Transmembrane association of DDR1 and DDR2 mediated by Leucine zipper motifs
Bibliographic record
Abstract
Discoidin domain receptors (DDRs) are single-pass transmembrane proteins belonging to receptor tyrosine kinases (RTKs) family, which are activated by collagen ligands with unusual slow, sustained kinetics, distinguishing them from canonical RTKs. While DDRs play critical roles in cell adhesion, differentiation, and cancer progression, their activation mechanisms remain partly understood. Here, we investigated the transmembrane domains (TMDs) of DDR1 and DDR2 to elucidate their interaction dynamics in membrane. Using bacterial adenylate cyclase two-hybrid (BACTH) assays, we demonstrated robust homotypic interactions and even stronger heterotypic associations between DDRTMDs. NMR spectroscopy of DDR1TMD and DDR2TMD reconstituted in lipid bilayer-mimetic bicelles showed obvious chemical shift alterations, further validating the stability of their heterocomplex formation. Systematic mutagenesis identified leucine zipper motifs rather than GXXXA motifs mediated both homo- and hetero-associations of DDR1TMD and DDR2TMD. These findings demonstrated the TMD as a critical mediator of DDRs oligomerization and revealed their interaction patterns within membrane. Our study advances the understanding of DDR signaling regulation and highlights transmembrane domain interactions as potential targets for modulating DDR-related pathologies.
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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".