EMD-28825

Single-particle
3.12 Å
EMD-28825 Deposition: 08/11/2022
Map released: 24/05/2023
Last modified: 19/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-28825

Human CCC complex

EMD-28825

Single-particle
3.12 Å
EMD-28825 Deposition: 08/11/2022
Map released: 24/05/2023
Last modified: 19/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Human CCC complex
Fitted models: 8f2r (Avg. Q-score: 0.381)

Deposition Authors: Healy MD , McNally KE , Butkovic R , Chilton M, Kato K, Sacharz J, McConville C, Moody ERR , Shaw S, Planelles-Herrero VJ , Kadapalakere SY, Ross J, Borucu U, Palmer CS , Chen K, Croll TI, Hall RJ , Caruana NJ, Ghai R, Nguyen THD, Heesom KJ, Saitoh S, Berger I, Berger-Schaffitzel C, Williams TA , Stroud DA , Derivery E, Collins BM , Cullen PJ
Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome.
PUBMED: 37172566
DOI: doi:10.1016/j.cell.2023.04.003
ISSN: 1097-4172
Abstract:
The Commander complex is required for endosomal recycling of diverse transmembrane cargos and is mutated in Ritscher-Schinzel syndrome. It comprises two sub-assemblies: Retriever composed of VPS35L, VPS26C, and VPS29; and the CCC complex which contains twelve subunits: COMMD1-COMMD10 and the coiled-coil domain-containing (CCDC) proteins CCDC22 and CCDC93. Combining X-ray crystallography, electron cryomicroscopy, and in silico predictions, we have assembled a complete structural model of Commander. Retriever is distantly related to the endosomal Retromer complex but has unique features preventing the shared VPS29 subunit from interacting with Retromer-associated factors. The COMMD proteins form a distinctive hetero-decameric ring stabilized by extensive interactions with CCDC22 and CCDC93. These adopt a coiled-coil structure that connects the CCC and Retriever assemblies and recruits a 16th subunit, DENND10, to form the complete Commander complex. The structure allows mapping of disease-causing mutations and reveals the molecular features required for the function of this evolutionarily conserved trafficking machinery.