Unknown

Dataset Information

0

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 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.

SUBMITTER: Chatrin C 

PROVIDER: S-EPMC7500938 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5556935 | BioStudies
2020-01-01 | S-EPMC7442474 | BioStudies
2021-09-09 | PXD017807 | Pride
1000-01-01 | S-EPMC4070648 | BioStudies
2015-01-01 | S-EPMC4653074 | BioStudies
2021-05-28 | PXD018811 | Pride
2021-04-23 | PXD025195 | Pride
1000-01-01 | S-EPMC4055268 | BioStudies
1000-01-01 | S-EPMC5095532 | BioStudies
| S-EPMC6456868 | BioStudies