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- PDB-9x74: Human GPR30 -Gq complex -

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Basic information

Entry
Database: PDB / ID: 9x74
TitleHuman GPR30 -Gq complex
Components
  • G-protein coupled estrogen receptor 1
  • 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-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
  • scFv16
KeywordsMEMBRANE PROTEIN / Receptor / GPCR / Complex
Function / homology
Function and homology information


negative regulation of leukocyte activation / nuclear fragmentation involved in apoptotic nuclear change / G protein-coupled estrogen receptor activity / positive regulation of cardiac vascular smooth muscle cell differentiation / negative regulation of cell cycle process / keratin filament / positive regulation of inositol trisphosphate biosynthetic process / apoptotic chromosome condensation / positive regulation of uterine smooth muscle contraction / negative regulation of lipid biosynthetic process ...negative regulation of leukocyte activation / nuclear fragmentation involved in apoptotic nuclear change / G protein-coupled estrogen receptor activity / positive regulation of cardiac vascular smooth muscle cell differentiation / negative regulation of cell cycle process / keratin filament / positive regulation of inositol trisphosphate biosynthetic process / apoptotic chromosome condensation / positive regulation of uterine smooth muscle contraction / negative regulation of lipid biosynthetic process / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of neurotransmitter secretion / steroid hormone binding / cellular response to mineralocorticoid stimulus / sensory perception of chemical stimulus / positive regulation of G protein-coupled receptor signaling pathway / negative regulation of adenylate cyclase activity / mu-type opioid receptor binding / G protein-coupled adenosine receptor signaling pathway / corticotropin-releasing hormone receptor 1 binding / positive regulation of neural precursor cell proliferation / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / negative regulation of synaptic transmission / G alpha (z) signalling events / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of neurogenesis / G alpha (q) signalling events / dendritic spine membrane / beta-2 adrenergic receptor binding / negative regulation of fat cell differentiation / G alpha (i) signalling events / positive regulation of urine volume / Thrombin signalling through proteinase activated receptors (PARs) / steroid hormone receptor signaling pathway / cellular response to peptide hormone stimulus / presynaptic active zone / dendritic spine head / nuclear estrogen receptor activity / gamma-aminobutyric acid signaling pathway / photoreceptor outer segment membrane / spectrin binding / positive regulation of epidermal growth factor receptor signaling pathway / sensory perception of taste / alkylglycerophosphoethanolamine phosphodiesterase activity / regulation of calcium ion transport / positive regulation of release of cytochrome c from mitochondria / negative regulation of apoptotic signaling pathway / retina development in camera-type eye / negative regulation of vascular associated smooth muscle cell proliferation / neuronal action potential / nuclear receptor-mediated steroid hormone signaling pathway / positive regulation of endothelial cell apoptotic process / cardiac muscle cell apoptotic process / photoreceptor outer segment / D1 dopamine receptor binding / positive regulation of vascular associated smooth muscle cell proliferation / regulation of cytosolic calcium ion concentration / neuronal dense core vesicle / adenylate cyclase-activating adrenergic receptor signaling pathway / steroid binding / insulin-like growth factor receptor binding / positive regulation of superoxide anion generation / response to nutrient / photoreceptor inner segment / Adenylate cyclase inhibitory pathway / ionotropic glutamate receptor binding / cytoplasmic vesicle membrane / positive regulation of release of sequestered calcium ion into cytosol / axon terminus / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / adenylate cyclase activator activity / hippocampal mossy fiber to CA3 synapse / Peptide ligand-binding receptors / dendritic shaft / cellular response to estradiol stimulus / positive regulation of protein localization to plasma membrane / cellular response to tumor necrosis factor / cellular response to glucose stimulus / positive regulation of insulin secretion / trans-Golgi network / Regulation of insulin secretion / negative regulation of ERK1 and ERK2 cascade / negative regulation of inflammatory response / vasodilation
Similarity search - Function
: / G-protein alpha subunit, group S / 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 alpha subunit, group S / 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 / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / 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(s) subunit alpha isoforms short / Guanine nucleotide-binding protein G(i) subunit alpha-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G protein-coupled estrogen receptor 1
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Homo sapiens (human)
Bos taurus (domestic cattle)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.15 Å
AuthorsKaneda, S. / Oshima, H.S. / Akasaka, H. / Shihoya, W. / Nureki, O.
Funding support Japan, 1items
OrganizationGrant numberCountry
Japan Society for the Promotion of Science (JSPS)21H05037 Japan
CitationJournal: Elife / Year: 2026
Title: Cryo-EM structure of the bicarbonate receptor GPR30.
Authors: Shota Kaneda / Airi Jo-Watanabe / Hiroaki Akasaka / Hidetaka S Oshima / Takehiko Yokomizo / Wataru Shihoya / Osamu Nureki /
Abstract: G-protein-coupled receptor 30 (GPR30) is a bicarbonate receptor that plays a vital role in cellular responses to extracellular pH and ion homeostasis. Despite its significance, the mechanisms by ...G-protein-coupled receptor 30 (GPR30) is a bicarbonate receptor that plays a vital role in cellular responses to extracellular pH and ion homeostasis. Despite its significance, the mechanisms by which GPR30 interacts with bicarbonate ions remain elusive. There is no consensus on a drug that targets GPR30, and difficulties in pharmacological analyses have limited biological and drug discovery research on GPR30. Here, we present the cryo-electron microscopy structure of human GPR30 in the presence of bicarbonate ions at 3.15 Å resolution. Our structure reveals unique extracellular pockets and critical residues for bicarbonate binding and activation. Functional assays demonstrate that mutations in these residues impair bicarbonate-induced GPR30 activation, underscoring their importance in receptor function. This study also provides insights into G-protein coupling, highlighting the structural divergence between GPR30 and other G-protein-coupled receptors (GPCRs). Our findings not only advance the understanding of the role of GPR30 in pH homeostasis but also pave the way for the development of high-affinity drugs targeting GPR30 for therapeutic interventions in diseases associated with acid-base imbalance.
History
DepositionOct 16, 2025Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 26, 2026Provider: repository / Type: Initial release
Revision 1.0Aug 26, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Aug 26, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Aug 26, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
G: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
A: Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
R: G-protein coupled estrogen receptor 1
S: scFv16


