[English] 日本語
Yorodumi
- EMDB-64380: Structure of the complex of LGR4_ECD with Norrin -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-64380
TitleStructure of the complex of LGR4_ECD with Norrin
Map data
Sample
  • Complex: Structure of the complex of LGR4_ECD with Norrin
    • Protein or peptide: MB52
    • Protein or peptide: Leucine-rich repeat-containing G-protein coupled receptor 4
    • Protein or peptide: Norrin,Immunoglobulin gamma-1 heavy chain
KeywordsLGR4 Norrin / MEMBRANE PROTEIN
Function / homology
Function and homology information


retina blood vessel maintenance / cone retinal bipolar cell differentiation / Norrin signaling pathway / extracellular matrix-cell signaling / retinal rod cell differentiation / re-entry into mitotic cell cycle / retinal blood vessel morphogenesis / metanephric glomerulus development / metanephric nephron tubule morphogenesis / epithelial cell proliferation involved in renal tubule morphogenesis ...retina blood vessel maintenance / cone retinal bipolar cell differentiation / Norrin signaling pathway / extracellular matrix-cell signaling / retinal rod cell differentiation / re-entry into mitotic cell cycle / retinal blood vessel morphogenesis / metanephric glomerulus development / metanephric nephron tubule morphogenesis / epithelial cell proliferation involved in renal tubule morphogenesis / protein-hormone receptor activity / glycine metabolic process / intestinal stem cell homeostasis / retina layer formation / retinal pigment epithelium development / endothelial cell differentiation / microglial cell proliferation / dendritic spine development / negative regulation of toll-like receptor signaling pathway / establishment of blood-retinal barrier / vacuole organization / positive regulation of branching involved in ureteric bud morphogenesis / male genitalia development / microglia differentiation / protein targeting to lysosome / establishment of blood-brain barrier / bone remodeling / frizzled binding / optic nerve development / retinal ganglion cell axon guidance / lens development in camera-type eye / digestive tract development / negative regulation of cold-induced thermogenesis / negative regulation of cytokine production / ubiquitin-dependent endocytosis / smoothened signaling pathway / bone mineralization / exploration behavior / decidualization / action potential / hair follicle development / blood vessel remodeling / immunoglobulin complex / canonical Wnt signaling pathway / response to axon injury / : / tricarboxylic acid cycle / visual perception / transforming growth factor beta receptor signaling pathway / Regulation of FZD by ubiquitination / cytokine activity / glutathione metabolic process / circadian regulation of gene expression / G protein-coupled receptor activity / Wnt signaling pathway / osteoblast differentiation / transmembrane signaling receptor activity / positive regulation of canonical Wnt signaling pathway / nervous system development / mitotic cell cycle / neuron apoptotic process / angiogenesis / spermatogenesis / cellular response to hypoxia / transcription by RNA polymerase II / adaptive immune response / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein ubiquitination / inflammatory response / innate immune response / positive regulation of DNA-templated transcription / cell surface / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / : / extracellular region / plasma membrane
Similarity search - Function
Norrie disease protein / Glycoprotein hormone subunit beta / Cystine-knot domain / Glycoprotein hormone receptor family / C-terminal cystine knot signature. / C-terminal cystine knot domain profile. / Cystine knot, C-terminal / C-terminal cystine knot-like domain (CTCK) / Leucine rich repeat N-terminal domain / Leucine-rich repeat N-terminal domain ...Norrie disease protein / Glycoprotein hormone subunit beta / Cystine-knot domain / Glycoprotein hormone receptor family / C-terminal cystine knot signature. / C-terminal cystine knot domain profile. / Cystine knot, C-terminal / C-terminal cystine knot-like domain (CTCK) / Leucine rich repeat N-terminal domain / Leucine-rich repeat N-terminal domain / Leucine rich repeat N-terminal domain / Leucine Rich Repeat / Leucine-rich repeats, bacterial type / Cystine-knot cytokine / Leucine-rich repeat, SDS22-like subfamily / Leucine rich repeat / Leucine-rich repeat, typical subtype / Leucine-rich repeats, typical (most populated) subfamily / : / Leucine-rich repeat profile. / Leucine-rich repeat / Immunoglobulin V-Type / Immunoglobulin V-set domain / Leucine-rich repeat domain superfamily / Immunoglobulin V-set domain / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / Immunoglobulin subtype / Immunoglobulin / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Immunoglobulin gamma-1 heavy chain / Norrin / Leucine-rich repeat-containing G-protein coupled receptor 4
Similarity search - Component
Biological speciesHomo sapiens (human) / Camelus ferus (Wild Bactrian camel)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.05 Å
AuthorsGeng Y / Hu FZ / Qiao HR
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Nat Commun / Year: 2025
Title: Distinct structural mechanisms of LGR4 modulation by Norrin and RSPOs in Wnt/β-catenin signaling.
Authors: Huarui Qiao / Fangzheng Hu / Yiang Wang / Lu Wang / Siyu Zhou / Shaojue Guo / Yiwen Xu / Jianfeng Xu / Qianqian Cui / Qilun Yang / H Eric Xu / Jianwei Zhu / Yong Geng /
Abstract: The Wnt/β-catenin pathway requires precise regulation for proper development and tissue homeostasis, yet the structural mechanisms enabling its fine-tuned control remain incompletely understood. ...The Wnt/β-catenin pathway requires precise regulation for proper development and tissue homeostasis, yet the structural mechanisms enabling its fine-tuned control remain incompletely understood. Here, we reveal how LGR4 achieves differential signaling outcomes through distinct recognition of two key modulators: Norrin and R-spondins (RSPOs). Using cryo-electron microscopy, we determined the structure of full-length LGR4 bound to Norrin in a 2:2 stoichiometry, revealing a molecular bridging mechanism where Norrin dimer connect two LGR4 protomers in a spatial arrangement fundamentally distinct from the LGR4-RSPO2-ZNRF3 complex. Notably, Norrin binding to LGR4 sterically hinders simultaneous interaction with the Frizzled4 receptor, establishing a regulatory checkpoint in Wnt signaling. The partially overlapping binding sites for Norrin and RSPOs on LGR4 enable mutually exclusive interactions that drive distinct signaling outcomes. Disease-linked mutations map to distinct functional regions: those disrupting LGR4 interaction are associated with familial exudative vitreoretinopathy (FEVR), while others impairing Frizzled4 binding are linked to Norrie disease. Furthermore, we developed a high-affinity nanobody that blocks both Norrin and RSPO binding to LGR4, providing a potential tool for therapeutic intervention. These findings elucidate the structural basis of LGR4's dual signaling roles and lay the groundwork for therapeutic strategies targeting Wnt-related diseases.
History
DepositionApr 25, 2025-
Header (metadata) releaseJul 16, 2025-
Map releaseJul 16, 2025-
UpdateFeb 18, 2026-
Current statusFeb 18, 2026Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_64380.png

