3OJ3
Crystal structure of the A20 ZnF4 and ubiquitin complex
Summary for 3OJ3
Entry DOI | 10.2210/pdb3oj3/pdb |
Related | 3OJ4 |
Descriptor | Ubiquitin, Tumor necrosis factor alpha-induced protein 3, ZINC ION, ... (4 entities in total) |
Functional Keywords | ubiquitin, zinc finger, zinc ion, protein binding-hydrolase complex, protein binding/hydrolase |
Biological source | Homo sapiens (human) More |
Total number of polymer chains | 16 |
Total formula weight | 114740.82 |
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-KB Signaling Mol.Cell, 40:548-557, 2010 Cited by 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: 21095585DOI: 10.1016/j.molcel.2010.10.009 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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