3VUW
Crystal structure of A20 ZF7 in complex with linear ubiquitin, form I
Summary for 3VUW
Entry DOI | 10.2210/pdb3vuw/pdb |
Related | 3VUX 3VUY |
Descriptor | Polyubiquitin-C, Tumor necrosis factor alpha-induced protein 3, ZINC ION, ... (5 entities in total) |
Functional Keywords | zinc finger, cellular signaling, ubiquitination, protein binding-metal binding protein complex, protein binding/metal binding protein |
Biological source | Homo sapiens (human) More |
Cellular location | Cytoplasm. A20p50: Cytoplasm: P0CG48 Ubiquitin: Cytoplasm (By similarity): P21580 |
Total number of polymer chains | 6 |
Total formula weight | 37802.51 |
Authors | Nishimasu, H.,Ishitani, R.,Nureki, O. (deposition date: 2012-07-09, release date: 2013-02-13, Last modification date: 2024-03-20) |
Primary citation | Tokunaga, F.,Nishimasu, H.,Ishitani, R.,Goto, E.,Noguchi, T.,Mio, K.,Kamei, K.,Ma, A.,Iwai, K.,Nureki, O. Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-kappaB regulation Embo J., 31:3856-3870, 2012 Cited by PubMed Abstract: LUBAC (linear ubiquitin chain assembly complex) activates the canonical NF-κB pathway through linear polyubiquitination of NEMO (NF-κB essential modulator, also known as IKKγ) and RIP1. However, the regulatory mechanism of LUBAC-mediated NF-κB activation remains elusive. Here, we show that A20 suppresses LUBAC-mediated NF-κB activation by binding linear polyubiquitin via the C-terminal seventh zinc finger (ZF7), whereas CYLD suppresses it through deubiquitinase (DUB) activity. We determined the crystal structures of A20 ZF7 in complex with linear diubiquitin at 1.70-1.98 Å resolutions. The crystal structures revealed that A20 ZF7 simultaneously recognizes the Met1-linked proximal and distal ubiquitins, and that genetic mutations associated with B cell lymphomas map to the ubiquitin-binding sites. Our functional analysis indicated that the binding of A20 ZF7 to linear polyubiquitin contributes to the recruitment of A20 into a TNF receptor (TNFR) signalling complex containing LUBAC and IκB kinase (IKK), which results in NF-κB suppression. These findings provide new insight into the regulation of immune and inflammatory responses. PubMed: 23032187DOI: 10.1038/emboj.2012.241 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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