Evidence map›Paper›PMID 34315898›Full record

ArticleNature communications2021

Cryo-EM structure of human Wntless in complex with Wnt3a.

Qing Zhong, Yanyu Zhao, Fangfei Ye, Zaiyu Xiao, Gaoxingyu Huang, Meng Xu, Yuanyuan Zhang, Xiechao Zhan, Ke Sun, Zhizhi Wang and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

27 citing papers in PubMed, 57 citations in OpenAlex.

  1. MultilevelCurrent research in structural biology · 2026
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  6. Structural basis for Porcupine inhibition.Communications chemistry · 2025
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  11. Bioinformatic Analysis of WNT Family Proteins.Bioinformatics and biology insights · 2025
    Article
  12. Frizzled receptors: gatekeepers of Wnt signaling in development and disease.Frontiers in cell and developmental biology · 2025
    Review
  13. Article
  14. Synthesis and Frizzled-receptor binding of a WNT5A hairpin-3 peptide.Chemical communications (Cambridge, England) · 2024
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis.In vitro cellular & developmental biology. Animal · 2024
    Review
  20. Article
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

18 authors at 3 institutions in 1 country.

Qing Zhong *Fudan University, Shanghai, China.
Yanyu Zhao *Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Fangfei Ye *Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Zaiyu Xiao *Fudan University, Shanghai, China.
Gaoxingyu HuangKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Meng XuKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Yuanyuan ZhangKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Xiechao ZhanKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Ke SunKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Zhizhi WangSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Shanshan ChengSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Shan FengKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Xiuxiu ZhaoKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Jizhong ZhangKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Peilong LuKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.ORCID 0000-0001-5894-9268
Wenqing XuSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Qiang ZhouKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China. zhouqiang@westlake.edu.cn.ORCID 0000-0002-6237-8813
Dan MaKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China. madan@westlake.edu.cn.ORCID 0000-0002-6208-2262
Westlake University · CNShanghaiTech University · CNFudan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Wntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas aberrant Wnt signaling is tightly associated with many human diseases including cancers. Here, we report the cryo-EM structure of human WLS in complex with Wnt3a, the most widely studied Wnt, at 2.2 Å resolution. The transmembrane domain of WLS bears a GPCR fold, with a conserved core cavity and a lateral opening. Wnt3a interacts with WLS at multiple interfaces, with the lipid moiety on Wnt3a traversing a hydrophobic tunnel of WLS transmembrane domain and inserting into membrane. A β-hairpin of Wnt3a containing the conserved palmitoleoylation site interacts with WLS extensively, which is crucial for WLS-mediated Wnt secretion. The flexibility of the Wnt3a loop/hairpin regions involved in the multiple binding sites indicates induced fit might happen when Wnts are bound to different binding partners. Our findings provide important insights into the molecular mechanism of Wnt palmitoleoylation, secretion and signaling.

Indexed as

Cryoelectron MicroscopyFrizzled ReceptorsHeLa CellsHumansIntracellular Signaling Peptides and ProteinsModels, MolecularProtein ConformationReceptors, G-Protein-CoupledWnt3A ProteinFrizzled ReceptorsIntracellular Signaling Peptides and ProteinsReceptors, G-Protein-CoupledWLS protein, humanWnt3A Protein

Identifiers

PMID34315898
PMCPMC8316347
OpenAlexW3131125337

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.