[English] 日本語
Yorodumi
- EMDB-36112: Cryo-EM structure of inactive FZD1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-36112
TitleCryo-EM structure of inactive FZD1
Map data
Sample
  • Complex: Frizzled-1 with ICL3-BRIL complex with anti-BRIL Fab
    • Protein or peptide: Frizzled-1,Soluble cytochrome b562
    • Protein or peptide: anti-BRIL Fab Heavy Chain
    • Protein or peptide: anti-Fab nanobody
    • Protein or peptide: anti-BRIL Fab Light Chain
KeywordsFrizzled / class-F / FZD1 / Complex / MEMBRANE PROTEIN
Function / homology
Function and homology information


: / muscular septum morphogenesis / regulation of mesenchymal stem cell differentiation / autocrine signaling / planar cell polarity pathway involved in neural tube closure / astrocyte-dopaminergic neuron signaling / canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation / hard palate development / Wnt receptor activity / membranous septum morphogenesis ...: / muscular septum morphogenesis / regulation of mesenchymal stem cell differentiation / autocrine signaling / planar cell polarity pathway involved in neural tube closure / astrocyte-dopaminergic neuron signaling / canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation / hard palate development / Wnt receptor activity / membranous septum morphogenesis / non-canonical Wnt signaling pathway / 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 / outflow tract morphogenesis / regulation of presynapse assembly / negative regulation of BMP signaling pathway / 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 / negative regulation of canonical Wnt signaling pathway / neuron differentiation / positive regulation of neuron projection development / positive regulation of DNA-binding transcription factor activity / cell-cell signaling / electron transfer activity / periplasmic space / response to xenobiotic stimulus / positive regulation of protein phosphorylation / iron ion binding / signaling receptor binding / focal adhesion / negative regulation of DNA-templated transcription / heme binding / positive regulation of DNA-templated transcription / cell surface / plasma membrane
Similarity search - Function
Frizzled/Smoothened, transmembrane domain / Frizzled/Smoothened family membrane region / Frizzled/Smoothened family membrane region / Frizzled/secreted frizzled-related protein / Frizzled / Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain / Frizzled (fz) domain profile. / GPCR, family 2-like ...Frizzled/Smoothened, transmembrane domain / Frizzled/Smoothened family membrane region / Frizzled/Smoothened family membrane region / Frizzled/secreted frizzled-related protein / Frizzled / Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain / Frizzled (fz) domain profile. / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562
Similarity search - Domain/homology
Soluble cytochrome b562 / Frizzled-1
Similarity search - Component
Biological speciesHomo sapiens (human) / Mus (mice) / Vicugna pacos (alpaca)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsLin X / Xu F
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: 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
DepositionMay 4, 2023-
Header (metadata) releaseJan 17, 2024-
Map releaseJan 17, 2024-
UpdateJan 17, 2024-
Current statusJan 17, 2024Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_36112.png

Downloads & links

-
Map

FileDownload / File: emd_36112.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.832 Å
Density
Contour LevelBy AUTHOR: 0.0142
Minimum - Maximum-0.0017670192 - 2.2508256
Average (Standard dev.)0.0012395822 (±0.024866771)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions288288288
Spacing288288288
CellA=B=C: 239.616 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: #1

Fileemd_36112_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_36112_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_36112_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Frizzled-1 with ICL3-BRIL complex with anti-BRIL Fab

EntireName: Frizzled-1 with ICL3-BRIL complex with anti-BRIL Fab
Components
  • Complex: Frizzled-1 with ICL3-BRIL complex with anti-BRIL Fab
    • Protein or peptide: Frizzled-1,Soluble cytochrome b562
    • Protein or peptide: anti-BRIL Fab Heavy Chain
    • Protein or peptide: anti-Fab nanobody
    • Protein or peptide: anti-BRIL Fab Light Chain

-
Supramolecule #1: Frizzled-1 with ICL3-BRIL complex with anti-BRIL Fab

SupramoleculeName: Frizzled-1 with ICL3-BRIL complex with anti-BRIL Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Frizzled-1,Soluble cytochrome b562

MacromoleculeName: Frizzled-1,Soluble cytochrome b562 / type: protein_or_peptide / ID: 1 / Details: inactive FZD1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 75.034164 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: 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

MacromoleculeName: anti-BRIL Fab Heavy Chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus (mice)
Molecular weightTheoretical: 28.03542 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: 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

MacromoleculeName: anti-Fab nanobody / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Vicugna pacos (alpaca)
Molecular weightTheoretical: 13.390644 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
GSQVQLQESG GGLVQPGGSL RLSCAASGRT ISRYAMSWFR QAPGKEREFV AVARRSGDGA FYADSVQGRF TVSRDDAKNT VYLQMNSLK PEDTAVYYCA IDSDTFYSGS YDYWGQGTQV TVSS

-
Macromolecule #4: anti-BRIL Fab Light Chain

MacromoleculeName: anti-BRIL Fab Light Chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus (mice)
Molecular weightTheoretical: 24.557408 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: 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

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: OTHER
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.7000000000000001 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: NONE
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 327768
FSC plot (resolution estimation)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more