4LJQ

Crystal structure of the catalytic core of E3 ligase HOIP

4LJQ の概要

• エントリーDOI: 10.2210/pdb4ljq/pdb
• 関連するPDBエントリー: 4LJO 4LJP
• 分子名称: E3 ubiquitin-protein ligase RNF31, ZINC ION (3 entities in total)
• 機能のキーワード: rnf31, zibra, ring domain, zinc finger, ibr domain, rbr ligase, e3 ligase, ligase, ubiquitin, hoil-1, sharpin
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): Q96EP0
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 102138.75

構造登録者

Stieglitz, B.,Rana, R.R.,Koliopoulos, M.G.,Morris-Davies, A.C.,Christodoulou, E.,Howell, S.,Brown, N.R.,Rittinger, K. (登録日: 2013-07-05, 公開日: 2013-10-16, 最終更新日: 2024-11-06)

主引用文献

Stieglitz, B.,Rana, R.R.,Koliopoulos, M.G.,Morris-Davies, A.C.,Schaeffer, V.,Christodoulou, E.,Howell, S.,Brown, N.R.,Dikic, I.,Rittinger, K.
Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP.
Nature, 503:422-426, 2013

PubMed Abstract: Linear ubiquitin chains are important regulators of cellular signalling pathways that control innate immunity and inflammation through nuclear factor (NF)-κB activation and protection against tumour necrosis factor-α-induced apoptosis. They are synthesized by HOIP, which belongs to the RBR (RING-between-RING) family of E3 ligases and is the catalytic component of LUBAC (linear ubiquitin chain assembly complex), a multisubunit E3 ligase. RBR family members act as RING/HECT hybrids, employing RING1 to recognize ubiquitin-loaded E2 while a conserved cysteine in RING2 subsequently forms a thioester intermediate with the transferred or 'donor' ubiquitin. Here we report the crystal structure of the catalytic core of HOIP in its apo form and in complex with ubiquitin. The carboxy-terminal portion of HOIP adopts a novel fold that, together with a zinc-finger, forms a ubiquitin-binding platform that orients the acceptor ubiquitin and positions its α-amino group for nucleophilic attack on the E3∼ubiquitin thioester. The C-terminal tail of a second ubiquitin molecule is located in close proximity to the catalytic cysteine, providing a unique snapshot of the ubiquitin transfer complex containing both donor and acceptor ubiquitin. These interactions are required for activation of the NF-κB pathway in vivo, and they explain the determinants of linear ubiquitin chain specificity by LUBAC.

PubMed: 24141947
DOI: 10.1038/nature12638

実験手法

X-RAY DIFFRACTION (2.45 Å)