Evidence map›Paper›PMID 32762848›Full record

ArticleeLife2020

Structure of human Frizzled5 by fiducial-assisted cryo-EM supports a heterodimeric mechanism of canonical Wnt signaling.

Naotaka Tsutsumi, Somnath Mukherjee, Deepa Waghray, Claudia Y Janda, Kevin M Jude, Yi Miao, John S Burg, Nanda Gowtham Aduri, Anthony A Kossiakoff, Cornelius Gati and 1 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
5.6field-weighted citation impact, top 3% of its field
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

86 citing papers in PubMed, 137 citations in OpenAlex.

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  5. The structure of the dopamine DScience advances · 2026
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  8. A novel fusion tool to enable G protein-coupled receptor structure determination.Acta crystallographica. Section D, Structural biology · 2026
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  9. Review
  10. Structure basis for C-C chemokine receptor 4 modulation by orthosteric and allosteric antagonists.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  12. Optimized bacterial expression of a synthetic BRIL antibody.Acta crystallographica. Section F, Structural biology communications · 2026
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  14. Review
  15. Review
  16. Review
  17. Structural insights into nonpeptide antagonist inhibition of somatostatin receptor subtype 5.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  20. Article

26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Naotaka TsutsumiDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States.ORCID 0000-0002-3617-7145
Somnath MukherjeeDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States.ORCID 0000-0001-5447-4496
Deepa WaghrayDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States.
Claudia Y JandaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States.ORCID 0000-0002-3307-2559
Kevin M JudeDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States.ORCID 0000-0002-3675-5136
Yi MiaoDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States.ORCID 0000-0003-0738-6041
John S BurgDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States.
Nanda Gowtham AduriDepartment of Structural Biology, Stanford University School of Medicine, Stanford, United States.ORCID 0000-0003-4301-7446
Anthony A KossiakoffDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, United States.
Cornelius GatiDepartment of Structural Biology, Stanford University School of Medicine, Stanford, United States.ORCID 0000-0003-3693-7009
K Christopher GarciaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States.ORCID 0000-0001-9273-0278
Howard Hughes Medical Institute · USStanford University · USSLAC National Accelerator Laboratory · USUniversity of Chicago · USPrincess Máxima Center · NL

Funding

X-ray Cryst. CoreP50GM082545 · NIGMS · UNIVERSITY OF UTAH · PI SUNDQUIST, WESLEY I. · 2007 to 2018
$51.1M
Chaperone-Assisted Structure Determination of Membrane ProteinsR01GM117372 · NIGMS · UNIVERSITY OF CHICAGO · PI ANTHONY A KOSSIAKOFF · 2016 to 2026
$4.0M
Structure-based Bioengineering of Wnt Surrogates for Intestinal Stem Cell Biology and TherapyR01DK115728 · NIDDK · STANFORD UNIVERSITY · PI GARCIA, KENAN CHRISTOPHER, KUO, CALVIN J · 2018 to 2022
$3.9M
Viral GPCR recognition of chemokines and engineered ligandsR01AI125320 · NIAID · STANFORD UNIVERSITY · PI GARCIA, KENAN CHRISTOPHER · 2016 to 2020
$2.0M
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI125320NIDDK NIH HHS R01 DK115728NIGMS NIH HHS P50 GM082545NIGMS NIH HHS R01 GM117372NIH HHS 1R01DK115728
6 · The paper itself

Abstract

Frizzleds (Fzd) are the primary receptors for Wnt morphogens, which are essential regulators of stem cell biology, yet the structural basis of Wnt signaling through Fzd remains poorly understood. Here we report the structure of an unliganded human Fzd5 determined by single-particle cryo-EM at 3.7 Å resolution, with the aid of an antibody chaperone acting as a fiducial marker. We also analyzed the topology of low-resolution XWnt8/Fzd5 complex particles, which revealed extreme flexibility between the Wnt/Fzd-CRD and the Fzd-TM regions. Analysis of Wnt/β-catenin signaling in response to Wnt3a versus a 'surrogate agonist' that cross-links Fzd to LRP6, revealed identical structure-activity relationships. Thus, canonical Wnt/β-catenin signaling appears to be principally reliant on ligand-induced Fzd/LRP6 heterodimerization, versus the allosteric mechanisms seen in structurally analogous class A G protein-coupled receptors, and Smoothened. These findings deepen our mechanistic understanding of Wnt signal transduction, and have implications for harnessing Wnt agonism in regenerative medicine.

Indexed as

Wnt Signaling PathwayCryoelectron MicroscopyFrizzled ReceptorsHumansFrizzled ReceptorsFZD5 protein, humancanonical Wnt/β-catenin signalingCryo-EMFrizzledhumanmolecular biophysicsstructural biologysurrogate Wnt agonistWnt

Identifiers

PMID32762848
PMCPMC7442489
OpenAlexW3048320307

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.