Downloads & links

-
Map

FileDownload / File: emd_64380.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 512 pix.
= 548.352 Å		1.07 Å/pix.
x 512 pix.
= 548.352 Å		1.07 Å/pix.
x 512 pix.
= 548.352 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.071 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.172
Minimum - Maximum-1.0869586 - 1.7673945
Average (Standard dev.)-0.00012791506 (±0.0074427007)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 548.352 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Additional map: #1

Fileemd_64380_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_64380_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_64380_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Structure of the complex of LGR4_ECD with Norrin

EntireName: Structure of the complex of LGR4_ECD with Norrin
Components
  • Complex: Structure of the complex of LGR4_ECD with Norrin
    • Protein or peptide: MB52
    • Protein or peptide: Leucine-rich repeat-containing G-protein coupled receptor 4
    • Protein or peptide: Norrin,Immunoglobulin gamma-1 heavy chain

-
Supramolecule #1: Structure of the complex of LGR4_ECD with Norrin

SupramoleculeName: Structure of the complex of LGR4_ECD with Norrin / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: MB52

MacromoleculeName: MB52 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Camelus ferus (Wild Bactrian camel)
Molecular weightTheoretical: 59.266367 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MKKIWLALAG LVLAFSASAQ VQLVESGGGL VQTKTTTSVI DTTNDAQNLL TQAQTIVNTL KDYCPILIAK SSSSNGGTNN ANTPSWQTA GGGKNSCATF GAEFSAASDM INNAQKIVQE TQQLSANQPK NITQPHNLNL NSPSSLTALA QKMLKNAQSQ A EILKLANQ ...String:
MKKIWLALAG LVLAFSASAQ VQLVESGGGL VQTKTTTSVI DTTNDAQNLL TQAQTIVNTL KDYCPILIAK SSSSNGGTNN ANTPSWQTA GGGKNSCATF GAEFSAASDM INNAQKIVQE TQQLSANQPK NITQPHNLNL NSPSSLTALA QKMLKNAQSQ A EILKLANQ VESDFNKLSS GHLKDYIGKC DASAISSANM TMQNQKNNWG NGCAGVEETQ SLLKTSAADF NNQTPQINQA QN LANTLIQ ELGNNPFRAS GGGSGGGGSG KLSDTYEQLS RLLTNDNGTN SKTSAQAINQ AVNNLNERAK TLAGGTTNSP AYQ ATLLAL RSVLGLWNSM GYAVICGGYT KSPGENNQKD FHYTDENGNG TTINCGGSTN SNGTHSYNGT NTLKADKNVS LSIE QYEKI HEAYQILSKA LKQAGLAPLN SKGEKLEAHV TTSKYGSLRL SCAASGYTYS PYCMGWFRQA PGKAREGVAT VDLDG STIY ADSVKGRFTI SQDNAKNTLY LQMNSLKPED TAMYYCASRT RAGVTCGLNW AIFSYWGQGT QVTVSSHHHH HH

