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Open data
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Basic information
Entry | Database: PDB / ID: 8jhb | ||||||
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Title | FZD6 Gs complex | ||||||
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![]() | MEMBRANE PROTEIN / FZD6 / Complex. | ||||||
Function / homology | ![]() embryonic nail plate morphogenesis / establishment of body hair planar orientation / cell proliferation in midbrain / Signaling by RNF43 mutants / midbrain morphogenesis / non-canonical Wnt signaling pathway / Wnt receptor activity / sensory perception of chemical stimulus / Wnt-protein binding / apicolateral plasma membrane ...embryonic nail plate morphogenesis / establishment of body hair planar orientation / cell proliferation in midbrain / Signaling by RNF43 mutants / midbrain morphogenesis / non-canonical Wnt signaling pathway / Wnt receptor activity / sensory perception of chemical stimulus / Wnt-protein binding / apicolateral plasma membrane / PCP/CE pathway / Class B/2 (Secretin family receptors) / Wnt signaling pathway, planar cell polarity pathway / inner ear morphogenesis / PKA activation in glucagon signalling / mu-type opioid receptor binding / hair follicle development / developmental growth / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / canonical Wnt signaling pathway / Hedgehog 'off' state / beta-2 adrenergic receptor binding / Regulation of FZD by ubiquitination / adenylate cyclase activator activity / neural tube closure / G protein-coupled receptor activity / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / bone development / cytoplasmic vesicle membrane / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / negative regulation of canonical Wnt signaling pathway / Thromboxane signalling through TP receptor / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / negative regulation of DNA-binding transcription factor activity / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / platelet activation / 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 / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / platelet aggregation / 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 / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / positive regulation of cold-induced thermogenesis / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / 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 | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
![]() | Xu, F. / Zhang, Z. | ||||||
Funding support | 1items
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![]() | ![]() 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: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 231.7 KB | Display | ![]() |
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PDB format | ![]() | 179.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 45.3 KB | Display | |
Data in CIF | ![]() | 66.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 36261MC ![]() 8j9nC ![]() 8j9oC ![]() 8jh7C ![]() 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 ![]() |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() ![]() |
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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.) ![]() ![]() |
#3: Protein | Mass: 8417.766 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#4: Protein | Mass: 14845.516 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#5: Protein | Mass: 61912.398 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-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: FZD6-Gs complex with Nb35. / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT | ||||||||||||||||
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Source (natural) | Organism: ![]() | ||||||||||||||||
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 |
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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: ![]() |
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) |
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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 | ||||||||||||||||||||||||
Refine LS restraints |
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