8BJA

Structure of the human UBR5 Dimer.

8BJA の概要

• エントリーDOI: 10.2210/pdb8bja/pdb
• EMDBエントリー: 16087
• 分子名称: E3 ubiquitin-protein ligase UBR5, ZINC ION (2 entities in total)
• 機能のキーワード: ubr5, e3 ligase, nuclear, degradation, ubiquitin, ligase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 626014.27

構造登録者

Hodakova, Z.,Grishkovskaya, I.,Haselbach, D. (登録日: 2022-11-03, 公開日: 2023-07-12, 最終更新日: 2023-09-06)

主引用文献

Hodakova, Z.,Grishkovskaya, I.,Brunner, H.L.,Bolhuis, D.L.,Belacic, K.,Schleiffer, A.,Kotisch, H.,Brown, N.G.,Haselbach, D.
Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5.
Embo J., 42:e113348-e113348, 2023

PubMed Abstract: UBR5 is a nuclear E3 ligase that ubiquitinates a vast range of substrates for proteasomal degradation. This HECT domain-containing ubiquitin ligase has recently been identified as an important regulator of oncogenes, e.g., MYC, but little is known about its structure or mechanisms of substrate engagement and ubiquitination. Here, we present the cryo-EM structure of human UBR5, revealing an α-solenoid scaffold with numerous protein-protein interacting motifs, assembled into an antiparallel dimer that adopts further oligomeric states. Using cryo-EM processing tools, we observe the dynamic nature of the UBR5 catalytic domain, which we postulate is important for its enzymatic activity. We characterise the proteasomal nuclear import factor AKIRIN2 as an interacting protein and propose UBR5 as an efficient ubiquitin chain elongator. This preference for ubiquitinated substrates and several distinct domains for protein-protein interactions may explain how UBR5 is linked to several different signalling pathways and cancers. Together, our data expand on the limited knowledge of the structure and function of HECT E3 ligases.

PubMed: 37409633
DOI: 10.15252/embj.2022113348

実験手法

ELECTRON MICROSCOPY (3 Å)