9IFV
PARP15 catalytic domain mutant (R576E) in complex with 3-aminobenzamide
Summary for 9IFV
| Entry DOI | 10.2210/pdb9ifv/pdb |
| Descriptor | Protein mono-ADP-ribosyltransferase PARP15, 3-aminobenzamide (3 entities in total) |
| Functional Keywords | adp-ribosyltransferase, parp, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 51095.06 |
| Authors | Ebenwaldner, C.,Logan, D.T.,Schuler, H.,Moche, M. (deposition date: 2025-02-18, release date: 2025-10-08, Last modification date: 2025-11-12) |
| Primary citation | Ebenwaldner, C.,Garcia Saura, A.G.,Ekstrom, S.,Bernfur, K.,Moche, M.,Logan, D.T.,Cohen, M.S.,Schuler, H. Regulation of ADP-ribosyltransferase activity by ART domain dimerization in PARP15. Nat Commun, 16:9567-9567, 2025 Cited by PubMed 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-substrate binding, and by which the two protomers of the dimer operate independently of one another. Together, our results uncover a regulatory mechanism in a PARP family enzyme. PubMed: 41162413DOI: 10.1038/s41467-025-65315-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.431 Å) |
Structure validation
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