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

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 ubiqu

SUBMITTER: Chatrin C 

PROVIDER: S-EPMC7500938 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature