[English] 日本語
Yorodumi
- EMDB-53437: The structure of ADGRL4 in the active-state -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-53437
TitleThe structure of ADGRL4 in the active-state
Map data
Sample
  • Complex: ADGRL4 complex
    • Complex: Adhesion G protein-coupled receptor L4
      • Protein or peptide: Green fluorescent protein,Adhesion G protein-coupled receptor L4
    • Complex: mini-Gq
      • Protein or peptide: GNAS complex locus,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
    • Complex: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Complex: G-subunit gamma-2
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
KeywordsAdhesion GPCR / ADGRL4 / ELTD1 / MEMBRANE PROTEIN
Function / homology
Function and homology information


PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / intracellular transport / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / activation of adenylate cyclase activity / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway ...PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / intracellular transport / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / activation of adenylate cyclase activity / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of insulin secretion / cellular response to glucagon stimulus / bioluminescence / adenylate cyclase activator activity / trans-Golgi network membrane / generation of precursor metabolites and energy / negative regulation of inflammatory response to antigenic stimulus / bone development / G protein-coupled receptor activity / platelet aggregation / cognition / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / Adrenaline,noradrenaline inhibits insulin secretion / sensory perception of smell / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / sensory perception of taste / positive regulation of cold-induced thermogenesis / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / retina development in camera-type eye / G protein activity / GTPase binding / cytoplasmic vesicle / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / cell surface receptor signaling pathway / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / calcium ion binding / synapse / GTP binding / protein-containing complex binding / signal transduction / extracellular exosome / metal ion binding / membrane / plasma membrane / cytoplasm / cytosol
Similarity search - Function
GAIN domain, N-terminal / AGRL2-4 GAIN subdomain A / GPCR proteolysis site, GPS, motif / GAIN domain superfamily / : / GPS motif / G-protein-coupled receptor proteolytic site domain / GAIN-B domain profile. / : / Calcium-binding EGF domain ...GAIN domain, N-terminal / AGRL2-4 GAIN subdomain A / GPCR proteolysis site, GPS, motif / GAIN domain superfamily / : / GPS motif / G-protein-coupled receptor proteolytic site domain / GAIN-B domain profile. / : / Calcium-binding EGF domain / G-protein coupled receptors family 2 signature 2. / GPCR, family 2, secretin-like, conserved site / GPCR, family 2, secretin-like / 7 transmembrane receptor (Secretin family) / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / G-protein alpha subunit, group S / EGF-type aspartate/asparagine hydroxylation site / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / Epidermal growth factor-like domain. / Green fluorescent protein, GFP / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / EGF-like domain profile. / EGF-like domain signature 2. / EGF-like domain / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / EF-hand calcium-binding domain. / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Green fluorescent protein / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / GNAS complex locus / Adhesion G protein-coupled receptor L4
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.14 Å
AuthorsChen Q / Favara DM
Funding support United Kingdom, 1 items
OrganizationGrant numberCountry
Cancer Research UKRCCPOB-May22 - 100008 United Kingdom
CitationJournal: Nat Commun / Year: 2025
Title: Structure of the G-coupled adhesion receptor ADGRL4.
Authors: Qingchao Chen / Anastasiia Gusach / Aurora Diamante / Jayesh C Patel / Patricia C Edwards / Christopher G Tate / David M Favara /
Abstract: Adhesion G protein-coupled receptors (aGPCRs) are a 32-member family of Class B GPCRs that have diverse cellular roles including mechanosensation, cell-fate determination, neurodevelopment, immune ...Adhesion G protein-coupled receptors (aGPCRs) are a 32-member family of Class B GPCRs that have diverse cellular roles including mechanosensation, cell-fate determination, neurodevelopment, immune function and tumour biology. ADGRL4 is upregulated in the tumour microenvironment and is implicated in tumour pathogenesis across a broad range of malignancies. Inhibiting ADGRL4 is a potential therapeutic treatment for currently intractable cancers such as glioblastoma. Previous work suggested that ADGRL4 does not signal through G protein coupled pathways. However, using a sensitive bioluminescent assay, we demonstrate here that ADGRL4 couples weakly to the heterotrimeric G protein G, whilst there is no robust coupling to other G proteins (G, G, G) or β-arrestin 1 or 2. We determine the cryo-EM structure of ADGRL4 coupled to a heterotrimeric G complex to a resolution of 3.1 Å. The overall fold of ADGRL4 is similar to that of other aGPCRs, but the coupling to G is distinct with fewer interactions between the receptor and G protein. The structure is consistent with ADGRL4 being activated by its tethered agonist and represents an important step towards the development of potential inhibitors for the treatment of multiple tumour types.
History
DepositionApr 15, 2025-
Header (metadata) releaseJan 14, 2026-
Map releaseJan 14, 2026-
UpdateFeb 18, 2026-
Current statusFeb 18, 2026Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_53437.png

Downloads & links

-
Map

FileDownload / File: emd_53437.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.67 Å
Density
Contour LevelBy AUTHOR: 0.023
Minimum - Maximum-0.1206532 - 0.22037323
Average (Standard dev.)0.0000021654002 (±0.0037179745)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 268.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_53437_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_53437_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : ADGRL4 complex

