6y3j
From Proteopedia
RING-DTC domains of Deltex 2, bound to ADP-ribose
Structural highlights
Function[DTX2_HUMAN] Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Probably acts both as a positive and negative regulator of Notch, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Functions as a ubiquitin ligase protein in vitro, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity. Publication Abstract from PubMedCross-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. DELTEX2 C-terminal domain recognizes and recruits ADP-ribosylated proteins for ubiquitination.,Ahmed SF, Buetow L, Gabrielsen M, Lilla S, Chatrin C, Sibbet GJ, Zanivan S, Huang DT Sci Adv. 2020 Aug 21;6(34). pii: 6/34/eabc0629. doi: 10.1126/sciadv.abc0629., Print 2020 Aug. PMID:32937373[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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