+Open data
-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 information : / muscular septum morphogenesis / regulation of mesenchymal stem cell differentiation / autocrine signaling / planar cell polarity pathway involved in neural tube closure / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / astrocyte-dopaminergic neuron signaling / canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation / hard palate development / Acetylcholine regulates insulin secretion ...: / muscular septum morphogenesis / regulation of mesenchymal stem cell differentiation / autocrine signaling / planar cell polarity pathway involved in neural tube closure / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / astrocyte-dopaminergic neuron signaling / canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation / hard palate development / Acetylcholine regulates insulin secretion / Wnt receptor activity / membranous septum morphogenesis / non-canonical Wnt signaling pathway / presynapse assembly / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / regulation of platelet activation / endothelial cell differentiation / Wnt-protein binding / midbrain dopaminergic neuron differentiation / entrainment of circadian clock / phototransduction, visible light / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / frizzled binding / glutamate receptor signaling pathway / PCP/CE pathway / regulation of canonical Wnt signaling pathway / Wnt signalosome / Class B/2 (Secretin family receptors) / Disassembly of the destruction complex and recruitment of AXIN to the membrane / action potential / outflow tract morphogenesis / PKA activation in glucagon signalling / : / hair follicle placode formation / regulation of presynapse assembly / negative regulation of BMP signaling pathway / photoreceptor outer segment / developmental growth / intracellular transport / D1 dopamine receptor binding / canonical Wnt signaling pathway / positive regulation of cAMP-mediated signaling / Hedgehog 'off' state / positive regulation of osteoblast differentiation / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / GTPase activator activity / trans-Golgi network membrane / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / G protein-coupled receptor activity / G protein-coupled receptor binding / PDZ domain binding / negative regulation of protein kinase activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / bone development / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / neuron differentiation / negative regulation of canonical Wnt signaling pathway / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / cognition / photoreceptor disc membrane / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / positive regulation of GTPase activity / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of DNA-binding transcription factor activity / positive regulation of neuron projection development / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Vicugna pacos (alpaca) | ||||||
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: 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 | 8j9n.cif.gz | 208.8 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 (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: 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: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9UP38 |
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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: Escherichia coli (E. coli) / References: UniProt: P63092, UniProt: P50148 |
#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.) Vicugna pacos (alpaca) / Production host: Escherichia coli (E. coli) |
-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: 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 |
-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) |
-Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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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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