3OJ4

Crystal structure of the A20 ZnF4, ubiquitin and UbcH5A complex

Summary for 3OJ4

• Entry DOI: 10.2210/pdb3oj4/pdb
• Related: 3OJ3
• Descriptor: Ubiquitin-conjugating enzyme E2 D1, Ubiquitin, Tumor necrosis factor alpha-induced protein 3, ... (4 entities in total)
• Functional Keywords: ubiquitin, zinc finger, ubiquitin conjugating enzyme, zinc ion, ligase-protein binding complex, ligase/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : P51668; Ubiquitin: Cytoplasm : P0CG47; Cytoplasm. A20p50: Cytoplasm: P21580
• Total number of polymer chains: 6
• Total formula weight: 63240.72

Authors

Bosanac, I.,Hymowitz, S.G. (deposition date: 2010-08-20, release date: 2010-12-08, Last modification date: 2023-09-06)

Primary citation

Bosanac, I.,Wertz, I.E.,Pan, B.,Yu, C.,Kusam, S.,Lam, C.,Phu, L.,Phung, Q.,Maurer, B.,Arnott, D.,Kirkpatrick, D.S.,Dixit, V.M.,Hymowitz, S.G.
Ubiquitin Binding to A20 ZnF4 Is Required for Modulation of NF-κB Signaling
Mol.Cell, 40:548-557, 2010

PubMed Abstract: Inactivating mutations in the ubiquitin (Ub) editing protein A20 promote persistent nuclear factor (NF)-κB signaling and are genetically linked to inflammatory diseases and hematologic cancers. A20 tightly regulates NF-κB signaling by acting as an Ub editor, removing K63-linked Ub chains and mediating addition of Ub chains that target substrates for degradation. However, a precise molecular understanding of how A20 modulates this pathway remains elusive. Here, using structural analysis, domain mapping, and functional assays, we show that A20 zinc finger 4 (ZnF4) does not directly interact with E2 enzymes but instead can bind mono-Ub and K63-linked poly-Ub. Mutations to the A20 ZnF4 Ub-binding surface result in decreased A20-mediated ubiquitination and impaired regulation of NF-κB signaling. Collectively, our studies illuminate the mechanistically distinct but biologically interdependent activities of the A20 ZnF and ovarian tumor (OTU) domains that are inherent to the Ub editing process and, ultimately, to regulation of NF-κB signaling.

PubMed: 21095585
DOI: 10.1016/j.molcel.2010.10.009

Experimental method

X-RAY DIFFRACTION (3.4 Å)