+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36111 | |||||||||
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Title | Gq bound FZD1 in ligand-free state | |||||||||
Map data | ||||||||||
Sample |
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Keywords | FZD1-Gq / class-F / Frizzled receptor / Complex / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information muscular septum morphogenesis / regulation of mesenchymal stem cell differentiation / autocrine signaling / : / astrocyte-dopaminergic neuron signaling / canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation / hard palate development / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / Wnt receptor activity ...muscular septum morphogenesis / regulation of mesenchymal stem cell differentiation / autocrine signaling / : / astrocyte-dopaminergic neuron signaling / canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation / hard palate development / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / Wnt receptor activity / membranous septum morphogenesis / presynapse assembly / non-canonical Wnt signaling pathway / PLC beta mediated events / entrainment of circadian clock / Wnt-protein binding / phospholipase C-activating dopamine receptor signaling pathway / endothelial cell differentiation / midbrain dopaminergic neuron differentiation / regulation of platelet activation / phototransduction, visible light / frizzled binding / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / PCP/CE pathway / Class B/2 (Secretin family receptors) / Wnt signalosome / glutamate receptor signaling pathway / regulation of canonical Wnt signaling pathway / Disassembly of the destruction complex and recruitment of AXIN to the membrane / outflow tract morphogenesis / action potential / regulation of presynapse assembly / negative regulation of BMP signaling pathway / photoreceptor outer segment / canonical Wnt signaling pathway / positive regulation of osteoblast differentiation / GTPase activator activity / G-protein beta/gamma-subunit complex binding / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / G protein-coupled receptor binding / G protein-coupled receptor activity / PDZ domain binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of DNA-binding transcription factor activity / negative regulation of protein kinase activity / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / negative regulation of canonical Wnt signaling pathway / 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 / neuron differentiation / 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 / positive regulation of neuron projection development / 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 / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / blood coagulation / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / cell-cell signaling / 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 / nuclear membrane / Ras protein signal transduction Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Vicugna pacos (alpaca) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Lin X / Xu F | |||||||||
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_36111.map.gz | 49.3 MB | EMDB map data format | |
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Header (meta data) | emd-36111-v30.xml emd-36111.xml | 20.7 KB 20.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36111_fsc.xml | 8.1 KB | Display | FSC data file |
Images | emd_36111.png | 33.6 KB | ||
Filedesc metadata | emd-36111.cif.gz | 6.5 KB | ||
Others | emd_36111_additional_1.map.gz emd_36111_half_map_1.map.gz emd_36111_half_map_2.map.gz | 52.3 MB 51.5 MB 51.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36111 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36111 | HTTPS FTP |
-Validation report
Summary document | emd_36111_validation.pdf.gz | 764.7 KB | Display | EMDB validaton report |
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Full document | emd_36111_full_validation.pdf.gz | 764.2 KB | Display | |
Data in XML | emd_36111_validation.xml.gz | 15.6 KB | Display | |
Data in CIF | emd_36111_validation.cif.gz | 20.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36111 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36111 | HTTPS FTP |
-Related structure data
Related structure data | 8j9nMC 8j9oC 8jh7C 8jhbC 8jhcC 8jhiC 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_36111.map.gz / Format: CCP4 / Size: 55.4 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: 1.06 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_36111_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36111_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36111_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : FZD1-Gq complex in the ligand-free state
Entire | Name: FZD1-Gq complex in the ligand-free state |
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Components |
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-Supramolecule #1: FZD1-Gq complex in the ligand-free state
Supramolecule | Name: FZD1-Gq complex in the ligand-free state / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Frizzled-1
Macromolecule | Name: Frizzled-1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 64.015668 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: GVRAQAAGQG PGQGPGPGQQ PPPPPQQQQS GQQYNGERGI SVPDHGYCQP ISIPLCTDIA YNQTIMPNLL GHTNQEDAGL EVHQFYPLV KVQCSAELKF FLCSMYAPVC TVLEQALPPC RSLCERARQG CEALMNKFGF QWPDTLKCEK FPVHGAGELC V GQNTSDKG ...String: GVRAQAAGQG PGQGPGPGQQ PPPPPQQQQS GQQYNGERGI SVPDHGYCQP ISIPLCTDIA YNQTIMPNLL GHTNQEDAGL EVHQFYPLV KVQCSAELKF FLCSMYAPVC TVLEQALPPC RSLCERARQG CEALMNKFGF QWPDTLKCEK FPVHGAGELC V GQNTSDKG TPTPSLLPEF WTSNPQHGGG GHRGGFPGGA GASERGKFSC PRALKVPSYL NYHFLGEKDC GAPCEPTKVY GL MYFGPEE LRFSRTWIGI WSVLCCASTL FTVLTYLVDM RRFSYPERPI IFLSGCYTAV AVAYIAGFLL EDRVVCNDKF AED GARTVA QGTKKEGCTI LFMMLYFFSM ASSIWWVILS LTWFLAAGMK WGHEAIEANS QYFHLAAWAV PAIKTITILA LGQV DGDVL SGVCFVGLNN VDALRGFVLA PLFVYLFIGT SFLLAGFVSL FRIRTIMKHD GTKTEKLEKL MVRIGVFSVL YTVPA TIVI ACYFYEQAFR DQWERSWVAQ SCKSYAIPCP HLQAGGGAPP HPPMSPDFTV FMIKYLMTLI VGITSGFWIW SGKTLN SWR KFYTRLTNSK QGETTV UniProtKB: Frizzled-1 |
-Macromolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
Macromolecule | Name: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Guanine nucleotide-binding protein G(q) subunit alpha type: protein_or_peptide / ID: 2 / Details: Chimeric protein MiniGQ / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 28.8205 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: GNSKTEDQRN EEKAQREANK KIEQLRRDKR DARRATHRLL LLGADNSGKS TIVKQMRILH GGSGGSGGTS GIFETKFQVD KVNFHMFDV GGQRDERRKW IQCFNDVTAI IFVVDSSDYN RLQEALNLFK SIWNNRWLRT ISVILFLNKQ DLLAEKVLAG K SKIEDYFP ...String: GNSKTEDQRN EEKAQREANK KIEQLRRDKR DARRATHRLL LLGADNSGKS TIVKQMRILH GGSGGSGGTS GIFETKFQVD KVNFHMFDV GGQRDERRKW IQCFNDVTAI IFVVDSSDYN RLQEALNLFK SIWNNRWLRT ISVILFLNKQ DLLAEKVLAG K SKIEDYFP EFARYTTPED ATPEPGEDPR VTRAKYFIRD EFLRISTASG DGRHYCYPHF TCAVDTENAR RIFNDCKDTI LQ LNLKEYN LV UniProtKB: UNIPROTKB: P63092, Guanine nucleotide-binding protein G(q) subunit alpha, UNIPROTKB: P63092, UNIPROTKB: P63092, Guanine nucleotide-binding protein G(q) subunit alpha |
-Macromolecule #3: 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: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 37.41693 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
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 #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 7.845078 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFSAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #5: nanobody Nb35
Macromolecule | Name: nanobody Nb35 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Vicugna pacos (alpaca) |
Molecular weight | Theoretical: 16.054232 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MKYLLPTAAA GLLLLAAQPA MAMQVQLQES GGGLVQPGGS LRLSCAASGF TFSNYKMNWV RQAPGKGLEW VSDISQSGAS ISYTGSVKG RFTISRDNAK NTLYLQMNSL KPEDTAVYYC ARCPAPFTRD CFDVTSTTYA YRGQGTQVTV |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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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: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: OTHER |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.7000000000000001 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |