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TitleStructure and interactions of the endogenous human Commander complex.
Journal, issue, pagesNat Struct Mol Biol, Year 2024
Publish dateMar 8, 2024
AuthorsSaara Laulumaa / Esa-Pekka Kumpula / Juha T Huiskonen / Markku Varjosalo /
PubMed AbstractThe 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 ...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.
External linksNat Struct Mol Biol / PubMed:38459129
MethodsEM (single particle)
Resolution2.9 - 7.5 Å
Structure data

17339

8p0v

EMDB-17339, PDB-8p0v:
Structure of the human Commander complex coiled coils, DENND10 and partial Retriever subcomplex
Method: EM (single particle) / Resolution: 6.5 Å

17340

8p0w

EMDB-17340, PDB-8p0w:
Structure of the human Commander complex COMMD ring
Method: EM (single particle) / Resolution: 2.9 Å

17341

8p0x

EMDB-17341, PDB-8p0x:
Structure of the human Commander complex Retriever Subcomplex
Method: EM (single particle) / Resolution: 7.5 Å

EMDB-17342: Human Commander complex (native)
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsUNKNOWN FUNCTION / Coiled-coil / DENND domain / alpha solenoid / calponin homology / COMMD fold / calponin homology fold / pseudo-C5 symmetry / arrestin fold / phosphoesterase fold / complex

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