3VUY

Crystal structure of A20 ZF7 in complex with linear tetraubiquitin

3VUY の概要

• エントリーDOI: 10.2210/pdb3vuy/pdb
• 関連するPDBエントリー: 3VUW 3VUX
• 分子名称: Polyubiquitin-C, Tumor necrosis factor alpha-induced protein 3, ZINC ION, ... (5 entities in total)
• 機能のキーワード: zinc finger, protein binding-metal binding protein complex, protein binding/metal binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm. A20p50: Cytoplasm: P0CG48; Ubiquitin: Cytoplasm (By similarity): P21580
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 37973.66

構造登録者

Nishimasu, H.,Ishitani, R.,Nureki, O. (登録日: 2012-07-09, 公開日: 2013-02-13, 最終更新日: 2024-03-20)

主引用文献

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

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: 23032187
DOI: 10.1038/emboj.2012.241

実験手法

X-RAY DIFFRACTION (1.981 Å)