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Structure of the A20 OTU domain and mechanistic insights into deubiquitination

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Komander, David, Barford, David·2008·Biochemical Journal

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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Metadata

Authors
Komander, D., & Barford, D.
Venue
Biochemical Journal
Published
2007-12-11
Volume
409
Issue
1
Pages
77-85
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
OpenAlex
W2095803950
Cited by
170
References
6
FWCI
4.43
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Structure of the A20 OTU domain and mechanistic insights into deubiquitination. https://app.cochat.ai/papers/10.1042/bj20071399
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Komander, D., & Barford, D. (2008). Structure of the A20 OTU domain and mechanistic insights into deubiquitination. Biochemical Journal. https://doi.org/10.1042/bj20071399

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