5TTE

Crystal Structure of an RBR E3 ubiquitin ligase in complex with an E2-Ub thioester intermediate mimic

5TTE の概要

• エントリーDOI: 10.2210/pdb5tte/pdb
• 分子名称: E3 ubiquitin-protein ligase ARIH1, Ubiquitin-conjugating enzyme E2 L3, ubiquitin, ... (4 entities in total)
• 機能のキーワード: rbr e3 ubiquitin ligase, e2, complex, transthioloation, transferase, ligase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 94078.82

構造登録者

Yuan, L.,Lv, Z.,Olsen, S.K. (登録日: 2016-11-03, 公開日: 2017-08-23, 最終更新日: 2024-10-30)

主引用文献

Yuan, L.,Lv, Z.,Atkison, J.H.,Olsen, S.K.
Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI.
Nat Commun, 8:211-211, 2017

PubMed Abstract: RING-in-between-RING (RBR) ubiquitin (Ub) E3 ligases function with Ub E2s through a RING/HECT hybrid mechanism to conjugate Ub to target proteins. Here, we report the crystal structure of the RBR E3, HHARI, in complex with a UbcH7 ~ Ub thioester mimetic which reveals the molecular basis for the specificity of this cognate E2/RBR E3 pair. The structure also reveals mechanistically important conformational changes in the RING1 and UBA-like domains of HHARI that accompany UbcH7 ~ Ub binding and provides a molecular basis by which HHARI recruits E2 ~ Ub in an 'open' conformation. In addition to optimally functioning with an E2 that solely performs transthiolation, our data suggests that HHARI prevents spurious discharge of Ub from E2 to lysine residues by: (1) harboring structural elements that block E2 ~ Ub from adopting a 'closed' conformation and (2) participating in contacts to ubiquitin that promote an open E2 ~ Ub conformation.HHARI is a RING-in-between-RING (RBR) ubiquitin (Ub) E3 ligase. Here the authors present the crystal structure of HHARI with the UbcH7 ~ Ub thioester intermediate mimetic, which reveals that HHARI binds this E2 ~ Ub in an open conformation and explains the specificity of this cognate RBR E3/E2 pair.

PubMed: 28790309
DOI: 10.1038/s41467-017-00272-6

実験手法

X-RAY DIFFRACTION (3.501 Å)