Proteopedia

Cullin

Cullins are hydrophobic scaffold proteins for E3 ubiquitin ligases. They combine with ring box proteins (RBX) to form the CRL complex.[1] The CRL complex is essential in targeting proteins to ubiquitin-mediated destruction. Cullin-1 to 7 are part of the multi-subunit ubiquitin complex. Conjugation of cullin to NEDD8 modulates the activation of the CRL.

  • Cullin-1 is part of the SCF (Skp-cullin-F-box containing) complex which catalyzes the ubiquitination of proteins.[2]
  • Cullin-2 is part of the ECS (Elongin-cullin-SOCS-box) complex.[3]
  • Cullin-3 is part of the BTB-Cul3 complex.[4]
  • Cullin-4A and 4B regulate various processes like DNA repair, chromatin remodeling and mitotic cell cycle.[5]
  • Cullin-5 inhibits cellular proliferation.[6]
  • Cullin-7 is a core component of a complex which mediates ubiquitination of target proteins.[7]

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.(PDB code 1ldj)

3D Structures of cullin

Cullin 3D structures


Human cullin-1 (cyan) complex with ring box protein 1 (green) and Zn+2 ion (grey) (PDB code 1ldj)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Petroski MD, Deshaies RJ. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol. 2005 Jan;6(1):9-20. PMID:15688063 doi:http://dx.doi.org/10.1038/nrm1547
  2. ↑ Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature. 2002 Apr 18;416(6882):703-9. PMID:11961546 doi:http://dx.doi.org/10.1038/416703a
  3. ↑ Nguyen HC, Yang H, Fribourgh JL, Wolfe LS, Xiong Y. Insights into Cullin-RING E3 Ubiquitin Ligase Recruitment: Structure of the VHL-EloBC-Cul2 Complex. Structure. 2015 Feb 3. pii: S0969-2126(14)00423-7. doi:, 10.1016/j.str.2014.12.014. PMID:25661653 doi:http://dx.doi.org/10.1016/j.str.2014.12.014
  4. ↑ Canning P, Cooper CD, Krojer T, Murray JW, Pike AC, Chaikuad A, Keates T, Thangaratnarajah C, Hojzan V, Marsden BD, Gileadi O, Knapp S, von Delft F, Bullock AN. Structural basis for Cul3 assembly with the BTB-Kelch family of E3 ubiquitin ligases. J Biol Chem. 2013 Jan 24. PMID:23349464 doi:http://dx.doi.org/10.1074/jbc.M112.437996
  5. ↑ Fischer ES, Scrima A, Bohm K, Matsumoto S, Lingaraju GM, Faty M, Yasuda T, Cavadini S, Wakasugi M, Hanaoka F, Iwai S, Gut H, Sugasawa K, Thoma NH. The Molecular Basis of CRL4(DDB2/CSA) Ubiquitin Ligase Architecture, Targeting, and Activation. Cell. 2011 Nov 23;147(5):1024-39. PMID:22118460 doi:10.1016/j.cell.2011.10.035
  6. ↑ Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA. Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell. 2008 Sep 19;134(6):995-1006. PMID:18805092 doi:http://dx.doi.org/10.1016/j.cell.2008.07.022
  7. ↑ Kaustov L, Lukin J, Lemak A, Duan S, Ho M, Doherty R, Penn LZ, Arrowsmith CH. The conserved CPH domains of Cul7 and PARC are protein-protein interaction modules that bind the tetramerization domain of p53. J Biol Chem. 2007 Apr 13;282(15):11300-7. Epub 2007 Feb 12. PMID:17298945 doi:10.1074/jbc.M611297200

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