3EB5

Structure of the cIAP2 RING domain

3EB5 の概要

• エントリーDOI: 10.2210/pdb3eb5/pdb
• 関連するPDBエントリー: 3EB6
• 分子名称: Baculoviral IAP repeat-containing protein 3, ZINC ION, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: ring domain, apoptosis, metal-binding, zinc-finger
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm (Potential): Q13489
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8392.48

構造登録者

Mace, P.D.,Linke, K.,Smith, C.A.,Day, C.L. (登録日: 2008-08-27, 公開日: 2008-09-09, 最終更新日: 2024-02-21)

主引用文献

Mace, P.D.,Linke, K.,Feltham, R.,Schumacher, F.R.,Smith, C.A.,Vaux, D.L.,Silke, J.,Day, C.L.
Structures of the cIAP2 RING domain reveal conformational changes associated with ubiquitin-conjugating enzyme (E2) recruitment.
J.Biol.Chem., 283:31633-31640, 2008

PubMed Abstract: Inhibitor of apoptosis (IAP) proteins are key negative regulators of cell death that are highly expressed in many cancers. Cell death caused by antagonists that bind to IAP proteins is associated with their ubiquitylation and degradation. The RING domain at the C terminus of IAP proteins is pivotal. Here we report the crystal structures of the cIAP2 RING domain homodimer alone, and bound to the ubiquitin-conjugating (E2) enzyme UbcH5b. These structures show that small changes in the RING domain accompany E2 binding. By mutating residues at the E2-binding surface, we show that autoubiquitylation is required for regulation of IAP abundance. Dimer formation is also critical, and mutation of a single C-terminal residue abrogated dimer formation and E3 ligase activity was diminished. We further demonstrate that disruption of E2 binding, or dimerization, stabilizes IAP proteins against IAP antagonists in vivo.

PubMed: 18784070
DOI: 10.1074/jbc.M804753200

実験手法

X-RAY DIFFRACTION (2 Å)