8p0v
From Proteopedia
Structure of the human Commander complex coiled coils, DENND10 and partial Retriever subcomplex
Structural highlights
FunctionDEN10_HUMAN Guanine nucleotide exchange factor (GEF) regulating homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion, possibly through activating Rab proteins such as RAB27A and RAB27B. Seems to promote the exchange of GDP to GTP, converting inactive GDP-bound RAB27A and RAB27B into their active GTP-bound form.[1] Publication Abstract from PubMedThe 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. Structure and interactions of the endogenous human Commander complex.,Laulumaa S, Kumpula EP, Huiskonen JT, Varjosalo M Nat Struct Mol Biol. 2024 Jun;31(6):925-938. doi: 10.1038/s41594-024-01246-1. , Epub 2024 Mar 8. PMID:38459129[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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