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Unravelling the Molecular Architecture of the Commander Trafficking Machinery [IRB Research Nodes Seminar]

10 Apr 24

Speaker: Dr. Michael Healy 

Postdoctoral Research Fellow, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia




Hosts: Dr. Antonio Zorzano & Dr. María J. Macías, Group Leaders - IRB Barcelona 

Node: Chemical & Structural Biology / Preclinical Models of Disease

Date: Wednesday 10 April 2024, 12.00h

Place: Auditorium Room


IMPORTANT: For attendees outside the PCB community you must register at least 24h before the seminar.



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