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Yorodumi- PDB-9z67: Cryo-EM structure of human Wntless-Wnt5a 2:2 complex - Composite map -
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Open data
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Basic information
| Entry | Database: PDB / ID: 9z67 | |||||||||||||||
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| Title | Cryo-EM structure of human Wntless-Wnt5a 2:2 complex - Composite map | |||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Wnt transporter / Wnt secretion / Wnt5a / Wnt signaling | |||||||||||||||
| Function / homology | Function and homology informationoptic cup formation involved in camera-type eye development / receptor tyrosine kinase-like orphan receptor binding / chemoattraction of serotonergic neuron axon / positive regulation of timing of anagen / negative regulation of cell proliferation in midbrain / primary heart field specification / chemorepulsion of dopaminergic neuron axon / postsynapse assembly / olfactory bulb interneuron development / positive regulation of protein kinase C activity ...optic cup formation involved in camera-type eye development / receptor tyrosine kinase-like orphan receptor binding / chemoattraction of serotonergic neuron axon / positive regulation of timing of anagen / negative regulation of cell proliferation in midbrain / primary heart field specification / chemorepulsion of dopaminergic neuron axon / postsynapse assembly / olfactory bulb interneuron development / positive regulation of protein kinase C activity / chemoattractant activity involved in axon guidance / melanocyte proliferation / negative regulation of mesenchymal cell proliferation / negative regulation of melanin biosynthetic process / Wnt signaling pathway, calcium modulating pathway / regulation of postsynaptic cytosolic calcium ion concentration / Wnt protein secretion / cementum mineralization / negative regulation of synapse assembly / macrophage derived foam cell differentiation / atrial septum development / positive regulation of Wnt protein secretion / secondary heart field specification / positive regulation of non-canonical Wnt signaling pathway / Negative regulation of TCF-dependent signaling by WNT ligand antagonists / WNT5A-dependent internalization of FZD2, FZD5 and ROR2 / WNT ligand biogenesis and trafficking / excitatory synapse assembly / anterior/posterior axis specification, embryo / embryonic skeletal system development / WNT5A-dependent internalization of FZD4 / positive regulation of macrophage cytokine production / face development / anterior/posterior axis specification / secondary palate development / exocrine pancreas development / positive regulation of neuron projection arborization / presynapse assembly / hindbrain development / positive regulation of T cell chemotaxis / genitalia development / ventricular septum development / non-canonical Wnt signaling pathway / Wnt-protein binding / WNT5:FZD7-mediated leishmania damping / lens development in camera-type eye / positive regulation of cytokine production involved in immune response / hematopoietic stem cell proliferation / positive regulation of response to cytokine stimulus / midbrain dopaminergic neuron differentiation / cartilage development / positive regulation of macrophage activation / mesoderm formation / positive regulation of ossification / positive regulation of type I interferon-mediated signaling pathway / PCP/CE pathway / Class B/2 (Secretin family receptors) / frizzled binding / regulation of postsynapse organization / inhibitory synapse assembly / Wnt signaling pathway, planar cell polarity pathway / regulation of canonical NF-kappaB signal transduction / negative regulation of fat cell differentiation / midbrain development / positive regulation of Rac protein signal transduction / positive regulation of protein localization to synapse / cell fate commitment / regulation of synapse organization / canonical Wnt signaling pathway / keratinocyte differentiation / epithelial to mesenchymal transition / cellular response to transforming growth factor beta stimulus / positive regulation of Wnt signaling pathway / postsynaptic modulation of chemical synaptic transmission / cellular response to retinoic acid / positive regulation of chemokine production / positive regulation of endothelial cell proliferation / endomembrane system / male gonad development / cellular response to calcium ion / positive regulation of apoptotic signaling pathway / positive regulation of endothelial cell migration / Wnt signaling pathway / axon guidance / positive regulation of fibroblast proliferation / cytokine activity / wound healing / positive regulation of interleukin-8 production / positive regulation of interleukin-1 beta production / positive regulation of neuron projection development / TCF dependent signaling in response to WNT / trans-Golgi network / clathrin-coated endocytic vesicle membrane / negative regulation of canonical Wnt signaling pathway / intracellular protein transport / Asymmetric localization of PCP proteins / cellular response to type II interferon / positive regulation of type II interferon production / phospholipid binding / positive regulation of interleukin-6 production Similarity search - Function | |||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.32 Å | |||||||||||||||
