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Open data
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Basic information
| Entry | Database: PDB / ID: 8j9n | |||||||||||||||||||||||||||||||||||||||||||||
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| Title | Gq bound FZD1 in ligand-free state | |||||||||||||||||||||||||||||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / FZD1-Gq / class-F / Frizzled receptor / Complex | |||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationmuscular septum morphogenesis / regulation of mesenchymal stem cell differentiation / autocrine signaling / astrocyte-dopaminergic neuron signaling / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / presynapse assembly / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / Wnt receptor activity / non-canonical Wnt signaling pathway ...muscular septum morphogenesis / regulation of mesenchymal stem cell differentiation / autocrine signaling / astrocyte-dopaminergic neuron signaling / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / presynapse assembly / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / Wnt receptor activity / non-canonical Wnt signaling pathway / membranous septum morphogenesis / endothelial cell differentiation / phospholipase C-activating serotonin receptor signaling pathway / PLC beta mediated events / Wnt-protein binding / regulation of platelet activation / entrainment of circadian clock / midbrain dopaminergic neuron differentiation / hard palate development / frizzled binding / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / PCP/CE pathway / Class B/2 (Secretin family receptors) / Wnt signalosome / regulation of canonical Wnt signaling pathway / Disassembly of the destruction complex and recruitment of AXIN to the membrane / glutamate receptor signaling pathway / outflow tract morphogenesis / phototransduction, visible light / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / negative regulation of BMP signaling pathway / photoreceptor outer segment / canonical Wnt signaling pathway / D1 dopamine receptor binding / regulation of presynapse assembly / positive regulation of osteoblast differentiation / neuropeptide signaling pathway / intracellular transport / postsynaptic cytosol / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / enzyme regulator activity / response to prostaglandin E / cellular response to glucagon stimulus / regulation of insulin secretion / GTPase activator activity / adenylate cyclase activator activity / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / trans-Golgi network membrane / TCF dependent signaling in response to WNT / Asymmetric localization of PCP proteins / PDZ domain binding / negative regulation of inflammatory response to antigenic stimulus / negative regulation of canonical Wnt signaling pathway / positive regulation of neuron projection development / G protein-coupled receptor binding / bone development / G protein-coupled receptor activity / platelet aggregation / cognition / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / neuron differentiation / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / blood coagulation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / sensory perception of smell / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / cell-cell signaling / GPER1 signaling Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human)![]() | |||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||||||||||||||||||||||||||||||||||||||
Authors | Lin, X. / Xu, F. | |||||||||||||||||||||||||||||||||||||||||||||
| Funding support | 1items
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Citation | Journal: Cell Discov / Year: 2024Title: A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways. Authors: Zhibin Zhang / Xi Lin / Ling Wei / Yiran Wu / Lu Xu / Lijie Wu / Xiaohu Wei / Suwen Zhao / Xiangjia Zhu / Fei Xu / ![]() Abstract: The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. ...The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts. | |||||||||||||||||||||||||||||||||||||||||||||
| History |
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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 | 8j9n.cif.gz | 209.7 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb8j9n.ent.gz | 158.7 KB | Display | PDB format |
| PDBx/mmJSON format | 8j9n.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 8j9n_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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| Full document | 8j9n_full_validation.pdf.gz | 1.1 MB | Display | |
| Data in XML | 8j9n_validation.xml.gz | 43.2 KB | Display | |
| Data in CIF | 8j9n_validation.cif.gz | 65.9 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j9/8j9n ftp://data.pdbj.org/pub/pdb/validation_reports/j9/8j9n | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 36111MC ![]() 8j9oC ![]() 8jh7C ![]() 8jhbC ![]() 8jhcC ![]() 8jhiC M: map data used to model this data C: citing same article ( |
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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
| #1: Protein | Mass: 64015.668 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FZD1 / Cell line (production host): SF9 / Production host: ![]() |
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| #2: Protein | Mass: 28820.500 Da / Num. of mol.: 1 / Mutation: G49D,E50N,A249D,S252D,I372A,V375I Source method: isolated from a genetically manipulated source Details: Chimeric protein MiniGQ / Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP, GNAQ, GAQ / Production host: ![]() |
| #3: Protein | Mass: 37416.930 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Cell line (production host): Hi5 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873 |
| #4: Protein | Mass: 7845.078 Da / Num. of mol.: 1 / Mutation: C68S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Cell line (production host): Hi5 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P59768 |
| #5: Antibody | Mass: 16054.232 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
| 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: FZD1-Gq complex in the ligand-free state / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | ||||||||||||||||
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| Source (natural) |
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| Source (recombinant) |
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| 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: FEI TITAN KRIOS |
| Electron gun | Electron source: OTHER / Accelerating voltage: 300 kV / Illumination mode: OTHER |
| Electron lens | Mode: OTHER / Nominal defocus max: 2200 nm / Nominal defocus min: 700 nm |
| Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
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| CTF correction | Type: NONE | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 544329 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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Homo sapiens (human)

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