+Open data
-Basic information
Entry | Database: PDB / ID: 7mts | ||||||
---|---|---|---|---|---|---|---|
Title | CryoEM Structure of mGlu2 - Gi Complex | ||||||
Components |
| ||||||
Keywords | MEMBRANE PROTEIN/SIGNALING PROTEIN / Metabotropic Glutamate Receptor 2 (mGlu2) (mGluR2) / Family C G protein-coupled receptor (GPCR) / Heterotrimeric G protein / CryoEM structure / MEMBRANE PROTEIN / MEMBRANE PROTEIN-SIGNALING PROTEIN complex | ||||||
Function / homology | Function and homology information regulation of response to drug / group II metabotropic glutamate receptor activity / behavioral response to nicotine / intracellular glutamate homeostasis / astrocyte projection / G protein-coupled glutamate receptor signaling pathway / negative regulation of adenylate cyclase activity / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate secretion / glutamate receptor activity ...regulation of response to drug / group II metabotropic glutamate receptor activity / behavioral response to nicotine / intracellular glutamate homeostasis / astrocyte projection / G protein-coupled glutamate receptor signaling pathway / negative regulation of adenylate cyclase activity / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate secretion / glutamate receptor activity / regulation of glutamate secretion / long-term synaptic depression / regulation of dopamine secretion / calcium channel regulator activity / T cell migration / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / regulation of synaptic transmission, glutamatergic / presynaptic modulation of chemical synaptic transmission / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / response to cocaine / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / response to peptide hormone / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GDP binding / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / gene expression / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / scaffold protein binding / G alpha (q) signalling events / chemical synaptic transmission / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / G protein-coupled receptor signaling pathway / lysosomal membrane / cell division / axon / GTPase activity / centrosome / glutamatergic synapse / dendrite / synapse / GTP binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
Authors | Seven, A.B. / Barros-Alvarez, X. / Skiniotis, G. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Nature / Year: 2021 Title: G-protein activation by a metabotropic glutamate receptor. Authors: Alpay B Seven / Ximena Barros-Álvarez / Marine de Lapeyrière / Makaía M Papasergi-Scott / Michael J Robertson / Chensong Zhang / Robert M Nwokonko / Yang Gao / Justin G Meyerowitz / Jean- ...Authors: Alpay B Seven / Ximena Barros-Álvarez / Marine de Lapeyrière / Makaía M Papasergi-Scott / Michael J Robertson / Chensong Zhang / Robert M Nwokonko / Yang Gao / Justin G Meyerowitz / Jean-Philippe Rocher / Dominik Schelshorn / Brian K Kobilka / Jesper M Mathiesen / Georgios Skiniotis / Abstract: Family C G-protein-coupled receptors (GPCRs) operate as obligate dimers with extracellular domains that recognize small ligands, leading to G-protein activation on the transmembrane (TM) domains of ...Family C G-protein-coupled receptors (GPCRs) operate as obligate dimers with extracellular domains that recognize small ligands, leading to G-protein activation on the transmembrane (TM) domains of these receptors by an unknown mechanism. Here we show structures of homodimers of the family C metabotropic glutamate receptor 2 (mGlu2) in distinct functional states and in complex with heterotrimeric G. Upon activation of the extracellular domain, the two transmembrane domains undergo extensive rearrangement in relative orientation to establish an asymmetric TM6-TM6 interface that promotes conformational changes in the cytoplasmic domain of one protomer. Nucleotide-bound G can be observed pre-coupled to inactive mGlu2, but its transition to the nucleotide-free form seems to depend on establishing the active-state TM6-TM6 interface. In contrast to family A and B GPCRs, G-protein coupling does not involve the cytoplasmic opening of TM6 but is facilitated through the coordination of intracellular loops 2 and 3, as well as a critical contribution from the C terminus of the receptor. The findings highlight the synergy of global and local conformational transitions to facilitate a new mode of G-protein activation. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7mts.cif.gz | 410.4 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7mts.ent.gz | 331 KB | Display | PDB format |
PDBx/mmJSON format | 7mts.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7mts_validation.pdf.gz | 766.6 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7mts_full_validation.pdf.gz | 780 KB | Display | |
Data in XML | 7mts_validation.xml.gz | 58.7 KB | Display | |
Data in CIF | 7mts_validation.cif.gz | 89.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mt/7mts ftp://data.pdbj.org/pub/pdb/validation_reports/mt/7mts | HTTPS FTP |
-Related structure data
Related structure data | 23996MC 7mtqC 7mtrC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data | |
EM raw data | EMPIAR-10979 (Title: CryoEM Structure of mGlu2 - Gi Complex / Data size: 21.6 TB Data #1: Unaligned multi-frame micrographs of mGlu2 - Gi Complex [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules CDE
#2: Protein | Mass: 40415.031 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 |
---|---|
#3: Protein | Mass: 37342.785 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 | Mass: 7861.143 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 |
-Protein / Sugars , 2 types, 4 molecules AB
#1: Protein | Mass: 93932.445 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GRM2, GPRC1B, MGLUR2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q14416 #7: Sugar | |
---|
-Non-polymers , 2 types, 3 molecules
#5: Chemical | ChemComp-ZQY / |
---|---|
#6: Chemical |
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: mGlu2 - Heterotrimeric Gi complex / Type: COMPLEX Details: Heterotrimeric G protein coupled metabotropic glutamate receptor 2 bound to Ago-PAM ADX55164 and L-Glutamate Entity ID: #1-#4 / Source: RECOMBINANT |
---|---|
Molecular weight | Value: 0.277 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid type: Quantifoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Image recording | Electron dose: 1.3 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 799323 / Details: A composite map of four locally refined maps. / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|