Cell · 2023
Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Healy Michael D, McNally Kerrie E, Butkovič Rebeka, Chilton Molly, Kato Kohji, Sacharz Joanna, McConville Calum, Moody Edmund R R, Shaw Shrestha, Planelles-Herrero Vicente J, Yadav Sathish K N, Ross Jennifer, Borucu Ufuk, Palmer Catherine S, Chen Kai-En, Croll Tristan I, Hall Ryan J, Caruana Nikeisha J, Ghai Rajesh, Nguyen Thi H D, Heesom Kate J, Saitoh Shinji, Berger Imre, Schaffitzel Christiane, Williams Tom A, Stroud David A, Derivery Emmanuel, Collins Brett M, Cullen Peter J
Аннотация
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.