6Y3J

RING-DTC domains of Deltex 2, bound to ADP-ribose

6Y3J の概要

• エントリーDOI: 10.2210/pdb6y3j/pdb
• 関連するPDBエントリー: 6Y22 6Y2X
• 分子名称: Probable E3 ubiquitin-protein ligase DTX2, ADENOSINE-5-DIPHOSPHORIBOSE, ZINC ION, ... (4 entities in total)
• 機能のキーワード: ubiquitination, e3 ring ligase, ubiquitin, par-binding, ligase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26624.51

構造登録者

Gabrielssen, M.,Buetow, L.,Huang, D.T. (登録日: 2020-02-18, 公開日: 2020-09-02, 最終更新日: 2024-01-24)

主引用文献

Ahmed, S.F.,Buetow, L.,Gabrielsen, M.,Lilla, S.,Chatrin, C.,Sibbet, G.J.,Zanivan, S.,Huang, D.T.
DELTEX2 C-terminal domain recognizes and recruits ADP-ribosylated proteins for ubiquitination.
Sci Adv, 6:-, 2020

PubMed Abstract: Cross-talk between ubiquitination and ADP-ribosylation regulates spatiotemporal recruitment of key players in many signaling pathways. The DELTEX family ubiquitin ligases (DTX1 to DTX4 and DTX3L) are characterized by a RING domain followed by a C-terminal domain (DTC) of hitherto unknown function. Here, we use two label-free mass spectrometry techniques to investigate the interactome and ubiquitinated substrates of human DTX2 and identify a large proportion of proteins associated with the DNA damage repair pathway. We show that DTX2-catalyzed ubiquitination of these interacting proteins requires PARP1/2-mediated ADP-ribosylation and depends on the DTC domain. Using a combination of structural, biochemical, and cell-based techniques, we show that the DTX2 DTC domain harbors an ADP-ribose-binding pocket and recruits poly-ADP-ribose (PAR)-modified proteins for ubiquitination. This PAR-binding property of DTC domain is conserved across the DELTEX family E3s. These findings uncover a new ADP-ribose-binding domain that facilitates PAR-dependent ubiquitination.

PubMed: 32937373
DOI: 10.1126/sciadv.abc0629

実験手法

X-RAY DIFFRACTION (2.6 Å)