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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | FZD6 in inactive state | |||||||||
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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 / Wnt receptor activity / midbrain morphogenesis / non-canonical Wnt signaling pathway / Wnt-protein binding / apicolateral plasma membrane / PCP/CE pathway ...embryonic nail plate morphogenesis / establishment of body hair planar orientation / cell proliferation in midbrain / Signaling by RNF43 mutants / Wnt receptor activity / midbrain morphogenesis / non-canonical Wnt signaling pathway / Wnt-protein binding / apicolateral plasma membrane / PCP/CE pathway / Class B/2 (Secretin family receptors) / Wnt signaling pathway, planar cell polarity pathway / hair follicle development / inner ear morphogenesis / canonical Wnt signaling pathway / Regulation of FZD by ubiquitination / neural tube closure / G protein-coupled receptor activity / electron transport chain / negative regulation of canonical Wnt signaling pathway / cytoplasmic vesicle membrane / negative regulation of DNA-binding transcription factor activity / platelet activation / Ca2+ pathway / periplasmic space / electron transfer activity / apical plasma membrane / iron ion binding / ubiquitin protein ligase binding / endoplasmic reticulum membrane / heme binding / cell surface / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Xu F / Zhang Z | |||||||||
Funding support | ![]()
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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 | ![]() | 109 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.1 KB 19.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.7 KB | Display | ![]() |
Images | ![]() | 54.8 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Others | ![]() ![]() ![]() | 62.1 MB 116.1 MB 116.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 809.9 KB | Display | ![]() |
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Full document | ![]() | 809.4 KB | Display | |
Data in XML | ![]() | 18.8 KB | Display | |
Data in CIF | ![]() | 23.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8jh7MC ![]() 8j9nC ![]() 8j9oC ![]() 8jhbC ![]() 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
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Density Histograms |
-Half map: #2
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-Half map: #1
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Sample components
-Entire : Complex of human FZD6 in inactivate state with accessory proteins.
Entire | Name: Complex of human FZD6 in inactivate state with accessory proteins. |
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Components |
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-Supramolecule #1: Complex of human FZD6 in inactivate state with accessory proteins.
Supramolecule | Name: Complex of human FZD6 in inactivate state with accessory proteins. type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: anti-BRIL Fab Heavy chain
Macromolecule | Name: anti-BRIL Fab Heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.704648 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EVQLVESGGG LVQPGGSLRL SCAASGFNVV DFSLHWVRQA PGKGLEWVAY ISSSSGSTSY ADSVKGRFTI SADTSKNTAY LQMNSLRAE DTAVYYCARW GYWPGEPWWK AFDYWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ...String: EVQLVESGGG LVQPGGSLRL SCAASGFNVV DFSLHWVRQA PGKGLEWVAY ISSSSGSTSY ADSVKGRFTI SADTSKNTAY LQMNSLRAE DTAVYYCARW GYWPGEPWWK AFDYWGQGTL VTVSSASTKG PSVFPLAPSS KSTSGGTAAL GCLVKDYFPE P VTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSLE VLFQGPHHHH HH |
-Macromolecule #2: anti-Fab Nanobody
Macromolecule | Name: anti-Fab Nanobody / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 14.075395 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: HHHHHHQVQL QESGGGLVQP GGSLRLSCAA SGRTISRYAM SWFRQAPGKE REFVAVARRS GDGAFYADSV QGRFTVSRDD AKNTVYLQM NSLKPEDTAV YYCAIDSDTF YSGSYDYWGQ GTQVTVSS |
-Macromolecule #3: anti-BRIL Fab Light chain
Macromolecule | Name: anti-BRIL Fab Light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.20982 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DIQMTQSPSS LSASVGDRVT ITCRASQSVS SAVAWYQQKP GKAPKLLIYS ASSLYSGVPS RFSGSRSGTD FTLTISSLQP EDFATYYCQ QYLYYSLVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: DIQMTQSPSS LSASVGDRVT ITCRASQSVS SAVAWYQQKP GKAPKLLIYS ASSLYSGVPS RFSGSRSGTD FTLTISSLQP EDFATYYCQ QYLYYSLVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNR |
-Macromolecule #4: Frizzled-6,Soluble cytochrome b562
Macromolecule | Name: Frizzled-6,Soluble cytochrome b562 / type: protein_or_peptide / ID: 4 / Details: inactive FZD6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 73.464352 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDKHHHHHH HHHHENLYFQ GHSLFTCEPI TVPRCMKMAY NMTFFPNLMG HYDQSIAAVE MEHFLPLAN LECSPNIETF LCKAFVPTCI EQIHVVPPCR KLCEKVYSDC KKLIDTFGIR WPEELECDRL QYCDETVPVT F DPHTEFLG ...String: MKTIIALSYI FCLVFADYKD DDDKHHHHHH HHHHENLYFQ GHSLFTCEPI TVPRCMKMAY NMTFFPNLMG HYDQSIAAVE MEHFLPLAN LECSPNIETF LCKAFVPTCI EQIHVVPPCR KLCEKVYSDC KKLIDTFGIR WPEELECDRL QYCDETVPVT F DPHTEFLG PQKKTEQVQR DIGFWCPRHL KTSGGQGYKF LGIDQCAPPC PNMYFKSDEL EFAKSFIGTV SIFCLCATLF TF LTFLIDV RRFRYPERPI IYYSVCYSIV SLMYFIGFLL GDSTACNKAD EKLELGDTVV LGSQNKACTV LFMLLYFFTM AGT VWWVIL TITWFLAAGR KWSCEAIEQK AVWFHAVAWG TPGFLTVMLL AMNKVEGDNI SGVCFVGLYD LDASRYFVLL PLCL CVFVG LSLLLAGIIS LNHVARRQLA DLEDNWETLN DNLKVIEKAD NAAQVKDALT KMRAAALDAQ KATPPKLEDK SPDSP EMKD FRHGFDILVG QIDDALKLAN EGKVKEAQAA AEQLKTTRNA YIQKYLERAR STLEEKLKKF MIRIGVFSGL YLVPLV TLL GCYVYEQVNR ITWEITWVSD HCRQYHIPCP YQAKAKARPE LALFMIKYLM TLIVGISAVF WVGSKKTCTE WAGFFKR N UniProtKB: Frizzled-6, Soluble cytochrome b562, 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: OTHER / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |