[English] 日本語
Yorodumi
- EMDB-64407: Cryo-EM structure of the ZQ16-bound GPR84 receptor-Gi complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-64407
TitleCryo-EM structure of the ZQ16-bound GPR84 receptor-Gi complex
Map dataCryo-EM structure of the ZQ-16-bound GPR84 receptor-Gi complex
Sample
  • Complex: ZQ16-bound GPR84 receptor-Gi complex
    • Protein or peptide: G-protein coupled receptor 84
    • Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-1
    • Protein or peptide: 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(O) subunit gamma-2
  • Ligand: 2-hexylsulfanyl-4-oxidanyl-1~{H}-pyrimidin-6-one
KeywordsGPCR / MCFA / complex / agonist / MEMBRANE PROTEIN
Function / homology
Function and homology information


urotensin II receptor activity / tertiary granule membrane / specific granule membrane / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding ...urotensin II receptor activity / tertiary granule membrane / specific granule membrane / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting dopamine receptor signaling pathway / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / regulation of G protein-coupled receptor signaling pathway / cellular response to forskolin / regulation of mitotic spindle organization / mast cell degranulation / chemokine-mediated signaling pathway / establishment of mitotic spindle orientation / neuropeptide signaling pathway / Regulation of insulin secretion / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / response to peptide hormone / G-protein beta/gamma-subunit complex binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / GDP binding / photoreceptor disc membrane / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / extracellular vesicle / Thrombin signalling through proteinase activated receptors (PARs) / adenylate cyclase-activating G protein-coupled receptor signaling pathway / signaling receptor complex adaptor activity / spindle pole / ciliary basal body / GTPase binding / midbody / G protein activity / Ca2+ pathway / cell cortex / 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 / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / cytoplasmic side of plasma membrane / Ras protein signal transduction / cell division / signaling receptor complex / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / centrosome / GTPase activity / Neutrophil degranulation / GTP binding / synapse / protein-containing complex binding / magnesium ion binding / signal transduction / extracellular exosome / membrane / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
G-protein alpha subunit, group I / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily ...G-protein alpha subunit, group I / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / 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 / Guanine nucleotide-binding protein, beta subunit / G protein beta WD-40 repeat protein / G-protein, beta subunit / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 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
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(i) subunit alpha-1 / G protein-coupled receptor 84
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsChoi MK / Cho HS
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Exp Mol Med / Year: 2026
Title: Pharmacological modulation of GPR84 revealed by dual states structures and immune functional assays.
Authors: Myung Kyung Choi / Dong Jin Park / Pankyung Kim / Hee Seong Choi / Sorin Myung / Youngki Yoo / Nienping Chang / Ga-Yeon Yoon / Hye Jin Kang / Sang-Jun Ha / Hyun-Soo Cho /
Abstract: G-protein-coupled receptor 84 (GPR84) is an orphan class A GPCR selectively activated by medium chain fatty acids and highly expressed in immune cells, where it modulates pro-inflammatory signaling. ...G-protein-coupled receptor 84 (GPR84) is an orphan class A GPCR selectively activated by medium chain fatty acids and highly expressed in immune cells, where it modulates pro-inflammatory signaling. The structural basis of GPR84 inactivation and antagonism has remained unclear, limiting the rational design of pathway-selective modulators despite its clinical relevance in metabolic inflammation and fibrotic diseases. Here, we report cryo-electron microscopy structures of human GPR84 in inactive and active states. The 3.5 Å inactive structure bound to the antagonist GLPG1205 reveals a lid-like conformation of extracellular loop 2 and an inward reorientation of Arg172, with the antagonist head group blocking the allosteric sodium-binding site. Molecular dynamics simulations further support these findings, identifying an aberrant TM5, TM6 lateral entry gate. By contrast, the 3.17 Å agonist ZQ-16, Gαi complex, shows a rearranged toggle switch and comparative analyses highlight extracellular loop 2 conformational plasticity. Immune functional assays in THP-1 cells demonstrated that ZQ-16 elicited GPR84-dependent activation and cytokine production, which were effectively abrogated by GLPG1205. Mutagenesis combined with functional assays validates key ligand interactions, providing a framework for the rational design of pathway selective GPR84 modulators.
History
DepositionApr 29, 2025-
Header (metadata) releaseSep 23, 2026-
Map releaseSep 23, 2026-
UpdateSep 23, 2026-
Current statusSep 23, 2026Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_64407.png

Downloads & links

-
Map

FileDownload / File: emd_64407.map.gz / Format: CCP4 / Size: 163.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryo-EM structure of the ZQ-16-bound GPR84 receptor-Gi complex
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.9 Å/pix.
x 350 pix.
= 315.455 Å		0.9 Å/pix.
x 350 pix.
= 315.455 Å		0.9 Å/pix.
x 350 pix.
= 315.455 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.9013 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.135
Minimum - Maximum-0.2811857 - 0.62734693
Average (Standard dev.)-0.00042113214 (±0.011038369)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions350350350
Spacing350350350
CellA=B=C: 315.45502 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: Half B map

