+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36112 | |||||||||
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Title | Cryo-EM structure of inactive FZD1 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Frizzled / class-F / FZD1 / 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 / Wnt receptor activity / non-canonical Wnt signaling pathway / membranous septum morphogenesis ...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 / Wnt receptor activity / non-canonical Wnt signaling pathway / membranous septum morphogenesis / presynapse assembly / Wnt-protein binding / endothelial cell differentiation / midbrain dopaminergic neuron differentiation / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / frizzled binding / PCP/CE pathway / Wnt signalosome / Class B/2 (Secretin family receptors) / Disassembly of the destruction complex and recruitment of AXIN to the membrane / negative regulation of BMP signaling pathway / outflow tract morphogenesis / regulation of presynapse assembly / canonical Wnt signaling pathway / positive regulation of osteoblast differentiation / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / PDZ domain binding / G protein-coupled receptor activity / electron transport chain / positive regulation of DNA-binding transcription factor activity / negative regulation of canonical Wnt signaling pathway / neuron differentiation / positive regulation of neuron projection development / cell-cell signaling / periplasmic space / electron transfer activity / positive regulation of protein phosphorylation / response to xenobiotic stimulus / iron ion binding / focal adhesion / signaling receptor binding / negative regulation of DNA-templated transcription / heme binding / positive regulation of DNA-templated transcription / cell surface / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus (mice) / Vicugna pacos (alpaca) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 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_36112.map.gz | 80.2 MB | EMDB map data format | |
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Header (meta data) | emd-36112-v30.xml emd-36112.xml | 19.1 KB 19.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36112_fsc.xml | 10.8 KB | Display | FSC data file |
Images | emd_36112.png | 40.4 KB | ||
Filedesc metadata | emd-36112.cif.gz | 6.2 KB | ||
Others | emd_36112_additional_1.map.gz emd_36112_half_map_1.map.gz emd_36112_half_map_2.map.gz | 85.8 MB 84.7 MB 84.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36112 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36112 | HTTPS FTP |
-Validation report
Summary document | emd_36112_validation.pdf.gz | 839.7 KB | Display | EMDB validaton report |
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Full document | emd_36112_full_validation.pdf.gz | 839.2 KB | Display | |
Data in XML | emd_36112_validation.xml.gz | 17.7 KB | Display | |
Data in CIF | emd_36112_validation.cif.gz | 22.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36112 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36112 | 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 (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_36112.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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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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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_36112_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36112_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-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: Homo sapiens (human) |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 75.034164 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 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: Frizzled-1, Soluble cytochrome b562, Frizzled-1 |
-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: Mus (mice) |
Molecular weight | Theoretical: 28.03542 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
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: Vicugna pacos (alpaca) |
Molecular weight | Theoretical: 13.390644 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
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: Mus (mice) |
Molecular weight | Theoretical: 24.557408 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
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 | 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 |