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- PDB-9wqk: GRM5-Gi Complex Structure -

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Basic information

Entry
Database: PDB / ID: 9wqk
TitleGRM5-Gi Complex Structure
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Metabotropic glutamate receptor 5
  • scFv16
KeywordsMEMBRANE PROTEIN / Receptor complex
Function / homology
Function and homology information


A2A adenosine receptor binding / sensory perception of hot stimulus / negative regulation of dendritic spine morphogenesis / : / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / positive regulation of cellular response to hypoxia / protein localization to nuclear inner membrane / operant conditioning / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway ...A2A adenosine receptor binding / sensory perception of hot stimulus / negative regulation of dendritic spine morphogenesis / : / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / positive regulation of cellular response to hypoxia / protein localization to nuclear inner membrane / operant conditioning / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / positive regulation of long-term neuronal synaptic plasticity / positive regulation of sensory perception of pain / negative regulation of excitatory postsynaptic potential / positive regulation of dopamine secretion / desensitization of G protein-coupled receptor signaling pathway / G protein-coupled glutamate receptor signaling pathway / positive regulation of neural precursor cell proliferation / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate receptor activity / nuclear inner membrane / Neurexins and neuroligins / astrocyte projection / response to morphine / response to corticosterone / temperature homeostasis / protein tyrosine kinase activator activity / conditioned place preference / regulation of synaptic transmission, glutamatergic / positive regulation of calcium-mediated signaling / regulation of eating behavior / regulation of long-term synaptic depression / 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 / response to amphetamine / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / protein tyrosine kinase binding / cellular response to forskolin / locomotory behavior / regulation of mitotic spindle organization / dendritic shaft / mast cell degranulation / chemokine-mediated signaling pathway / neuropeptide signaling pathway / Regulation of insulin secretion / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / synapse organization / postsynaptic density membrane / G protein-coupled receptor binding / cognition / response to peptide hormone / Schaffer collateral - CA1 synapse / cellular response to amyloid-beta / G protein-coupled receptor activity / 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 / G beta:gamma signalling through BTK / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / 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 / Inactivation, recovery and regulation of the phototransduction cascade / G alpha (12/13) signalling events / G-protein beta-subunit binding / extracellular vesicle / positive regulation of cytosolic calcium ion concentration / Thrombin signalling through proteinase activated receptors (PARs)
Similarity search - Function
GPCR, family 3, metabotropic glutamate receptor 5 / Metabotropic glutamate receptor, Homer-binding domain / Homer-binding domain of metabotropic glutamate receptor / GluR_Homer-bdg / GPCR, family 3, metabotropic glutamate receptor / : / G-protein coupled receptors family 3 signature 1. / G-protein coupled receptors family 3 signature 3. / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain ...GPCR, family 3, metabotropic glutamate receptor 5 / Metabotropic glutamate receptor, Homer-binding domain / Homer-binding domain of metabotropic glutamate receptor / GluR_Homer-bdg / GPCR, family 3, metabotropic glutamate receptor / : / G-protein coupled receptors family 3 signature 1. / G-protein coupled receptors family 3 signature 3. / G-protein coupled receptors family 3 signature 2. / GPCR, family 3, nine cysteines domain / GPCR, family 3, nine cysteines domain superfamily / Nine Cysteines Domain of family 3 GPCR / GPCR, family 3, conserved site / GPCR, family 3 / G-protein coupled receptors family 3 profile. / GPCR family 3, C-terminal / 7 transmembrane sweet-taste receptor of 3 GCPR / G-protein alpha subunit, group I / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like 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 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
CHOLESTEROL / GAMMA-L-GLUTAMIC ACID / 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide / Metabotropic glutamate receptor 5 / 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
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å
AuthorsLu, Y. / Wen, T.L. / Shen, Y.Q. / Yang, X.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Sci Adv / Year: 2026
Title: G protein selectivity in group I metabotropic glutamate receptors.
Authors: Yue Lu / Tianlei Wen / Xuhang Lu / Guimin Zhang / Tingting Meng / Tianjin Liu / Xinyan Wang / Yuequan Shen / Xue Yang /
Abstract: Metabotropic glutamate (mGlu) receptors are class C G protein-coupled receptor involved in synaptic transmission and neurological disorders. Group I mGlu receptors (mGlu1 and mGlu5) predominantly ...Metabotropic glutamate (mGlu) receptors are class C G protein-coupled receptor involved in synaptic transmission and neurological disorders. Group I mGlu receptors (mGlu1 and mGlu5) predominantly couple to G, whereas group II and III receptors primarily engage G. Although G-coupling mechanisms have been defined for several group II/III receptors, how group I receptors preferentially engage G remains unclear. Here we report cryo-electron microscopy structures of active mGlu-G protein complexes (mGlu1-G, mGlu1-G, mGlu5-G, and mGlu5-G) bound to l-glutamate and positive allosteric modulators (PAMs), together with two additional activated-state structures of mGlu1. Comparative structural and biochemical analyses identify a group I-specific ICL2 insertion that promotes preferential G engagement. Each receptor dimer asymmetrically binds one G protein heterotrimer via an intracellular pocket engaging the Gα amino-terminal helix. PAM binding to one 7TM domain induces W rotation and TM6 outward movement, bringing the two 7TMs into closer. These findings provide a structural basis for preferential G engagement and activation of group I mGlu receptors.
History
DepositionSep 11, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0May 27, 2026Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0May 27, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0May 27, 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
X: Metabotropic glutamate receptor 5
Y: Metabotropic glutamate receptor 5
A: Guanine nucleotide-binding protein G(i) subunit alpha-1
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
F: scFv16
hetero molecules


Theoretical massNumber of molelcules
Total (without water)310,27127
Polymers304,6796
Non-polymers5,59221
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

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Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG

#2: Protein Guanine nucleotide-binding protein G(i) subunit alpha-1 / Adenylate cyclase-inhibiting G alpha protein


Mass: 40414.047 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P63096, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
#3: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37416.930 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873
#4: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 8506.765 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

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Protein / Antibody / Sugars , 3 types, 11 molecules XYF

#1: Protein Metabotropic glutamate receptor 5 / mGluR5


Mass: 95310.016 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GRM5, GPRC1E, MGLUR5 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P41594
#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: Homo sapiens (human)
#8: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Non-polymers , 4 types, 13 molecules

#6: Chemical ChemComp-YKU / 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide


Mass: 364.399 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H16N4O / Comment: antipsychotic*YM
#7: Chemical ChemComp-GGL / GAMMA-L-GLUTAMIC ACID / L-GLUTAMIC ACID


Type: L-gamma-peptide, C-delta linking / Mass: 147.129 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C5H9NO4
#9: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cl
#10: Chemical
ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C27H46O

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Details

Has ligand of interestN
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

ComponentName: GRM5-Gi complex / Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT
Molecular weightValue: 0.3 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.2
SpecimenConc.: 10 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE / Humidity: 100 %

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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: 19000 nm / Nominal defocus min: 6000 nm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

EM software
IDNameVersionCategory
1RELION5particle selection
2PHENIX1.19_4092model refinement
3EPUimage acquisition
5CTFFIND4CTF correction
13RELION53D reconstruction
CTF correctionType: NONE
3D reconstructionResolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 161016 / Symmetry type: POINT
RefinementHighest resolution: 3.7 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00519711
ELECTRON MICROSCOPYf_angle_d0.57526745
ELECTRON MICROSCOPYf_dihedral_angle_d13.1767122
ELECTRON MICROSCOPYf_chiral_restr0.0443037
ELECTRON MICROSCOPYf_plane_restr0.0033347

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