Fileemd_64407_half_map_1.map
AnnotationHalf_B map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Half A map

Fileemd_64407_half_map_2.map
AnnotationHalf_A map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : ZQ16-bound GPR84 receptor-Gi complex

EntireName: ZQ16-bound GPR84 receptor-Gi complex
Components
  • Complex: ZQ16-bound GPR84 receptor-Gi complex
    • Protein or peptide: G-protein coupled receptor 84
    • Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-1
    • Protein or peptide: 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(O) subunit gamma-2
  • Ligand: 2-hexylsulfanyl-4-oxidanyl-1~{H}-pyrimidin-6-one

-
Supramolecule #1: ZQ16-bound GPR84 receptor-Gi complex

SupramoleculeName: ZQ16-bound GPR84 receptor-Gi complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 130 KDa

-
Macromolecule #1: G-protein coupled receptor 84

MacromoleculeName: G-protein coupled receptor 84 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 43.537535 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: DYKDDDDKSS DANFSCYHES VLGYRYVAVS WGVVVAVTGT VGNVLTLLAL AIQPKLRTRF NLLIANLTLA DLLYCTLLQP FSVDTYLHL HWRTGATFCR VFGLLLFASN SVSILTLCLI ALGRYLLIAH PKLFPQVFSA KGIVLALVST WVVGVASFAP L WPIYILVP ...String:
DYKDDDDKSS DANFSCYHES VLGYRYVAVS WGVVVAVTGT VGNVLTLLAL AIQPKLRTRF NLLIANLTLA DLLYCTLLQP FSVDTYLHL HWRTGATFCR VFGLLLFASN SVSILTLCLI ALGRYLLIAH PKLFPQVFSA KGIVLALVST WVVGVASFAP L WPIYILVP VVCTCSFDRI RGRPYTTILM GIYFVLGLSS VGIFYCLIHR QVKRAAQALD QYKLRQASIH SNHVARTDEA MP GRFQELD SRLASGGPSE GISSEPVSAA TTQTLEGDSS EVGDQINSKR AKQMAEKSPP EASAKAQPIK GARRAPDSSS EFG KVTRMC FAVFLCFALS YIPFLLLNIL DARVQAPRVV HMLAANLTWL NGCINPVLYA AMNRQFRQAY GSILKRGPR

UniProtKB: G protein-coupled receptor 84

-
Macromolecule #2: Guanine nucleotide-binding protein G(i) subunit alpha-1

MacromoleculeName: Guanine nucleotide-binding protein G(i) subunit alpha-1
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: 40.691316 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: EFMGCTLSAE DKAAVERSKM IDRNLREDGE KAAREVKLLL LGAGESGKST IVKQMKIIHE AGYSEEECKQ YKAVVYSNTI QSIIAIIRA MGRLKIDFGD SARADDARQL FVLAGAAEEG FMTAELAGVI KRLWKDSGVQ ACFNRSREYQ LNDSAAYYLN D LDRIAQPN ...String:
EFMGCTLSAE DKAAVERSKM IDRNLREDGE KAAREVKLLL LGAGESGKST IVKQMKIIHE AGYSEEECKQ YKAVVYSNTI QSIIAIIRA MGRLKIDFGD SARADDARQL FVLAGAAEEG FMTAELAGVI KRLWKDSGVQ ACFNRSREYQ LNDSAAYYLN D LDRIAQPN YIPTQQDVLR TRVKTTGIVE THFTFKDLHF KMFDVGGQRS ERKKWIHCFE GVTAIIFCVA LSDYDLVLAE DE EMNRMHE SMKLFDSICN NKWFTDTSII LFLNKKDLFE EKIKKSPLTI CYPEYAGSNT YEEAAAYIQC QFEDLNKRKD TKE IYTHFT CATDTKNVQF VFDAVTDVII KNNLKDCGLF

UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1

-
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: 39.475137 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR ...String:
MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TF TGHESDI NAICFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKA DRAGVL AGHDNRVSCL GVTDDGMAVA TGSWDSFLKI WNG

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: Spodoptera frugiperda (fall armyworm)
SequenceString:
MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L

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

-
Macromolecule #5: 2-hexylsulfanyl-4-oxidanyl-1~{H}-pyrimidin-6-one

MacromoleculeName: 2-hexylsulfanyl-4-oxidanyl-1~{H}-pyrimidin-6-one / type: ligand / ID: 5 / Number of copies: 1 / Formula: A1L9K
Molecular weightTheoretical: 228.311 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration3 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormulaName
20.0 mMHEPES4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
150.0 mMNaClsodium chlorid
3.0 mMMgCl2magnesium chloride
0.03 %DDMdodecyl maltoside
0.003 %CHScholesteryl hemisuccinate
1.35 uMZQ-16ZQ-16
GridModel: Quantifoil / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
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: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.1 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

Particle selectionNumber selected: 971539
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 204250
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING
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