Structure and interactions of the endogenous human Commander complex

Saara Laulumaa; Esa-Pekka Kumpula; Juha T Huiskonen; Markku Varjosalo

doi:10.1038/s41594-024-01246-1

Structure and interactions of the endogenous human Commander complex

Nat Struct Mol Biol. 2024 Mar 8. doi: 10.1038/s41594-024-01246-1. Online ahead of print.

Authors

Saara Laulumaa^#¹, Esa-Pekka Kumpula^#¹, Juha T Huiskonen², Markku Varjosalo³

Affiliations

¹ Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Helsinki, Finland.
² Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Helsinki, Finland. juha.huiskonen@helsinki.fi.
³ Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Helsinki, Finland. markku.varjosalo@helsinki.fi.

^# Contributed equally.

PMID: 38459129
DOI: 10.1038/s41594-024-01246-1

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.