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Instruments / Technical Area	Publication Details	Published	Actions
B21-High Throughput SAXS I04-1-Macromolecular Crystallography (fixed wavelength) I04-Macromolecular Crystallography	Structural insights into ADP-ribosylation of ubiquitin by Deltex family E3 ubiquitin ligases Chatrin Chatrin , Mads Gabrielsen , Lori Buetow , Mark A. Nakasone , Syed F. Ahmed , David Sumpton , Gary J. Sibbet , Brian O. Smith , Danny Huang Science Advances 6 DOI: 10.1126/sciadv.abc0418 Diamond Proposal Number(s): [16258] Open Access Show Abstract ▼ 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 Gly76. 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.	Sep 2020

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Publication Details

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B21-High Throughput SAXS
I04-1-Macromolecular Crystallography (fixed wavelength)
I04-Macromolecular Crystallography

Structural insights into ADP-ribosylation of ubiquitin by Deltex family E3 ubiquitin ligases

Chatrin Chatrin , Mads Gabrielsen , Lori Buetow , Mark A. Nakasone , Syed F. Ahmed , David Sumpton , Gary J. Sibbet , Brian O. Smith , Danny Huang

Science Advances 6

DOI: 10.1126/sciadv.abc0418

Diamond Proposal Number(s): [16258]