PXD061403

PXD061403 is an original dataset announced via ProteomeXchange.

Title	Regulation of ADP-ribosyltransferase activity by ART domain dimerization in PARP15
Description	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.
HostingRepository	PRIDE
AnnounceDate	2025-10-02
AnnouncementXML	Submission_2025-10-02_02:01:51.034.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Simon Ekström
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-03 08:14:04	ID requested
⏵ 1	2025-10-02 02:01:51	announced

Dataset with its publication pending

submitter keyword: HDX-MS, PARP15

Herwig Schüler
contact affiliation	Division of Biochemistry and Structural Biology, Department of Chemistry, Lund University, SE-22362, Lund, Sweden
contact email	herwig.schuler@biochemistry.lu.se
lab head
Simon Ekström
contact affiliation	BioMS - Swedish National Infrastructure for Biological Mass Spectrometry, Lund University, BMC D1330, 221 84 Lund, Sweden
contact email	simon.ekstrom@med.lu.se
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD061403

PRIDE project URI

• PRIDE
  1. PXD061403
     1. Label: PRIDE project
     2. Name: Regulation of ADP-ribosyltransferase activity by ART domain dimerization in PARP15