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Open data
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Basic information
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Title | Cryo-EM structure of inactive FZD1 | |||||||||
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Function / homology | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Lin X / Xu F | |||||||||
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 | ![]() | 80.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.1 KB 19.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.8 KB | Display | ![]() |
Images | ![]() | 40.4 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Others | ![]() ![]() ![]() | 85.8 MB 84.7 MB 84.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8j9oMC ![]() 8j9nC ![]() 8jh7C ![]() 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
File | emd_36112_additional_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
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Density Histograms |
-Half map: #2
File | emd_36112_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Frizzled-1 with ICL3-BRIL complex with anti-BRIL Fab
Entire | Name: Frizzled-1 with ICL3-BRIL complex with anti-BRIL Fab |
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Components |
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-Supramolecule #1: Frizzled-1 with ICL3-BRIL complex with anti-BRIL Fab
Supramolecule | Name: Frizzled-1 with ICL3-BRIL complex with anti-BRIL Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Frizzled-1,Soluble cytochrome b562
Macromolecule | Name: Frizzled-1,Soluble cytochrome b562 / type: protein_or_peptide / ID: 1 / Details: inactive FZD1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 75.034164 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
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 FIRARRQLAD LEDNWETLND NLKVIEKADN AAQVK DALT KMRAAALDAQ KATPPKLEDK SPDSPEMKDF RHGFDILVGQ IDDALKLANE GKVKEAQAAA EQLKTTRNAY IQKYLE RAR STLKEKLEKL MVRIGVFSVL YTVPATIVIA CYFYEQAFRD QWERSWVAQS CKSYAIPCPH LQAGGGAPPH PPMSPDF TV FMIKYLMTLI VGITSGFWIW SGKTLNSWRK FYTRL UniProtKB: ![]() ![]() |
-Macromolecule #2: anti-BRIL Fab Heavy Chain
Macromolecule | Name: anti-BRIL Fab Heavy Chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 28.03542 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MVSAIVLYVL LAAAAHSAFA EISEVQLVES GGGLVQPGGS LRLSCAASGF NVVDFSLHWV RQAPGKGLEW VAYISSSSGS TSYADSVKG RFTISADTSK NTAYLQMNSL RAEDTAVYYC ARWGYWPGEP WWKAFDYWGQ GTLVTVSSAS TKGPSVFPLA P SSKSTSGG ...String: MVSAIVLYVL LAAAAHSAFA EISEVQLVES GGGLVQPGGS LRLSCAASGF NVVDFSLHWV RQAPGKGLEW VAYISSSSGS TSYADSVKG RFTISADTSK NTAYLQMNSL RAEDTAVYYC ARWGYWPGEP WWKAFDYWGQ GTLVTVSSAS TKGPSVFPLA P SSKSTSGG TAALGCLVKD YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY ICNVNHKPSN TK VDKKVEP KSLEVLFQGP HHHHHH |
-Macromolecule #3: anti-Fab nanobody
Macromolecule | Name: anti-Fab nanobody / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 13.390644 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: GSQVQLQESG GGLVQPGGSL RLSCAASGRT ISRYAMSWFR QAPGKEREFV AVARRSGDGA FYADSVQGRF TVSRDDAKNT VYLQMNSLK PEDTAVYYCA IDSDTFYSGS YDYWGQGTQV TVSS |
-Macromolecule #4: anti-BRIL Fab Light Chain
Macromolecule | Name: anti-BRIL Fab Light Chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() ![]() |
Molecular weight | Theoretical: 24.557408 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MVVYISYIYA SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSL QPEDFATYYC QQYLYYSLVT FGQGTKVEIK RTVAAPSVFI FPPSDSQLKS GTASVVCLLN NFYPREAKVQ W KVDNALQS ...String: MVVYISYIYA SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSL QPEDFATYYC QQYLYYSLVT FGQGTKVEIK RTVAAPSVFI FPPSDSQLKS GTASVVCLLN NFYPREAKVQ W KVDNALQS GNSQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRG |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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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 |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |