Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Helsinki, Finland.
Nat Struct Mol Biol. 2024 Jun;31(6):925-938. doi: 10.1038/s41594-024-01246-1. Epub 2024 Mar 8.
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.
指挥官复合物（Commander complex）是由 16 种蛋白组成的复合物，在细胞内稳态、细胞周期和免疫反应中发挥多种作用。它由铜代谢 Murr1 结构域蛋白（COMMD1-10）、卷曲螺旋结构域蛋白（CCDC22 和 CCDC93）、DENND10 和 Retriever 亚基复合物（VPS26C、VPS29 和 VPS35L）组成，这些蛋白在体内广泛表达，与多种疾病相关。在这里，我们通过低温电子显微镜和基于质谱的蛋白质组学方法报告了内源性人源指挥官复合物的结构和关键相互作用。该复合物由稳定的 COMMD1-10 核心和包含 DENND10 和 Retriever 的效应器组成，由 CCDC22 和 CCDC93 构成支架。我们确定了指挥官复合物的组成，并揭示了主要的相互作用界面。这些发现阐明了其在细胞内运输中的作用，并揭示了与纤毛组装、中心体和中心粒功能的强烈关联。
