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-Structure paper
Title | Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome. |
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Journal, issue, pages | Cell, Vol. 186, Issue 10, Page 2219-2237.e29, Year 2023 |
Publish date | May 11, 2023 |
Authors | Michael D Healy / Kerrie E McNally / Rebeka Butkovič / Molly Chilton / Kohji Kato / Joanna Sacharz / Calum McConville / Edmund R R Moody / Shrestha Shaw / Vicente J Planelles-Herrero / Sathish K N Yadav / Jennifer Ross / Ufuk Borucu / Catherine S Palmer / Kai-En Chen / Tristan I Croll / Ryan J Hall / Nikeisha J Caruana / Rajesh Ghai / Thi H D Nguyen / Kate J Heesom / Shinji Saitoh / Imre Berger / Christiane Schaffitzel / Tom A Williams / David A Stroud / Emmanuel Derivery / Brett M Collins / Peter J Cullen / |
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, ...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. |
External links | Cell / PubMed:37172566 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.35 - 3.53 Å |
Structure data | EMDB-28825, PDB-8f2r: EMDB-28827, PDB-8f2u: PDB-8esd: PDB-8ese: |
Chemicals | ChemComp-HOH: |
Source |
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Keywords | ENDOCYTOSIS / Complex / Commander / Retriever / Commd5 / Commd7 / Commd9 / Commd10 / Commd / Vps29 / Vps35L / endosomal sorting / CCC complex |