+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 / PKA activation in glucagon signalling / Wnt receptor activity / midbrain morphogenesis / motor neuron migration / non-canonical Wnt signaling pathway ...dopaminergic neuron axon guidance / serotonergic neuron axon guidance / cell proliferation in midbrain / establishment of planar polarity / negative regulation of mitotic cell cycle, embryonic / PKA activation in glucagon signalling / Wnt receptor activity / midbrain morphogenesis / motor neuron migration / non-canonical Wnt signaling pathway / sympathetic ganglion development / filopodium tip / sensory perception of chemical stimulus / Wnt-protein binding / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / post-anal tail morphogenesis / negative regulation of execution phase of apoptosis / commissural neuron axon guidance / Hedgehog 'off' state / 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 / adenylate cyclase activator activity / presynaptic active zone / hair follicle development / lateral plasma membrane / canonical Wnt signaling pathway / response to electrical stimulus / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / bone development / G-protein beta/gamma-subunit complex binding / platelet aggregation / neural tube closure / Asymmetric localization of PCP proteins / G protein-coupled receptor activity / PDZ domain binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuron differentiation / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / positive regulation of cold-induced thermogenesis / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / 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 / G protein-coupled receptor signaling pathway / apical plasma membrane / lysosomal membrane 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 |
-Validation report
Summary document | emd_36266_validation.pdf.gz | 1.2 MB | Display | EMDB validaton report |
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Full document | emd_36266_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | emd_36266_validation.xml.gz | 18 KB | Display | |
Data in CIF | emd_36266_validation.cif.gz | 23.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36266 ftp://ftp.pdbj.org/pub/emdb/validation_reports/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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 20.0 e/Å2 |
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 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |