NMR characterization of novel interactions between p97 AAA+ ATPase and the p47 adaptor revealing insights into substrate delivery mechanism
Bibliographic record
Abstract
p97/VCP is an essential AAA+ ATPase involved in diverse cellular activities by interacting with an array of protein adaptors that recruit p97 for specific tasks. p47 is one of the adaptors that targets p97 for membrane remodeling by forming a stable complex with p97 through multivalent interactions. Here, we report a pair of previously unidentified interactions between the N-terminal part of p47 (residues 1–94) and the N-terminal domain (NTD) of p97. Using nuclear magnetic resonance (NMR) spectroscopy, we identify two binding sites on p47, one located on the ubiquitin-associated (UBA) domain and the other on the intrinsically disordered linker, that interact with the same basic patch on p97 NTD, driven by electrostatic forces. Reciprocal NMR titration experiments between p47 (residues 1–94) and p97 NTD reveal that these interactions are relatively weak in nature with dissociation constants on the order of hundreds of micromolar to millimolar in trans. Structural models of the two interactions are developed based on NMR chemical shift perturbations, which reveal details of the tentative binding interfaces. Our findings provide new insights into the mechanism by which ubiquitinated substrates are delivered from p47 to p97 for unfolding.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".