Regulation of ADP-ribosyltransferase activity by ART domain dimerization in PARP15
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".