Evidence map›Paper›PMID 40011426›Full record

ArticleNature communications2025

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

Łukasz Wieteska, Alexander B Taylor, Emma Punch, Jonathan A Coleman, Isabella O Conway, Yeu-Farn Lin, Chang-Hyeock Byeon, Cynthia S Hinck, Troy Krzysiak, Rieko Ishima and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Molecular Engineering of the Helminth TGF-β Mimetics, TGM1 and TGM4, Reveals a Novel Antagonist of TGF-β Signaling in Fibroblasts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Beyond labeling: differential AcRegenerative biomaterials · 2026
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Łukasz WieteskaDepartment of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-5890-6513
Alexander B TaylorDepartment of Biochemistry & Structural Biology and Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0003-3517-6033
Emma PunchChromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Jonathan A ColemanDepartment of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-0001-6195
Isabella O ConwayDepartment of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Yeu-Farn LinDepartment of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-2880-4532
Chang-Hyeock ByeonDepartment of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-9997-7708
Cynthia S HinckDepartment of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Troy KrzysiakDepartment of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Rieko IshimaDepartment of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Fernando López-CasillasDepartmento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, UNAM, Mexico City, Mexico.ORCID http://orcid.org/0000-0002-3689-1824
Peter CherepanovChromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.ORCID http://orcid.org/0000-0002-0634-538X
Daniel J BernardDepartment of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0001-5365-5586
Caroline S HillDevelopmental Signalling Laboratory, The Francis Crick Institute, London, NW1 1AT, UK. caroline.hill@crick.ac.uk.ORCID http://orcid.org/0000-0002-8632-0480
Andrew P HinckDepartment of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA. ahinck@pitt.edu.ORCID http://orcid.org/0000-0003-3320-8054

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Robin Jean Leach · 1991 to 2026
$59.1M
User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI Nozomi Ando, J Christopher Fromme · 2018 to 2026
$34.2M
LIGAND/RECEPTOR INTERACTIONS IN THE TGF BETA SUPERFAMILYR01GM058670 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HINCK, ANDREW P · 1999 to 2017
$3.6M
HTS for TGF-beta receptor assembly inhibitors with anti-tumor and anti-fibrosis activitiesR01CA233622 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HINCK, ANDREW P, JOHNSTON, PAUL A. · 2019 to 2022
$2.0M
Cryo-electron microscopeS10OD025009 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CONWAY, JAMES F. · 2018 to 2018
$2.0M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Pixel Array Detector for X-ray CrystallographyS10RR029205 · NCRR · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2010 to 2010
$1.8M
Direct electron detecting (DED) cameraS10OD019995 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CONWAY, JAMES F. · 2015 to 2015
$548k
Upgrade of a Core Laboratory Macromolecular X-ray Diffraction SystemS10OD030374 · OD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI TAYLOR, ALEXANDER B · 2021 to 2021
$439k
Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) PJT-191766NCI NIH HHS P30 CA054174NCI NIH HHS R01 CA233622NCRR NIH HHS S10 RR029205NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM058670NIH HHS S10 OD019995NIH HHS S10 OD021527NIH HHS S10 OD025009NIH HHS S10 OD030374U.S. Department of Health & Human Services | National Institutes of Health (NIH) CA233622U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM58670Wellcome Trust CC2021Wellcome Trust CC2058
6 · The paper itself

Abstract

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.

Indexed as

ProteoglycansReceptors, Transforming Growth Factor betaTransforming Growth Factor betaAnimalsCrystallography, X-RayEndoglinHumansInhibinsLigandsModels, MolecularProtein BindingReceptor, Transforming Growth Factor-beta Type IReceptor, Transforming Growth Factor-beta Type IISignal TransductionbetaglycanEndoglinInhibinsLigandsProteoglycansReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type IReceptor, Transforming Growth Factor-beta Type IITGFBR1 protein, humanTGFBR2 protein, humanTransforming Growth Factor beta

Identifiers

PMID40011426
PMCPMC11865472

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.