Theoretical massNumber of molelcules
Total (without water)199,1095
Polymers199,1095
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 40470.105 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gnb1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P54311
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 7563.750 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768
#3: Protein Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Adenylate cyclase-inhibiting G alpha protein / Adenylate cyclase-stimulating G alpha protein


Mass: 29027.848 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Bos taurus (domestic cattle)
Gene: GNAI2, GNAI2B, GNAS, GNAS1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P04899, UniProt: P04896, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
#4: Protein G-protein coupled estrogen receptor 1 / Chemoattractant receptor-like 2 / Flow-induced endothelial G-protein coupled receptor 1 / FEG-1 / G ...Chemoattractant receptor-like 2 / Flow-induced endothelial G-protein coupled receptor 1 / FEG-1 / G protein-coupled estrogen receptor 1 / G-protein coupled receptor 30 / GPCR-Br / IL8-related receptor DRY12 / Lymphocyte-derived G-protein coupled receptor / LYGPR / Membrane estrogen receptor / mER


Mass: 94326.938 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GPER1, CEPR, CMKRL2, DRY12, GPER, GPR30 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q99527
#5: Antibody scFv16


Mass: 27720.795 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera frugiperda (fall armyworm)
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Human GPR30 -Gq complexCOMPLEXall0RECOMBINANT
2Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1COMPLEX#11RECOMBINANT
3Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2COMPLEX#21RECOMBINANT
4Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2,Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLasCOMPLEX#31RECOMBINANT
5GPR30, LgBiT, EGFPCOMPLEX#41RECOMBINANT
6scFv16COMPLEX#51RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
22Homo sapiens (human)9606
33Rattus norvegicus (Norway rat)10116
44Homo sapiens (human)9606
54Bos taurus (domestic cattle)9913
65Homo sapiens (human)9606
76Mus musculus (house mouse)10090
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
21Spodoptera frugiperda (fall armyworm)7108
32Spodoptera frugiperda (fall armyworm)7108
43Spodoptera frugiperda (fall armyworm)7108
54Spodoptera frugiperda (fall armyworm)7108
65Spodoptera frugiperda (fall armyworm)7108
76Spodoptera frugiperda (fall armyworm)7108
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 50.66 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1cryoSPARC4particle selection
2PHENIX1.20.1_4487model refinement
13cryoSPARC43D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.15 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 522404 / Symmetry type: POINT
RefinementHighest resolution: 3.15 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0038652
ELECTRON MICROSCOPYf_angle_d0.50811758
ELECTRON MICROSCOPYf_dihedral_angle_d4.3971199
ELECTRON MICROSCOPYf_chiral_restr0.041352
ELECTRON MICROSCOPYf_plane_restr0.0041493

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