+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36266 | |||||||||
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Title | FZD3-Gs complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | FZD3 / Complex / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information dopaminergic neuron axon guidance / serotonergic neuron axon guidance / cell proliferation in midbrain / establishment of planar polarity / negative regulation of mitotic cell cycle, embryonic / Wnt receptor activity / midbrain morphogenesis / non-canonical Wnt signaling pathway / motor neuron migration / sympathetic ganglion development ...dopaminergic neuron axon guidance / serotonergic neuron axon guidance / cell proliferation in midbrain / establishment of planar polarity / negative regulation of mitotic cell cycle, embryonic / Wnt receptor activity / midbrain morphogenesis / non-canonical Wnt signaling pathway / motor neuron migration / sympathetic ganglion development / sensory perception of chemical stimulus / filopodium tip / Wnt-protein binding / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / post-anal tail morphogenesis / negative regulation of execution phase of apoptosis / commissural neuron axon guidance / 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 / presynaptic active zone / PKA activation in glucagon signalling / hair follicle development / developmental growth / D1 dopamine receptor binding / canonical Wnt signaling pathway / lateral plasma membrane / Hedgehog 'off' state / response to electrical stimulus / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / adenylate cyclase activator activity / Asymmetric localization of PCP proteins / neural tube closure / PDZ domain binding / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / 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 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / neuron differentiation / 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 / 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 / response to xenobiotic stimulus / apical plasma membrane / G protein-coupled receptor signaling pathway / lysosomal membrane / axon Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Xu F / Zhang Z | |||||||||
Funding support | 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36266.map.gz | 85.8 MB | EMDB map data format | |
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Header (meta data) | emd-36266-v30.xml emd-36266.xml | 18.4 KB 18.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36266_fsc.xml | 9.6 KB | Display | FSC data file |
Images | emd_36266.png | 77.7 KB | ||
Masks | emd_36266_msk_1.map | 91.1 MB | Mask map | |
Filedesc metadata | emd-36266.cif.gz | 6.3 KB | ||
Others | emd_36266_half_map_1.map.gz emd_36266_half_map_2.map.gz | 84.5 MB 84.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36266 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36266 | HTTPS FTP |
-Related structure data
Related structure data | 8jhiMC 8j9nC 8j9oC 8jh7C 8jhbC 8jhcC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_36266.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_36266_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36266_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36266_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of FZD3-Gs heterotrimer with Nb35.
Entire | Name: Complex of FZD3-Gs heterotrimer with Nb35. |
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Components |
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-Supramolecule #1: Complex of FZD3-Gs heterotrimer with Nb35.
Supramolecule | Name: Complex of FZD3-Gs heterotrimer with Nb35. / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
Macromolecule | Name: Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas type: protein_or_peptide / ID: 1 / Details: minGas / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 28.861875 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: NSKTEDKRAQ KRAEKKRSKL IDKQLQDEKM GYMCTHRLLL LGADNSGKST IVKQMRILHG GSGGSGGTSG IFETKFQVDK VNFHMFDVG GQRDERRKWI QCFNDVTAII FVVDSSDYNR LQEALNLFKS IWNNRWLRTI SVILFLNKQD LLAEKVLAGK S KIEDYFPE ...String: NSKTEDKRAQ KRAEKKRSKL IDKQLQDEKM GYMCTHRLLL LGADNSGKST IVKQMRILHG GSGGSGGTSG IFETKFQVDK VNFHMFDVG GQRDERRKWI QCFNDVTAII FVVDSSDYNR LQEALNLFKS IWNNRWLRTI SVILFLNKQD LLAEKVLAGK S KIEDYFPE FARYTTPEDA TPEPGEDPRV TRAKYFIRDE FLRISTASGD GRHYCYPHFT CAVDTENARR IFNDCRDIIQ RM HLRQYEL L UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas, Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 37.069543 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVSA SQDGKLIIWD SYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH TGYLSCCRFL DDNQIVTSSG D TTCALWDI ...String: LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVSA SQDGKLIIWD SYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH TGYLSCCRFL DDNQIVTSSG D TTCALWDI ETGQQTTTFT GHTGDVMSLS LAPDTRLFVS GACDASAKLW DVREGMCRQT FTGHESDINA ICFFPNGNAF AT GSDDATC RLFDLRADQE LMTYSHDNII CGITSVSFSK SGRLLLAGYD DFNCNVWDAL KADRAGVLAG HDNRVSCLGV TDD GMAVAT GSWDSFLKIW N UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 6.261229 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: TASIAQARKL VEQLKMEANI DRIKVSKAAA DLMAYCEAHA KEDPLLTPVP ASENPFR UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #4: Nb35
Macromolecule | Name: Nb35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.711284 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTV |
-Macromolecule #5: Frizzled-3
Macromolecule | Name: Frizzled-3 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 60.076348 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: HSLFSCEPIT LRMCQDLPYN TTFMPNLLNH YDQQTAALAM EPFHPMVNLD CSRDFRPFLC ALYAPICMEY GRVTLPCRRL CQRAYSECS KLMEMFGVPW PEDMECSRFP DCDEPYPRLV DLNLAGEPTE GAPVAVQRDY GFWCPRELKI DPDLGYSFLH V RDCSPPCP ...String: HSLFSCEPIT LRMCQDLPYN TTFMPNLLNH YDQQTAALAM EPFHPMVNLD CSRDFRPFLC ALYAPICMEY GRVTLPCRRL CQRAYSECS KLMEMFGVPW PEDMECSRFP DCDEPYPRLV DLNLAGEPTE GAPVAVQRDY GFWCPRELKI DPDLGYSFLH V RDCSPPCP NMYFRREELS FARYFIGLIS IICLSATLFT FLTFLIDVTR FRYPERPIIF YAVCYMMVSL IFFIGFLLED RV ACNASIP AQYKASTVTQ GSHNKACTML FMILYFFTMA GSVWWVILTI TWFLAAVPKW GSEAIEKKAL LFHASAWGIP GTL TIILLA MNKIEGDNIS GVCFVGLYDV DALRYFVLAP LCLYVVVGVS LLLAGIISLN RVRIEIPLEK ENQDKLVKFM IRIG VFSIL YLVPLLVVIG CYFYEQAYRG IWETTWIQER CREYHIPCPY QVTQMSRPDL ILFLMKYLMA LIVGIPSVFW VGSKK TCFE WASFFHGRRK KEIVNESRQV LQEPDFAQSL LRDPNT UniProtKB: Frizzled-3 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: DIFFRACTION / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 20.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |