Proteomics

Dataset Information

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Regulation of ADP-ribosyltransferase activity by ART domain dimerization in PARP15


ABSTRACT: PARP15 is a mono-ADP-ribosyltransferase with unknown functions. Its evolutionary relationship with PARP14 suggests roles in antiviral defense; its ability to modify RNA and localization to stress granules point to functions in the regulation of translation. PARP15 also modifies itself and other proteins using its ADP-ribosyltransferase (ART) domain and contains two macrodomains predicted to bind ADP-ribosyl on targets. We used biochemical and biophysical analysis to study how the ADP-ribosyltransferase activity of PARP15 is regulated. Here we show that the catalytic domain of PARP15 dimerizes, forming the same dimer interface in solution that had already been captured by X-ray crystallography of the domain. Furthermore, we show that the formation of dimers is a prerequisite for catalytic activity and that monomeric mutant variants of the domain were catalytically inactive. Our findings suggest a regulatory mechanism by which dimerization is linked to either target engagement or placement of a catalytic residue, rather than NAD+ co-substrate binding, and by which the two protomers of the dimer operate independent of one another. Together, our results uncover a novel mechanism of regulation in a PARP family enzyme, which might inspire new avenues of pharmacological intervention.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Acute Leukemia

SUBMITTER: Simon Ekström  

LAB HEAD: Herwig Schüler

PROVIDER: PXD061403 | Pride | 2025-10-02

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
RAW_RUN1_PARP15.zip Other
RAW_Run2_PARP15.zip Other
peptide_pool_run1.csv Csv
peptide_pool_run2.csv Csv
table_S1.xlsx Xlsx
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