EntireName: ADGRL4 complex
Components
  • Complex: ADGRL4 complex
    • Complex: Adhesion G protein-coupled receptor L4
      • Protein or peptide: Green fluorescent protein,Adhesion G protein-coupled receptor L4
    • Complex: mini-Gq
      • Protein or peptide: GNAS complex locus,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
    • Complex: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
    • Complex: G-subunit gamma-2
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

-
Supramolecule #1: ADGRL4 complex

SupramoleculeName: ADGRL4 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.9 KDa

-
Supramolecule #2: Adhesion G protein-coupled receptor L4

SupramoleculeName: Adhesion G protein-coupled receptor L4 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #3: mini-Gq

SupramoleculeName: mini-Gq / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

SupramoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #5: G-subunit gamma-2

SupramoleculeName: G-subunit gamma-2 / type: complex / ID: 5 / Parent: 1 / Macromolecule list: #4
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Green fluorescent protein,Adhesion G protein-coupled receptor L4

MacromoleculeName: Green fluorescent protein,Adhesion G protein-coupled receptor L4
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 70.00825 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MKRLPLLVVF STLLNCSYTQ YPYDVPDYAG SGGSAWSHPQ FEKGGGSGGG SGGSAWSHPQ FEKGSGHHHH HHHHHHGSGL EVLFQGPGS GVSKGEELFT GVVPILVELD GDVNGHKFSV SGEGEGDATY GKLTLKFICT TGKLPVPWPT LVTTLTYGVQ C FSRYPDHM ...String:
MKRLPLLVVF STLLNCSYTQ YPYDVPDYAG SGGSAWSHPQ FEKGGGSGGG SGGSAWSHPQ FEKGSGHHHH HHHHHHGSGL EVLFQGPGS GVSKGEELFT GVVPILVELD GDVNGHKFSV SGEGEGDATY GKLTLKFICT TGKLPVPWPT LVTTLTYGVQ C FSRYPDHM KQHDFFKSAM PEGYVQERTI FFKDDGNYKT RAEVKFEGDT LVNRIELKGI DFKEDGNILG HKLEYNYNSH NV YIMADKQ KNGIKVNFKI RHNIEDGSVQ LADHYQQNTP IGDGPVLLPD NHYLSTQSKL SKDPNEKRDH MVLLEFVTAA GIT LGMDEL YKGSGENLYF QSGSGGSGTH FAILMSSGPS IGIKDYNILT RITQLGIIIS LICLAICIFT FWFFSEIQST RTTI HKNLC CSLFLAELVF LVGINTNTNK LFCSIIAGLL HYFFLAAFAW MCIEGIHLYL IVVGVIYNKG FLHKNFYIFG YLSPA VVVG FSAALGYRYY GTTKVCWLST ENNFIWSFIG PACLIILVNL LAFGVIIYKV FRHTAGLKPE VSCFENIRSC ARGALA LLF LLGTTWIFGV LHVVHASVVT AYLFTVSNAF QGMFIFLFLC VLSRKIQEEY YRLFKNVPCC FGCLR

UniProtKB: Green fluorescent protein, Adhesion G protein-coupled receptor L4

-
Macromolecule #2: GNAS complex locus,Guanine nucleotide-binding protein G(s) subuni...

MacromoleculeName: GNAS complex locus,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
EC number: Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 30.585227 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GGSGSGDYKD DDDKGGSGSG NSKTEDQRNE EKAQREANKK IEKQLQKDKQ VYRATHRLLL LGADNSGKST IVKQMRILHG GSGGSGGTS GIFETKFQVD KVNFHMFDVG GQRDERRKWI QCFNDVTAII FVVDSSDYNR LQEALNLFKS IWNNRWLRTI S VILFLNKQ ...String:
GGSGSGDYKD DDDKGGSGSG NSKTEDQRNE EKAQREANKK IEKQLQKDKQ VYRATHRLLL LGADNSGKST IVKQMRILHG GSGGSGGTS GIFETKFQVD KVNFHMFDVG GQRDERRKWI QCFNDVTAII FVVDSSDYNR LQEALNLFKS IWNNRWLRTI S VILFLNKQ DLLAEKVLAG KSKIEDYFPE FARYTTPEDA TPEPGEDPRV TRAKYFIRDE FLRISTASGD GRHYCYPHFT CA VDTENAR RIFNDCKDII LQMNLREYNL V

UniProtKB: GNAS complex locus, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

-
Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 38.522098 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString: MHHHHHHHHS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLVS ASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG HTGYLSCCRF L DDNQIVTS ...String:
MHHHHHHHHS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLVS ASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG HTGYLSCCRF L DDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TFTGHESDIN AI CFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKADRAGVLA GHD NRVSCL GVTDDGMAVA TGSWDSFLKI WN

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

-
Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.861143 KDa
Recombinant expressionOrganism: Trichoplusia ni (cabbage looper)
SequenceString:
MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L

UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration1.1 mg/mL
BufferpH: 7.4
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionSoftware - Name: cryoSPARC / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER / Details: Ab-initio generated by cryoSPARC
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.14 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 339728
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
Final 3D classificationNumber classes: 6 / Software - Name: cryoSPARC

+
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