Inhibitory Module of Ets-1 Allosterically Regulates DNA Binding through a Dipole-facilitated Phosphate Contact
Bibliographic record
Abstract
DNA binding of the transcription factor Ets-1 is negatively regulated by three inhibitory helices that lie near the ETS domain. The current model suggests that this negative regulation, termed autoinhibition, is caused by the energetic expense of a DNA-induced structural transition that includes the unfolding of one inhibitory helix. This report investigates the role of helix H1 of the ETS domain in the autoinhibition mechanism. Previous structural studies modeled the inhibitory helices packing together and connecting with helix H1, suggesting a role of this helix in the configuration of an inhibitory module. Recently, high-resolution structures of the ETS domain-DNA interface indicate that the N terminus of helix H1 directly contacts DNA. The contact, which is augmented by the macrodipole of helix H1, consists of a hydrogen bond between the amide NH of leucine 337 in helix H1 and the oxygen of a corresponding phosphate. We propose that this hydrogen bond positions helix H1 to be a link between autoinhibition and DNA binding. Four independent approaches tested this hypothesis. First, the hydrogen bond was disrupted by removal of the phosphate in a missing phosphate analysis. Second, base pairs that surround the helix H1-contacting phosphate and appear to dictate DNA backbone conformation were mutated. Next, a hydrophobic residue in helix H1 that is expected to position the N terminus of the helix was altered. Finally, a residue on the surface of helix H1 that may contact the inhibitory elements was changed. In each case DNA binding and autoinhibition was affected. Taken together, the results demonstrate the role of the dipole-facilitated phosphate contact in DNA binding. Furthermore, the findings support a model in which helix H1 links the inhibitory elements to the ETS domain. We speculate that this helix, which is conserved in all Ets proteins, provides a common route to regulation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".