+Open data
-Basic information
Entry | Database: PDB / ID: 8jhb | ||||||
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Title | FZD6 Gs complex | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / FZD6 / Complex. | ||||||
Function / homology | Function and homology information embryonic nail plate morphogenesis / establishment of body hair planar orientation / cell proliferation in midbrain / Signaling by RNF43 mutants / Wnt receptor activity / midbrain morphogenesis / non-canonical Wnt signaling pathway / sensory perception of chemical stimulus / Wnt-protein binding / mu-type opioid receptor binding ...embryonic nail plate morphogenesis / establishment of body hair planar orientation / cell proliferation in midbrain / Signaling by RNF43 mutants / Wnt receptor activity / midbrain morphogenesis / non-canonical Wnt signaling pathway / sensory perception of chemical stimulus / Wnt-protein binding / mu-type opioid receptor binding / apicolateral plasma membrane / corticotropin-releasing hormone receptor 1 binding / PCP/CE pathway / Class B/2 (Secretin family receptors) / Wnt signaling pathway, planar cell polarity pathway / beta-2 adrenergic receptor binding / inner ear morphogenesis / PKA activation in glucagon signalling / hair follicle development / developmental growth / D1 dopamine receptor binding / canonical Wnt signaling pathway / Hedgehog 'off' state / Regulation of FZD by ubiquitination / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / adenylate cyclase activator activity / neural tube closure / G protein-coupled receptor activity / Olfactory Signaling Pathway / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / bone development / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / cytoplasmic vesicle membrane / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / negative regulation of canonical Wnt signaling pathway / Prostacyclin signalling through prostacyclin receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / negative regulation of DNA-binding transcription factor activity / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / platelet aggregation / platelet activation / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cold-induced thermogenesis / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / apical plasma membrane / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / ubiquitin protein ligase binding / protein-containing complex binding / endoplasmic reticulum membrane / GTP binding / cell surface / signal transduction / extracellular exosome / membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Xu, F. / Zhang, Z. | ||||||
Funding support | 1items
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Citation | Journal: Cell Discov / Year: 2024 Title: 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8jhb.cif.gz | 231.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8jhb.ent.gz | 179.2 KB | Display | PDB format |
PDBx/mmJSON format | 8jhb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jh/8jhb ftp://data.pdbj.org/pub/pdb/validation_reports/jh/8jhb | HTTPS FTP |
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-Related structure data
Related structure data | 36261MC 8j9nC 8j9oC 8jh7C 8jhcC 8jhiC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 31117.201 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: Escherichia coli (E. coli) / References: UniProt: Q5JWF2 |
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#2: 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 |
#3: Protein | Mass: 8417.766 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: 14845.516 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
#5: Protein | Mass: 61912.398 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FZD6 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O60353 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: FZD6-Gs complex with Nb35. / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | ||||||||||||||||
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Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||
Source (recombinant) |
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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 |
-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: 2000 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 20 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 530390 / Symmetry type: POINT | ||||||||||||||||||||||||
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