EMD-28825
Human CCC complex
EMD-28825
Single-particle3.12 Å
![EMD-28825](https://www.ebi.ac.uk/emdb/images/entry/EMD-28825/400_28825.gif)
Map released: 24/05/2023
Last modified: 19/06/2024
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
Sample: Human CCC complex
Fitted models: 8f2r (Avg. Q-score: 0.381)
Deposition Authors: Healy MD
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Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome.
Healy MD
,
McNally KE
,
Butkovic R
,
Chilton M,
Kato K,
Sacharz J,
McConville C,
Moody ERR
,
Shaw S,
Planelles-Herrero VJ
,
Yadav SKN,
Ross J,
Borucu U,
Palmer CS
,
Chen KE
,
Croll TI,
Hall RJ
,
Caruana NJ,
Ghai R,
Nguyen THD,
Heesom KJ,
Saitoh S,
Berger I,
Schaffitzel C,
Williams TA
,
Stroud DA
,
Derivery E,
Collins BM
,
Cullen PJ
(2023) Cell , 186 , 2219 - 2237.e29
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(2023) Cell , 186 , 2219 - 2237.e29
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.
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.