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.
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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) |
@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} }