Dataset Information

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

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Katja Bernfur

LAB HEAD: Herwig Schüler

PROVIDER: PXD067296 | Pride | 2025-09-29

REPOSITORIES: Pride

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			Action	DRS
	Katja_Blank_230328_595.d.zip	Other
	Katja_Blank_230328_639.d.zip	Other
	Katja_Carmen_230329_xlink_596.d.zip	Other
	Katja_Carmen_230329_xlink_598.d.zip	Other
	Katja_Carmen_230329_xlink_600.d.zip	Other

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

Ebenwaldner Carmen C García Saura Antonio Ginés AG Ekström Simon S Bernfur Katja K Moche Martin M Logan Derek T DT Cohen Michael S MS Schüler Herwig H

Nature communications 20251029 1

PARP15 is a mono-ADP-ribosyltransferase that targets an unknown set of proteins as well as RNA. Its evolutionary relationship with PARP14 suggests roles in antiviral defence; its localization to stress granules points to functions in the regulation of translation. Here we show that the transferase domain of PARP15 dimerizes in solution; the formation of dimers is a prerequisite for catalytic activity and monomeric mutant variants of the domain are inactive. In cells, dimer-disrupting mutations a ...[more]

PMID: 41162413

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