8ESD

Crystal structure of COMMD7-COMMD9-COMMD5-COMMD10 tetramer

Summary for 8ESD

• Entry DOI: 10.2210/pdb8esd/pdb
• Descriptor: COMM domain-containing protein 10, COMM domain-containing protein 9, COMM domain-containing protein 5, ... (4 entities in total)
• Functional Keywords: complex, commander, retriever, commd5, commd7, commd9, commd10, commd, endocytosis
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 60095.01

Authors

Healy, M.D.,Collins, B.M. (deposition date: 2022-10-13, release date: 2023-05-24, Last modification date: 2023-10-25)

Primary citation

Healy, M.D.,McNally, K.E.,Butkovic, R.,Chilton, M.,Kato, K.,Sacharz, J.,McConville, C.,Moody, E.R.R.,Shaw, S.,Planelles-Herrero, V.J.,Yadav, S.K.N.,Ross, J.,Borucu, U.,Palmer, C.S.,Chen, K.E.,Croll, T.I.,Hall, R.J.,Caruana, N.J.,Ghai, R.,Nguyen, T.H.D.,Heesom, K.J.,Saitoh, S.,Berger, I.,Schaffitzel, C.,Williams, T.A.,Stroud, D.A.,Derivery, E.,Collins, B.M.,Cullen, P.J.
Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome.
Cell, 186:2219-2237.e29, 2023

PubMed 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.

PubMed: 37172566
DOI: 10.1016/j.cell.2023.04.003

Experimental method

X-RAY DIFFRACTION (3.33 Å)