Crossref journal-article
Portland Press Ltd.
Biochemical Journal (288)
Abstract

The NF-κB (nuclear factor κB) regulator A20 antagonises IKK [IκB (inhibitor of κB) kinase] activation by modulating Lys63-linked polyubiquitination of cytokine-receptor-associated factors including TRAF2/6 (tumour-necrosis-factor-receptor-associated factor 2/6) and RIP1 (receptor-interacting protein 1). In the present paper we describe the crystal structure of the N-terminal OTU (ovarian tumour) deubiquitinase domain of A20, which differs from other deubiquitinases but shares the minimal catalytic core with otubain-2. Analysis of conserved surface regions allows prediction of ubiquitin-binding sites for the proximal and distal ubiquitin molecules. Structural and biochemical analysis suggests a novel architecture of the catalytic triad, which might be present in a subset of OTU domains including Cezanne and TRABID (TRAF-binding domain). Biochemical analysis shows a preference of the isolated A20 OTU domain for Lys48-linked tetraubiquitin in vitro suggesting that additional specificity factors might be required for the physiological function of A20 in cells.

Bibliography

Komander, D., & Barford, D. (2007). Structure of the A20 OTU domain and mechanistic insights into deubiquitination. Biochemical Journal, 409(1), 77–85.

Authors 2
  1. David Komander (first)
  2. David Barford (additional)
References 33 Referenced 160
  1. 10.1101/gad.1228704 / Genes Dev. / Signaling to NF-κB by Hayden (2004)
  2. 10.1038/nrm2083 / Nat. Rev. / Integrating cell-signalling pathways with NF-κB and IKK function by Perkins (2007)
  3. 10.1016/S0021-9258(18)77165-2 / J. Biol. Chem. / The A20 cDNA induced by tumor necrosis factor α encodes a novel type of zinc finger protein by Opipari (1990)
  4. 10.1016/S0006-2952(00)00404-4 / Biochem. Pharmacol. / A20 and A20-binding proteins as cellular inhibitors of nuclear factor-κB-dependent gene expression and apoptosis by Beyaert (2000)
  5. 10.1016/j.tibs.2004.11.001 / Trends Biochem. Sci. / A20 inhibits NF-κB activation by dual ubiquitin-editing functions by Heyninck (2005)
  6. 10.1126/science.289.5488.2350 / Science / Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice by Lee (2000)
  7. 10.1038/ni1110 / Nat. Immunol. / The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses by Boone (2004)
  8. 10.1038/nature02794 / Nature / De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling by Wertz (2004)
  9. 10.1038/sj.onc.1210413 / Oncogene / Ubiquitin-mediated activation of TAK1 and IKK by Adhikari (2007)
  10. 10.1038/ncb0805-758 / Nat. Cell Biol. / Ubiquitin signalling in the NF-κB pathway by Chen (2005)
  11. 10.1017/S1462399405009415 / Expert Rev. Mol. Med. / Regulation of pro-inflammatory signalling networks by ubiquitin: identification of novel targets for anti-inflammatory drugs by Evans (2005)
  12. 10.1016/j.molcel.2006.05.002 / Mol. Cell / If the prophet does not come to the mountain: dynamics of signaling complexes in NF-κB activation by Kovalenko (2006)
  13. 10.1038/nsmb1064 / Nat. Struct. Mol. Biol. / Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5 by Lee (2006)
  14. 10.1016/j.cell.2006.02.020 / Cell / Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin by Penengo (2006)
  15. 10.1016/0014-5793(96)00283-9 / FEBS Lett. / A20, an inhibitor of cell death, self-associates by its zinc finger domain by De Valck (1996)
  16. 10.1074/jbc.M100048200 / J. Biol. Chem. / Identification of a novel A20-binding inhibitor of nuclear factor-κB activation termed ABIN-2 by Van Huffel (2001)
  17. 10.1038/sj.onc.1202787 / Oncogene / The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases by De Valck (1999)
  18. 10.1042/bj20031377 / Biochem. J. / Zinc-finger protein A20, a regulator of inflammation and cell survival, has de-ubiquitinating activity by Evans (2004)
  19. 10.1074/jbc.M301863200 / J. Biol. Chem. / A novel type of deubiquitinating enzyme by Evans (2003)
  20. 10.1038/sj.embor.7400201 / EMBO Rep. / Crystal structure of human otubain 2 by Nanao (2004)
  21. 10.1107/S0021889804018047 / J. Appl. Cryst. / Hkl2map: a graphical user interface for macromolecular phasing with shelx programs by Pape (2004)
  22. 10.1107/S0907444903017694 / Acta Crystallogr. Sect. D Biol. Crystallogr. / Generation, representation and flow of phase information in structure determination: recent developments in and around SHARP 2.0 by Bricogne (2003)
  23. 10.1107/S0907444997011980 / Acta Crystallogr. Sect. D Biol. Crystallogr. / Miscellaneous algorithms for density modification by Cowtan (1998)
  24. 10.1107/S0907444904019158 / Acta Crystallogr. Sect. D Biol. Crystallogr. / Coot: model-building tools for molecular graphics by Emsley (2004)
  25. 10.1107/S0907444902016657 / Acta Crystallogr. Sect. D Biol. Crystallogr. / PHENIX: building new software for automated crystallographic structure determination by Adams (2002)
  26. 10.1006/jmbi.1993.1489 / J. Mol. Biol. / Protein structure comparison by alignment of distance matrices by Holm (1993)
  27. 10.1093/nar/gkj063 / Nucleic Acids Res. / The PROSITE database by Hulo (2006)
  28. 10.1016/j.bbamcr.2004.10.003 / Biochim. Biophys. Acta / Mechanism and function of deubiquitinating enzymes by Amerik (2004)
  29. 10.1016/j.cell.2005.11.007 / Cell / A genomic and functional inventory of deubiquitinating enzymes by Nijman (2005)
  30. 10.1016/S0092-8674(02)01199-6 / Cell / Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde by Hu (2002)
  31. 10.1093/emboj/18.14.3877 / EMBO J. / Structural basis for the specificity of ubiquitin C-terminal hydrolases by Johnston (1999)
  32. 10.1042/bj3570617 / Biochem. J. / Isolation and characterization of two novel A20-like proteins by Evans (2001)
  33. 10.1083/jcb.200401010 / J. Cell. Biol. / VCIP135 acts as a deubiquitinating enzyme during p97-p47-mediated reassembly of mitotic Golgi fragments by Wang (2004)
Dates
Type When
Created 17 years, 8 months ago (Dec. 13, 2007, 6:17 a.m.)
Deposited 3 years, 9 months ago (Nov. 22, 2021, 10:53 a.m.)
Indexed 4 months, 3 weeks ago (April 11, 2025, 8:26 p.m.)
Issued 17 years, 8 months ago (Dec. 11, 2007)
Published 17 years, 8 months ago (Dec. 11, 2007)
Published Online 17 years, 8 months ago (Dec. 11, 2007)
Published Print 17 years, 8 months ago (Jan. 1, 2008)
Funders 0

None

@article{Komander_2007, title={Structure of the A20 OTU domain and mechanistic insights into deubiquitination}, volume={409}, ISSN={1470-8728}, url={http://dx.doi.org/10.1042/bj20071399}, DOI={10.1042/bj20071399}, number={1}, journal={Biochemical Journal}, publisher={Portland Press Ltd.}, author={Komander, David and Barford, David}, year={2007}, month=dec, pages={77–85} }