Crystal structure of COMMD7-COMMD9-COMMD5-COMMD10 tetramerCrystal structure of COMMD7-COMMD9-COMMD5-COMMD10 tetramer

Structural highlights

8esd is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.33Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

COMDA_HUMAN May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes (PubMed:21778237). May down-regulate activation of NF-kappa-B (PubMed:15799966).[1] [2]

Publication Abstract from PubMed

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.

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 Cell. 2023 May 11;186(10):2219-2237.e29. doi: 10.1016/j.cell.2023.04.003. PMID:37172566[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Burstein E, Hoberg JE, Wilkinson AS, Rumble JM, Csomos RA, Komarck CM, Maine GN, Wilkinson JC, Mayo MW, Duckett CS. COMMD proteins, a novel family of structural and functional homologs of MURR1. J Biol Chem. 2005 Jun 10;280(23):22222-32. Epub 2005 Mar 30. PMID:15799966 doi:http://dx.doi.org/10.1074/jbc.M501928200
  2. Mao X, Gluck N, Chen B, Starokadomskyy P, Li H, Maine GN, Burstein E. COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein 1) binding. J Biol Chem. 2011 Sep 16;286(37):32355-65. PMID:21778237 doi:10.1074/jbc.M111.278408
  3. Healy MD, McNally KE, Butkovič 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. Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome. Cell. 2023 May 11;186(10):2219-2237.e29. PMID:37172566 doi:10.1016/j.cell.2023.04.003

8esd, resolution 3.33Å

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