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.
Research Article| December 11 2007
Structure of the A20 OTU domain and mechanistic insights into deubiquitination
David Komander 1
1Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, U.K.
1To whom correspondence should be addressed (email email@example.com).
Search for other works by this author on:
- Views Icon Views
- Share Icon Share
- Cite Icon Cite
David Komander, David Barford; Structure of the A20 OTU domain and mechanistic insights into deubiquitination. Biochem J 1 January 2008; 409 (1): 77–85. doi: https://doi.org/10.1042/BJ20071399
Download citation file: