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

ABSTRACT: 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 abrogate catalytic activity and alter the subcellular localization of the full-length protein. Using biophysical methods, including X-ray crystallography and HDX-MS, we provide evidence for a regulatory mechanism by which dimerization enables correct target engagement rather than NAD⁺ co-s

SUBMITTER: Ebenwaldner C 

PROVIDER: S-EPMC12572374 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature