6W9D

RNF12 RING domain in complex with a Ube2d2~Ub conjugate

6W9D の概要

• エントリーDOI: 10.2210/pdb6w9d/pdb
• 関連するPDBエントリー: 6W7Z 6W9A
• 分子名称: Ubiquitin-conjugating enzyme E2 D2, E3 ubiquitin-protein ligase RLIM, Ubiquitin, ... (5 entities in total)
• 機能のキーワード: ring e3 ligase, ubiquitin, ubiquitin conjugating enzyme, x-chromosome inactivation, ring, ligase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 113891.34

構造登録者

Middleton, A.J.,Day, C.L. (登録日: 2020-03-22, 公開日: 2020-05-20, 最終更新日: 2023-10-18)

主引用文献

Middleton, A.J.,Zhu, J.,Day, C.L.
The RING Domain of RING Finger 12 Efficiently Builds Degradative Ubiquitin Chains.
J.Mol.Biol., 432:3790-3801, 2020

PubMed Abstract: RNF12 is a widely expressed ubiquitin E3 ligase that is required for X-chromosome inactivation, regulation of LIM-domain containing transcription factors, and TGF-β signaling. A RING domain at the C terminus of RNF12 is important for its E3 ligase activity, and mutations in the RING domain are associated with X-linked intellectual disability. Here we have characterized ubiquitin transfer by RNF12, and show that the RING domain can bind to, and is active with, ubiquitin conjugating enzymes (E2s) that produce degradative ubiquitin chains. We report the crystal structures of RNF12 in complex with two of these E2 enzymes, as well as with an E2~Ub conjugate in a closed conformation. These structures form a basis for understanding the deleterious effect of a number of disease causing mutations. Comparison of the RNF12 structure with other monomeric RINGs suggests that a loop prior to the core RING domain has a conserved and essential role in stabilization of the active conformation of the bound E2~Ub conjugate. Together these findings provide a framework for better understanding substrate ubiquitylation by RNF12 and the impact of disease causing mutations.

PubMed: 32416094
DOI: 10.1016/j.jmb.2020.05.001

実験手法

X-RAY DIFFRACTION (3.19 Å)