Crystal structure and mutagenesis of a nucleic acid–binding BRCT domain in human PARP4
Bibliographic record
Abstract
PARP4 is an ADP-ribosyltransferase typically associated with the cytoplasmic vault organelle. PARP4 has a distinct domain composition relative to other PARP enzymes; however, the N-terminal region of PARP4 is homologous to a collection of domains found in PARP1, a regulator of multiple nuclear processes including the cellular response to DNA damage. The N-terminal region of PARP4 interacts in vitro with nucleic acid, in particular a noncoding RNA associated with vault particles, and a BRCT domain is implicated in this interaction. Here, we report the X-ray structure of the BRCT domain of PARP4 and structure-based mutagenesis that interrogates the nucleic acid-binding activity using vault RNA. The isolated BRCT domain is capable of mediating interaction with vault RNA, and we identified four BRCT mutants that disrupt vault RNA interaction to varying degrees. X-ray structures of the BRCT mutants indicate that perturbations to an electropositive region of the BRCT surface underlie the loss of nucleic acid binding. Comparison to other nucleic acid-binding BRCT domains highlights distinct features of the PARP4 BRCT structure. The study presents the experimental structure of the PARP4 BRCT domain, establishes this domain as nucleic acid-binding module, and provides PARP4 BRCT mutants that can be used to investigate PARP4 cellular functions.
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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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".