-
Macromolecule #2: Leucine-rich repeat-containing G-protein coupled receptor 4

MacromoleculeName: Leucine-rich repeat-containing G-protein coupled receptor 4
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 105.397508 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKTIIALSYI FCLVFAAPPL CAAPCSCDGD RRVDCSGKGL TAVPEGLSAF TQALDISMNN ITQLPEDAFK NFPFLEELQL AGNDLSFIH PKALSGLKEL KVLTLQNNQL KTVPSEAIRG LSALQSLRLD ANHITSVPED SFEGLVQLRH LWLDDNSLTE V PVHPLSNL ...String:
MKTIIALSYI FCLVFAAPPL CAAPCSCDGD RRVDCSGKGL TAVPEGLSAF TQALDISMNN ITQLPEDAFK NFPFLEELQL AGNDLSFIH PKALSGLKEL KVLTLQNNQL KTVPSEAIRG LSALQSLRLD ANHITSVPED SFEGLVQLRH LWLDDNSLTE V PVHPLSNL PTLQALTLAL NKISSIPDFA FTNLSSLVVL HLHNNKIRSL SQHCFDGLDN LETLDLNYNN LGEFPQAIKA LP SLKELGF HSNSISVIPD GAFDGNPLLR TIHLYDNPLS FVGNSAFHNL SDLHSLVIRG ASMVQQFPNL TGTVHLESLT LTG TKISSI PNNLCQEQKM LRTLDLSYNN IRDLPSFNGC HALEEISLQR NQIYQIKEGT FQGLISLRIL DLSRNLIHEI HSRA FATLG PITNLDVSFN ELTSFPTEGL NGLNQLKLVG NFKLKEALAA KDFVNLRSLS VPYAYQCCAF WGCDSYANLN TEDNS LQDH SVAQEKGTAD AANVTSTLEN EEHSQIIIHC TPSTGAFKPC EYLLGSWMIR LTVWFIFLVA LFFNLLVILT TFASCT SLP SSKLFIGLIS VSNLFMGIYT GILTFLDAVS WGRFAEFGIW WETGSGCKVA GFLAVFSSES AIFLLMLATV ERSLSAK DI MKNGKSNHLK QFRVAALLAF LGATVAGCFP LFHRGEYSAS PLCLPFPTGE TPSLGFTVTL VLLNSLAFLL MAVIYTKL Y CNLEKEDLSE NSQSSMIKHV AWLIFTNCIF FCPVAFFSFA PLITAISISP EIMKSVTLIF FPLPACLNPV LYVFFNPKF KEDWKLLKRR VTKKSGSVSV SISSQGGCLE QDFYYDCGMY SHLQGNLTVC DCCESFLLTK PVSCKHLIKS HSCPALAVAS CQRPEGYWS DCGTQSAHSD YADEEDSFVS DSSDQVQACG RACFYQSRGF PLVRYAYNLP RVKDAAADYK DDDDK

UniProtKB: Leucine-rich repeat-containing G-protein coupled receptor 4

-
Macromolecule #3: Norrin,Immunoglobulin gamma-1 heavy chain

MacromoleculeName: Norrin,Immunoglobulin gamma-1 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 45.313438 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAKT DSSFIMDSDP RRCMRHHYVD SISHPLYKCS SKMVLLARCE GHCSQASRS EPLVSFSTVL KQPFRSSCHC CRPQTSKLKA LRLRCSGGMR LTATYRYILS CHCEECNSGG SGGSGGLEVL F QGPGGSGG ...String:
MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAKT DSSFIMDSDP RRCMRHHYVD SISHPLYKCS SKMVLLARCE GHCSQASRS EPLVSFSTVL KQPFRSSCHC CRPQTSKLKA LRLRCSGGMR LTATYRYILS CHCEECNSGG SGGSGGLEVL F QGPGGSGG SGGKSCDKTH TCPPCPAPEL LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HN AKTKPRE EQYNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKALPAPIE KTISKAKGQP REPQVYTLPP SRDELTKNQV SLT CLVKGF YPSDIAVEWE SNGQPENNYK ATPPVLDSDG SFFLYSKLTV DKSRWQQGNV FSCSVMHEAL HNHYTQKSLS LSPG KDYKD DDDK

UniProtKB: Norrin, Immunoglobulin gamma-1 heavy chain

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 70.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING ONLY
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.05 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1196610
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
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