6Y5N

RING-DTC domain of Deltex1

Summary for 6Y5N

• Entry DOI: 10.2210/pdb6y5n/pdb
• Descriptor: E3 ubiquitin-protein ligase DTX1, ZINC ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: ubiquitination, e3 ring ligase, nad binding, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 52596.17

Authors

Gabrielsen, M.,Buetow, L.,Huang, D.T. (deposition date: 2020-02-25, release date: 2020-09-30, Last modification date: 2024-05-15)

Primary citation

Chatrin, C.,Gabrielsen, M.,Buetow, L.,Nakasone, M.A.,Ahmed, S.F.,Sumpton, D.,Sibbet, G.J.,Smith, B.O.,Huang, D.T.
Structural insights into ADP-ribosylation of ubiquitin by Deltex family E3 ubiquitin ligases.
Sci Adv, 6:-, 2020

PubMed Abstract: Cellular cross-talk between ubiquitination and other posttranslational modifications contributes to the regulation of numerous processes. One example is ADP-ribosylation of the carboxyl terminus of ubiquitin by the E3 DTX3L/ADP-ribosyltransferase PARP9 heterodimer, but the mechanism remains elusive. Here, we show that independently of PARP9, the conserved carboxyl-terminal RING and DTC (Deltex carboxyl-terminal) domains of DTX3L and other human Deltex proteins (DTX1 to DTX4) catalyze ADP-ribosylation of ubiquitin's Gly Structural studies reveal a hitherto unknown function of the DTC domain in binding NAD Deltex RING domain recruits E2 thioesterified with ubiquitin and juxtaposes it with NAD bound to the DTC domain to facilitate ADP-ribosylation of ubiquitin. This ubiquitin modification prevents its activation but is reversed by the linkage nonspecific deubiquitinases. Our study provides mechanistic insights into ADP-ribosylation of ubiquitin by Deltex E3s and will enable future studies directed at understanding the increasingly complex network of ubiquitin cross-talk.

PubMed: 32948590
DOI: 10.1126/sciadv.abc0418

Experimental method

X-RAY DIFFRACTION (1.88 Å)