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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 | |||||||||||||||||||||||||||||||||||||||||||||
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Keywords | MEMBRANE PROTEIN / FZD1-Gq / class-F / Frizzled receptor / Complex | |||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationregulation of mesenchymal stem cell differentiation / astrocyte-dopaminergic neuron signaling / positive regulation of gonadotropin secretion / autocrine signaling / phospholipase C-activating tachykinin receptor signaling pathway / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / presynapse assembly / Acetylcholine regulates insulin secretion / Wnt receptor activity / sensory perception of itch ...regulation of mesenchymal stem cell differentiation / astrocyte-dopaminergic neuron signaling / positive regulation of gonadotropin secretion / autocrine signaling / phospholipase C-activating tachykinin receptor signaling pathway / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / presynapse assembly / Acetylcholine regulates insulin secretion / Wnt receptor activity / sensory perception of itch / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / non-canonical Wnt signaling pathway / Wnt-protein binding / phospholipase C-activating serotonin receptor signaling pathway / regulation of platelet activation / PLC beta mediated events / entrainment of circadian clock / positive regulation of membrane depolarization / phototransduction, visible light / midbrain dopaminergic neuron differentiation / frizzled binding / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / PCP/CE pathway / Class B/2 (Secretin family receptors) / Wnt signalosome / Disassembly of the destruction complex and recruitment of AXIN to the membrane / regulation of canonical Wnt signaling pathway / glutamate receptor signaling pathway / positive regulation of osteoblast differentiation / canonical Wnt signaling pathway / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / regulation of skeletal muscle contraction / developmental growth / hair follicle placode formation / PKA activation in glucagon signalling / renal water homeostasis / intracellular transport / photoreceptor outer segment / postsynaptic cytosol / D1 dopamine receptor binding / regulation of presynapse assembly / vascular endothelial cell response to laminar fluid shear stress / hormone-mediated signaling pathway / Hedgehog 'off' state / activation of adenylate cyclase activity / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to acidic pH / cellular response to glucagon stimulus / intracellular glucose homeostasis / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / adenylate cyclase activator activity / positive regulation of insulin secretion involved in cellular response to glucose stimulus / trans-Golgi network membrane / mast cell degranulation / GTPase activator activity / positive regulation of neuron projection development / positive regulation of insulin secretion / PDZ domain binding / TCF dependent signaling in response to WNT / negative regulation of inflammatory response to antigenic stimulus / neuropeptide signaling pathway / Asymmetric localization of PCP proteins / response to prostaglandin E / bone development / platelet aggregation / G protein-coupled receptor binding / cognition / blood coagulation / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / cytoplasmic side of plasma membrane / Olfactory Signaling Pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / Activation of the phototransduction cascade / glucose homeostasis / G protein-coupled acetylcholine receptor signaling pathway / sensory perception of smell / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / neuron differentiation / cell-cell signaling / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus 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. | |||||||||||||||||||||||||||||||||||||||||||||
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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
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/j9/8j9n ftp://data.pdbj.org/pub/pdb/validation_reports/j9/8j9n | HTTPS FTP |
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-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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| 1 |
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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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microscopy


