCDC22 and CCDC93. We establish the composition of Commander and reveal major interaction interfaces. These findings clarify its roles in intracellular transport, and uncover a strong association with cilium assembly, and centrosome and centriole functions.
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- Authors
- Laulumaa, S., Kumpula, E.-P., Huiskonen, J. T., & Varjosalo, M.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Huiskonen, Juha T.
- Varjosalo, Markku
- Venue
- Nature Structural & Molecular Biology
- Published
- 2024-03-08
- Volume
- 31
- Issue
- 6
- Pages
- 925-938
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC11189303
- OpenAlex
- W4392596901
- Cited by
- 46
- References
- 7
- Citations by year
- 2026: 7 · 2025: 22 · 2024: 15 · 2023: 2
- FWCI
- 10.34
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-03-19)
- Open access
- hybrid
- doi.org
- Locations
- Nature Structural & Molecular Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Research Square (acceptedVersion, cc-by)
- SSRN Electronic Journal (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- Funders
- Helsingin Yliopisto
- Kempe Foundation
- China Scholarship Council
- Umeå Universitet
- Kempestiftelserna
- Stockholms Universitet
- Science for Life Laboratory
- Biocenter Finland
- Helsinki Institute of Life Science, Helsingin Yliopisto
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- VPS29, protein complex structure, protein-protein interaction, copper metabolism, intracellular transport, centrosome, centrioles, cell cycle
- MeSH terms
- Centrioles, Cilia, Humans, Models, Molecular, Protein Binding, Cryoelectron Microscopy, Vesicular Transport Proteins, Multiprotein Complexes, Adaptor Proteins, Signal Transducing, HEK293 Cells
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