6Y22

RING-DTC domains of Deltex 2, Form 1

Summary for 6Y22

• Entry DOI: 10.2210/pdb6y22/pdb
• Descriptor: Probable E3 ubiquitin-protein ligase DTX2, ZINC ION (3 entities in total)
• Functional Keywords: ubiquitination, e3 ring ligase, ubiquitin, par-binding, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 26065.19

Authors

Gabrielssen, M.,Buetow, L.,Huang, D.T. (deposition date: 2020-02-14, release date: 2020-09-02, Last modification date: 2024-05-15)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.069 Å)