9M7O

Cryo-EM structure of Ufd2/Ubc4-ub complex with K29triUb(monomeric conformation)

9M7O の概要

• エントリーDOI: 10.2210/pdb9m7o/pdb
• EMDBエントリー: 62355
• 分子名称: Ubiquitin-conjugating enzyme E2 4, Polyubiquitin-C, Ubiquitin, ... (5 entities in total)
• 機能のキーワード: e4 enzyme, ufd2, branch ub chains, ligase
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (brewer's yeast); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 152334.67

構造登録者

Tong, Z.B.,Liu, L. (登録日: 2025-03-10, 公開日: 2025-07-30, 最終更新日: 2026-02-18)

主引用文献

Tong, Z.,Wu, X.,Cai, H.,Wu, S.,Zhang, T.,Deng, Z.,Xu, Z.,Yuan, R.,Ai, H.,Liu, L.,Pan, M.
Structural basis for E4 enzyme Ufd2-catalyzed K48/K29 branched ubiquitin chains.
Nat.Chem.Biol., 22:239-248, 2026

PubMed Abstract: E4 enzymes amplify and remodel ubiquitin chain signals beyond the conventional E1-E2-E3 cascade. The first identified E4 enzyme Ufd2 preferentially catalyzes K48/K29 branched ubiquitin chains, yet the structural mechanism remains unknown. Here, we combined chemical biology and cryo-electron microscopy to visualize stable intermediates in Ufd2 loading ubiquitin at K48 of proximal ubiquitin on K29-linked di- and triubiquitin. Our data reveal that the core region of Ufd2 functions as an unprecedented K29 diubiquitin binding domain, interacting extensively with proximal and distal ubiquitin, which orients the K48 site of proximal ubiquitin toward the active site of Ubc4, facilitating K48/K29 branched ubiquitin chain formation. We also identified a unique dimeric conformation where dimerized Ufd2 and Ubc4 stabilize each other's distal ubiquitin during branching on K29 triubiquitin. Our findings provide mechanistic insights into the assembly of K48/K29 branched ubiquitin chains by the E4 enzyme Ufd2 and highlight the spatial cooperation among multiple pairs of ubiquitin-related enzymes on longer ubiquitin chains.

PubMed: 40817136
DOI: 10.1038/s41589-025-01985-2

実験手法

ELECTRON MICROSCOPY (4.14 Å)