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Open data
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Basic information
| Entry | Database: PDB / ID: 8jhi | |||||||||||||||||||||||||||||||||||||||||||||
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| Title | FZD3-Gs complex | |||||||||||||||||||||||||||||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / FZD3 / Complex | |||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationdopaminergic neuron axon guidance / serotonergic neuron axon guidance / cell proliferation in midbrain / negative regulation of mitotic cell cycle, embryonic / establishment of planar polarity / midbrain morphogenesis / motor neuron migration / Wnt receptor activity / sympathetic ganglion development / non-canonical Wnt signaling pathway ...dopaminergic neuron axon guidance / serotonergic neuron axon guidance / cell proliferation in midbrain / negative regulation of mitotic cell cycle, embryonic / establishment of planar polarity / midbrain morphogenesis / motor neuron migration / Wnt receptor activity / sympathetic ganglion development / non-canonical Wnt signaling pathway / filopodium tip / Wnt-protein binding / post-anal tail morphogenesis / sensory perception of chemical stimulus / mu-type opioid receptor binding / commissural neuron axon guidance / corticotropin-releasing hormone receptor 1 binding / negative regulation of execution phase of apoptosis / PCP/CE pathway / Class B/2 (Secretin family receptors) / Wnt signaling pathway, planar cell polarity pathway / beta-2 adrenergic receptor binding / inner ear morphogenesis / positive regulation of neuroblast proliferation / PKA activation in glucagon signalling / hair follicle development / lateral plasma membrane / response to electrical stimulus / developmental growth / canonical Wnt signaling pathway / D1 dopamine receptor binding / Hedgehog 'off' state / insulin-like growth factor receptor binding / presynaptic active zone membrane / ionotropic glutamate receptor binding / adenylate cyclase activator activity / PDZ domain binding / neural tube closure / Asymmetric localization of PCP proteins / bone development / platelet aggregation / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / neuron differentiation / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / 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 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G beta:gamma signalling through BTK / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / positive regulation of cold-induced thermogenesis / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G alpha (12/13) signalling events / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / sensory perception of taste / Thrombin signalling through proteinase activated receptors (PARs) / adenylate cyclase-activating G protein-coupled receptor signaling pathway / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / fibroblast proliferation / G protein activity / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / apical plasma membrane / response to xenobiotic stimulus Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||||||||||||||||||||||||||||||||||||||
Authors | Xu, F. / Zhang, Z. | |||||||||||||||||||||||||||||||||||||||||||||
| 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 | 8jhi.cif.gz | 207.1 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb8jhi.ent.gz | 158.8 KB | Display | PDB format |
| PDBx/mmJSON format | 8jhi.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jh/8jhi ftp://data.pdbj.org/pub/pdb/validation_reports/jh/8jhi | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 36266MC ![]() 8j9nC ![]() 8j9oC ![]() 8jh7C ![]() 8jhbC ![]() 8jhcC 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: 28861.875 Da / Num. of mol.: 1 / Mutation: G44D,E45N,A249D,S252D,I372A,V375I Source method: isolated from a genetically manipulated source Details: minGas / Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1 / Production host: ![]() |
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| #2: Protein | Mass: 37069.543 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 |
| #3: Protein | Mass: 6261.229 Da / Num. of mol.: 1 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 |
| #4: Protein | Mass: 13711.284 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: ![]() |
| #5: Protein | Mass: 60076.348 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FZD3 / Cell line (production host): Sf9 / Production host: ![]() |
| 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: Complex of FZD3-Gs heterotrimer with Nb35. / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | ||||||||||||||||
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| Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||
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| Buffer solution | pH: 7.4 | ||||||||||||||||
| 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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
| Electron lens | Mode: DIFFRACTION / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
| Image recording | Electron dose: 20 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: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 141786 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi




Homo sapiens (human)
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Trichoplusia ni (cabbage looper)
FIELD EMISSION GUN