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Record W4407986918 · doi:10.1038/s41467-025-56796-9

Structures of TGF-β with betaglycan and signaling receptors reveal mechanisms of complex assembly and signaling

2025· article· en· W4407986918 on OpenAlexafffund
Łukasz Wieteska, Alexander B. Taylor, Emma K. Punch, Jonathan A. Coleman, Isabella O. Conway, Yeu‐Farn Lin, Chang‐Hyeock Byeon, Cynthia S. Hinck, Troy C. Krzysiak, Rieko Ishima, Fernando López‐Casillas, Peter Cherepanov, Daniel J. Bernard, Caroline S. Hill, Andrew P. Hinck

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicTGF-β signaling in diseases
Canadian institutionsMcGill University
FundersNational Center for Research ResourcesNational Institute of General Medical SciencesCanadian Institutes of Health ResearchNational Cancer InstituteU.S. Department of Health and Human ServicesGovernment of CanadaNational Institutes of HealthFrancis Crick InstituteWellcome Trust
KeywordsReceptorSignal transductionCell biologyEndoglinR-SMADTransforming growth factorBiologyTransforming growth factor betaLigand (biochemistry)Gene isoformChemistryBiochemistryGene

Abstract

fetched live from OpenAlex

Betaglycan (BG) is a transmembrane co-receptor of the transforming growth factor-β (TGF-β) family of signaling ligands. It is essential for embryonic development, tissue homeostasis and fertility in adults. It functions by enabling binding of the three TGF-β isoforms to their signaling receptors and is additionally required for inhibin A (InhA) activity. Despite its requirement for the functions of TGF-βs and InhA in vivo, structural information explaining BG ligand selectivity and its mechanism of action is lacking. Here, we determine the structure of TGF-β bound both to BG and the signaling receptors, TGFBR1 and TGFBR2. We identify key regions responsible for ligand engagement, which has revealed binding interfaces that differ from those described for the closely related co-receptor of the TGF-β family, endoglin, thus demonstrating remarkable evolutionary adaptation to enable ligand selectivity. Finally, we provide a structural explanation for the hand-off mechanism underlying TGF-β signal potentiation.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.013
GPT teacher head0.290
Teacher spread0.277 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations24
Published2025
Admission routes2
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicTGF-β signaling in diseasesFrench-language works237,207