8f2r

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Human CCC complexHuman CCC complex

Structural highlights

8f2r is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

COMD1_HUMAN Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity. Down-regulates SOD1 activity by interfering with its homodimerization. Plays a role in copper ion homeostasis. Can bind one copper ion per monomer. May function to facilitate biliary copper excretion within hepatocytes.[1] [2] [3] [4] [5] [6] [7]

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[8]

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

References

  1. ↑ Burstein E, Ganesh L, Dick RD, van De Sluis B, Wilkinson JC, Klomp LW, Wijmenga C, Brewer GJ, Nabel GJ, Duckett CS. A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J. 2004 Jan 14;23(1):244-54. Epub 2003 Dec 18. PMID:14685266 doi:10.1038/sj.emboj.7600031
  2. ↑ 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
  3. ↑ de Bie P, van de Sluis B, Burstein E, Duran KJ, Berger R, Duckett CS, Wijmenga C, Klomp LW. Characterization of COMMD protein-protein interactions in NF-kappaB signalling. Biochem J. 2006 Aug 15;398(1):63-71. PMID:16573520 doi:http://dx.doi.org/BJ20051664
  4. ↑ Narindrasorasak S, Kulkarni P, Deschamps P, She YM, Sarkar B. Characterization and copper binding properties of human COMMD1 (MURR1). Biochemistry. 2007 Mar 20;46(11):3116-28. Epub 2007 Feb 20. PMID:17309234 doi:http://dx.doi.org/10.1021/bi0620656
  5. ↑ Maine GN, Mao X, Komarck CM, Burstein E. COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase. EMBO J. 2007 Jan 24;26(2):436-47. Epub 2006 Dec 21. PMID:17183367 doi:http://dx.doi.org/10.1038/sj.emboj.7601489
  6. ↑ Thoms HC, Loveridge CJ, Simpson J, Clipson A, Reinhardt K, Dunlop MG, Stark LA. Nucleolar targeting of RelA(p65) is regulated by COMMD1-dependent ubiquitination. Cancer Res. 2010 Jan 1;70(1):139-49. doi: 10.1158/0008-5472.CAN-09-1397. PMID:20048074 doi:http://dx.doi.org/10.1158/0008-5472.CAN-09-1397
  7. ↑ Vonk WI, Wijmenga C, Berger R, van de Sluis B, Klomp LW. Cu,Zn superoxide dismutase maturation and activity are regulated by COMMD1. J Biol Chem. 2010 Sep 10;285(37):28991-9000. doi: 10.1074/jbc.M110.101477. Epub, 2010 Jul 1. PMID:20595380 doi:http://dx.doi.org/10.1074/jbc.M110.101477
  8. ↑ 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

8f2r, resolution 3.12Å

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