Authors | Ge, Y. / de Almeida Magalhaes, T. / Wu, H. / Yadav, G.P. / Wang, Z. / Salic, A. / Jiang, J. / Huang, P. | |||||||||||||||
| Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2026Title: Conformational cycling of the Wntless transporter drives trafficking and secretion of Wnt morphogens. Authors: Yunhui Ge / Taciani de Almeida Magalhaes / Hongjiang Wu / Dick J H van den Boomen / Thu Uyen Nguyen / Tongyi Dou / Gaya P Yadav / Sukyeong Lee / Zhao Wang / Andrew Lemoff / Xuemei Luo / ...Authors: Yunhui Ge / Taciani de Almeida Magalhaes / Hongjiang Wu / Dick J H van den Boomen / Thu Uyen Nguyen / Tongyi Dou / Gaya P Yadav / Sukyeong Lee / Zhao Wang / Andrew Lemoff / Xuemei Luo / Sumitha S Menon / Min Zhang / Jin Wang / Zhicheng Jin / Jiansen Jiang / Adrian Salic / Pengxiang Huang / ![]() Abstract: Wnt proteins are lipid-modified morphogens fundamental in development and disease. During Wnt biogenesis, the G-protein-coupled receptor (GPCR)-like transporter Wntless (WLS) escorts lipidated Wnts ...Wnt proteins are lipid-modified morphogens fundamental in development and disease. During Wnt biogenesis, the G-protein-coupled receptor (GPCR)-like transporter Wntless (WLS) escorts lipidated Wnts from the endoplasmic reticulum to the plasma membrane, then transfers them to extracellular carriers, forming active and soluble morphogen-carrier complexes. To dissect the mechanisms involved, we solve cryo-EM structures of Wnt-bound WLS and unliganded WLS, and perform structure-guided functional experiments. Wnts engage WLS via three conserved hairpins, which are all required for Wnt trafficking to the cell surface and carrier-mediated secretion. Wnt release from cells is driven by dramatic conformational changes in the WLS transmembrane domain, reminiscent of GPCR activation, together with WLS extracellular rearrangements. Unexpectedly, we find that Wnt5a bound to WLS forms dimers, with implications for Wnt signaling. These findings define the mechanism of WLS conformational cycling that governs the intracellular transport and extracellular release of Wnt morphogens, essential steps in the Wnt pathway. | |||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9z67.cif.gz | 375.3 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9z67.ent.gz | 273.9 KB | Display | PDB format |
| PDBx/mmJSON format | 9z67.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/z6/9z67 ftp://data.pdbj.org/pub/pdb/validation_reports/z6/9z67 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 73838MC ![]() 9z4hC ![]() 9z4oC C: citing same article ( M: map data used to model this data |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Protein , 2 types, 4 molecules ACBD
| #1: Protein | Mass: 38832.180 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WNT5A / Production host: Homo sapiens (human) / References: UniProt: P41221#2: Protein | Mass: 66088.141 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WLS, C1orf139, GPR177, UNQ85/PRO18667 / Production host: Homo sapiens (human) / References: UniProt: Q5T9L3 |
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-Sugars , 2 types, 6 molecules 
| #3: Polysaccharide | Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / |
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-Non-polymers , 3 types, 6 molecules 




| #4: Chemical | | #6: Chemical | #7: Chemical | |
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-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: human Wntless-Wnt5a 2:2 complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 800 nm |
| Image recording | Electron dose: 50.83 e/Å2 / Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
| 3D reconstruction | Resolution: 3.32 Å / Resolution method: OTHER / Num. of particles: 174062 / Symmetry type: POINT | ||||||||||||||||
| Refinement | Cross valid method: NONE |
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About Yorodumi



Homo sapiens (human)
United States, 1items
Citation







PDBj













FIELD EMISSION GUN