6TAX

Mouse RNF213 wild type protein

6TAX の概要

• エントリーDOI: 10.2210/pdb6tax/pdb
• 関連するPDBエントリー: 6TAY
• EMDBエントリー: 10429
• 分子名称: RNF213,E3 ubiquitin-protein ligase RNF213,E3 ubiquitin-protein ligase RNF213, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: rnf213, e3 ligase, aaa-protein, signaling protein
• 由来する生物種: Mus musculus (House mouse); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 528340.62

構造登録者

Ahel, J.,Meinhart, A.,Haselbach, D.,Clausen, T. (登録日: 2019-10-31, 公開日: 2020-07-01, 最終更新日: 2024-11-13)

主引用文献

Ahel, J.,Lehner, A.,Vogel, A.,Schleiffer, A.,Meinhart, A.,Haselbach, D.,Clausen, T.
Moyamoya disease factor RNF213 is a giant E3 ligase with a dynein-like core and a distinct ubiquitin-transfer mechanism.
Elife, 9:-, 2020

PubMed Abstract: RNF213 is the major susceptibility factor for Moyamoya disease, a progressive cerebrovascular disorder that often leads to brain stroke in adults and children. Characterization of disease-associated mutations has been complicated by the enormous size of RNF213. Here, we present the cryo-EM structure of mouse RNF213. The structure reveals the intricate fold of the 584 kDa protein, comprising an N-terminal stalk, a dynein-like core with six ATPase units, and a multidomain E3 module. Collaboration with UbcH7, a cysteine-reactive E2, points to an unexplored ubiquitin-transfer mechanism that proceeds in a RING-independent manner. Moreover, we show that pathologic MMD mutations cluster in the composite E3 domain, likely interfering with substrate ubiquitination. In conclusion, the structure of RNF213 uncovers a distinct type of an E3 enzyme, highlighting the growing mechanistic diversity in ubiquitination cascades. Our results also provide the molecular framework for investigating the emerging role of RNF213 in lipid metabolism, hypoxia, and angiogenesis.

PubMed: 32573437
DOI: 10.7554/eLife.56185

実験手法

ELECTRON MICROSCOPY (3.2 Å)