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Open data
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Basic information
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Title | FZD6 Gs complex | |||||||||
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![]() | FZD6 / Complex. / MEMBRANE PROTEIN | |||||||||
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 / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / bone development / Activation of the phototransduction cascade / cytoplasmic vesicle membrane / negative regulation of canonical Wnt signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / negative regulation of DNA-binding transcription factor activity / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / platelet activation / 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 / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / 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 / 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 / G protein-coupled receptor signaling pathway / apical plasma membrane / lysosomal membrane / GTPase activity / ubiquitin protein ligase binding / synapse / protein-containing complex binding / endoplasmic reticulum membrane / GTP binding / cell surface / signal transduction / extracellular exosome / membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
![]() | Xu F / Zhang Z | |||||||||
Funding support | 1 items
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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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 80.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.4 KB 20.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.8 KB | Display | ![]() |
Images | ![]() | 44.7 KB | ||
Filedesc metadata | ![]() | 6.3 KB | ||
Others | ![]() ![]() ![]() | 45.1 MB 84.7 MB 84.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 873.5 KB | Display | ![]() |
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Full document | ![]() | 873.1 KB | Display | |
Data in XML | ![]() | 17.8 KB | Display | |
Data in CIF | ![]() | 22.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8jhbMC ![]() 8j9nC ![]() 8j9oC ![]() 8jh7C ![]() 8jhcC ![]() 8jhiC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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
-Additional map: #1
File | emd_36261_additional_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_36261_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36261_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : FZD6-Gs complex with Nb35.
Entire | Name: FZD6-Gs complex with Nb35. |
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Components |
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-Supramolecule #1: FZD6-Gs complex with Nb35.
Supramolecule | Name: FZD6-Gs complex with Nb35. / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-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: ![]() |
Molecular weight | Theoretical: 31.117201 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: HHHHHHENLY FQGSKTEDKR AQKRAEKKRS KLIDKQLQDE KMGYMCTHRL LLLGADNSGK STIVKQMRIL HGGSGGSGGT SGIFETKFQ VDKVNFHMFD VGGQRDERRK WIQCFNDVTA IIFVVDSSDY GSGGSGAGSA NRLQEALNLF KSIWNNRWLR T ISVILFLN ...String: HHHHHHENLY FQGSKTEDKR AQKRAEKKRS KLIDKQLQDE KMGYMCTHRL LLLGADNSGK STIVKQMRIL HGGSGGSGGT SGIFETKFQ VDKVNFHMFD VGGQRDERRK WIQCFNDVTA IIFVVDSSDY GSGGSGAGSA NRLQEALNLF KSIWNNRWLR T ISVILFLN KQDLLAEKVL AGKSKIEDYF PEFARYTTPE DATPEPGEDP RVTRAKYFIR DEFLRISTAS GDGRHYCYPH FT CAVDTEN ARRIFNDCRD IIQRMHLRQY ELL UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas, 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: ![]() |
Molecular weight | Theoretical: 37.41693 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN 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: ![]() |
Molecular weight | Theoretical: 8.417766 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MHHHHHHNTA SIAQARKLVE QLKMEANIDR IKVSKAAADL MAYCEAHAKE DPLLTPVPAS ENPFREKKFF CAIL 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: ![]() |
Molecular weight | Theoretical: 14.845516 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MQVQLQESGG GLVQPGGSLR LSCAASGFTF SNYKMNWVRQ APGKGLEWVS DISQSGASIS YTGSVKGRFT ISRDNAKNTL YLQMNSLKP EDTAVYYCAR CPAPFTRDCF DVTSTTYAYR GQGTQVTVSS HHHHHH |
-Macromolecule #5: Frizzled-6
Macromolecule | Name: Frizzled-6 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 61.912398 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDKHHHHHH HSLFTCEPIT VPRCMKMAYN MTFFPNLMGH YDQSIAAVEM EHFLPLANLE CSPNIETFL CKAFVPTCIE QIHVVPPCRK LCEKVYSDCK KLIDTFGIRW PEELECDRLQ YCDETVPVTF DPHTEFLGPQ K KTEQVQRD ...String: MKTIIALSYI FCLVFADYKD DDDKHHHHHH HSLFTCEPIT VPRCMKMAYN MTFFPNLMGH YDQSIAAVEM EHFLPLANLE CSPNIETFL CKAFVPTCIE QIHVVPPCRK LCEKVYSDCK KLIDTFGIRW PEELECDRLQ YCDETVPVTF DPHTEFLGPQ K KTEQVQRD IGFWCPRHLK TSGGQGYKFL GIDQCAPPCP NMYFKSDELE FAKSFIGTVS IFCLCATLFT FLTFLIDVRR FR YPERPII YYSVCYSIVS LMYFIGFLLG DSTACNKADE KLELGDTVVL GSQNKACTVL FMLLYFFTMA GTVWWVILTI TWF LAAGRK WSCEAIEQKA VWFHAVAWGT PGFLTVMLLA MNKVEGDNIS GVCFVGLYDL DASRYFVLLP LCLCVFVGLS LLLA GIISL NHVRQVIQHD GRNQEKLKKF MIRIGVFSGL YLVPLVTLLG CYVYEQVNRI TWEITWVSDH CRQYHIPCPY QAKAK ARPE LALFMIKYLM TLIVGISAVF WVGSKKTCTE WAGFFKRNRK RDPISESRRV LQE UniProtKB: Frizzled-6 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: DIFFRACTION / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |