ArticleNature communications2024
Structural basis of Frizzled 4 in recognition of Dishevelled 2 unveils mechanism of WNT signaling activation.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Direct β-arrestin engagement by the non-canonical WNT receptor FZD6 via a shallow binding pocket.Acta pharmacologica Sinica · 2026Article
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Targeting YAP: mechanistic breakthroughs and therapeutic prospects in reversing organ fibrosis.Molecular and cellular biochemistry · 2026Review
- Decoding the Oncogenic Role of GNG10 in Colorectal Cancer: A Non-Canonical Wnt Pathway-Driven Mechanism.Journal of cellular and molecular medicine · 2026Article
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- Targeting frizzleds with small-molecule compounds-back to square one or light at the end of the tunnel?The Journal of biological chemistry · 2026Review
- Dishevelled PDZ domain targeting peptides modulate non-canonical Wnt5a/Ror signaling.Biochemistry and biophysics reports · 2026Article
- Targeting tumor-associated G-protein coupled receptors: beyond single-axis inhibition toward multidimensional regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- A Wnt-induced conformational phospho-switch in DVL3 controls association with Frizzled receptors and Wnt/β-catenin signaling.Science advances · 2026Article
- FlyPredictome: A structural atlas of predicted protein-protein interactions inbioRxiv : the preprint server for biology · 2026Article
- Frizzled-4 promotes bone formation in chickens via activation of the canonical Wnt signaling pathway.Poultry science · 2026Article
- Genetic recovery in an alpine climate-sensitive pika species during upward treeline shift.BMC genomics · 2026Article
- Development of the blood-brain barrier.Development (Cambridge, England) · 2026Review
- Secreted frizzled-related protein 2 as a context-dependent extracellular signaling hub in development, tissue remodeling, and disease.Frontiers in cell and developmental biology · 2026Review
- In silico docking yields small molecule negative allosteric modulators targeting the core of Frizzled 7.Nature communications · 2025Article
- Structural basis for regulation of Frizzled-4 signaling by the co-receptor Tetraspanin-12.bioRxiv : the preprint server for biology · 2025Article
- Article
- Wnt signalosome assembly is governed by conformational flexibility of Axin and by the AP2 clathrin adaptor.Nature communications · 2025Article
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- Frizzled receptors: gatekeepers of Wnt signaling in development and disease.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
21 authors.
Funding
Abstract
WNT signaling is fundamental in development and homeostasis, but how the Frizzled receptors (FZDs) propagate signaling remains enigmatic. Here, we present the cryo-EM structure of FZD4 engaged with the DEP domain of Dishevelled 2 (DVL2), a key WNT transducer. We uncover a distinct binding mode where the DEP finger-loop inserts into the FZD4 cavity to form a hydrophobic interface. FZD4 intracellular loop 2 (ICL2) additionally anchors the complex through polar contacts. Mutagenesis validates the structural observations. The DEP interface is highly conserved in FZDs, indicating a universal mechanism by which FZDs engage with DVLs. We further reveal that DEP mimics G-protein/β-arrestin/GRK to recognize an active conformation of receptor, expanding current GPCR engagement models. Finally, we identify a distinct FZD4 dimerization interface. Our findings delineate the molecular determinants governing FZD/DVL assembly and propagation of WNT signaling, providing long-sought answers underlying WNT signal transduction.
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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.