Cryo-EM structure of constitutively active human Frizzled 7 in complex with heterotrimeric Gs
Bibliographic record
Abstract
The ten mammalian Frizzleds (FZD 1–10 ) belong to the class F of G protein-coupled receptors (GPCRs) and mediate WNT signaling through interaction with transducer proteins including Dishevelled (DVL) or heterotrimeric G proteins. 1 Their involvement in human disease has put FZDs at the forefront of drug targets, especially anti-cancer therapy. 2 However, no drugs have been developed for efficient pharmacological modulation of FZDs, partially owing to the limited understanding of FZD structure and activation mechanisms. 1 , 3 Among class F, FZD 7 is intensively pursued due to its relevance in various tumor models, particularly in intestinal cancers. 4 Detailed structures of the receptor complexes would allow for structure-guided discovery of new drug candidates. FZD 1–10 share structural similarity with the related class F member Smoothened (SMO), which mediates Hedgehog signaling and is a validated target for cancer therapy. 2 In an effort to understand the structural basis of FZD activation and transducer interaction, we solved the structure of human FZD 7 in complex with heterotrimeric mini G s (mG s ). 5
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".