The DNA target determines the dimerization partner selected by bHLHZ-like hybrid proteins AhRJun and ArntFos
Bibliographic record
Abstract
Abstract The molecular basis of protein–partner selection and DNA binding of the basic helix–loop–helix (bHLH) and basic region-leucine zipper (bZIP) superfamilies of dimeric transcription factors is fundamental toward understanding gene regulation. Because these families share structural similarities, we swapped the bHLH and leucine zipper (LZ) modules between families to uncover how individual modules influence protein-partnering and protein:DNA complexation. We previously described ArntFos, a bHLHZ-like hybrid of the bHLH domain from the bHLH/PAS protein Arnt and LZ from the bZIP protein c-Fos, binding to the Arnt E-box site (TCACGTGA) as a homodimer. Herein, we describe a heterodimer between ArntFos and AhRJun, a hybrid of the bHLH domain from AhR and LZ of JunD. We designed AhRJun and ArntFos to heterodimerize, given the strong interaction between native AhR/Arnt and Jun/Fos, but the hybrids showed no preference for hetero- or homo-dimerization in Y2H assays. However, adding a specific DNA target drove the formation of a single dimeric protein species over others. EMSA showed that the AhRJun/ArntFos heterodimer binds to the cognate DNA site XRE1 (TTGCGTG) with Kd = 337 nM. Unexpectedly, the palindromic Arnt E-box drove the binding of the AhRJun/ArntFos heterodimer (Kd = 276 nM)—not the ArntFos homodimer—that binds to the Arnt E-box. However, the dimerization preference switched to the ArntFos homodimer when the variant Max E-box (CCACGTGG) was used. We conclude that the DNA sites themselves are the primary determinants of dimerization specificity for AhRJun and ArntFos, not the JunD and c-Fos LZs, a result that sheds light on the dynamics of protein/protein and protein:DNA interactions and the structural modularity of bHLH and bZIP proteins.
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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) | 0.002 | 0.001 |
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".