4KBL

Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an Ariadne-family E3 and insights into ligation mechanism

4KBL の概要

• エントリーDOI: 10.2210/pdb4kbl/pdb
• 関連するPDBエントリー: 4KC9
• 分子名称: E3 ubiquitin-protein ligase ARIH1, ZINC ION (2 entities in total)
• 機能のキーワード: ring-ibr-ring, e3 ubiquitin ligase, ligase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9Y4X5
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 129468.71

構造登録者

Duda, D.M.,Olszewski, J.L.,Schulman, B.A. (登録日: 2013-04-23, 公開日: 2013-05-29, 最終更新日: 2024-02-28)

主引用文献

Duda, D.M.,Olszewski, J.L.,Schuermann, J.P.,Kurinov, I.,Miller, D.J.,Nourse, A.,Alpi, A.F.,Schulman, B.A.
Structure of HHARI, a RING-IBR-RING Ubiquitin Ligase: Autoinhibition of an Ariadne-Family E3 and Insights into Ligation Mechanism.
Structure, 21:1030-1041, 2013

PubMed Abstract: A distinct mechanism for ubiquitin (Ub) ligation has recently been proposed for the RING1-IBR-RING2 (RBR) family of E3s: an N-terminal RING1 domain recruits a thioester-linked intermediate complex between Ub and the E2 UbcH7, and a structurally distinct C-terminal RING2 domain displays a catalytic cysteine required for Ub ligation. To obtain insights into RBR E3s, we determined the crystal structure of the human homolog of Ariadne (HHARI), which reveals the individual RING1, IBR, and RING2 domains embedded in superdomains involving sequences specific to the Ariadne RBR subfamily. The central IBR is flanked on one side by RING1, which is exposed and binds UbcH7. On the other side, a C-terminal autoinhibitory "Ariadne domain" masks the RING2 active site. Insights into RBR E3 mechanisms are provided by structure-based mutations that indicate distinct steps of relief from autoinhibition, Ub transfer from E2 to HHARI, and ligation from the HHARI cysteine to a terminal acceptor.

PubMed: 23707686
DOI: 10.1016/j.str.2013.04.019

実験手法

X-RAY DIFFRACTION (3.3 Å)