+
Open data
-
Basic information
| Entry | ![]() | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Title | Cryo-EM structure of Gi1-bound mGlu2-mGlu4 heterodimer | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | Complex structure / Gi1-bound mGlu2-mGlu4 heterodimer / membrane protein | |||||||||
| Function / homology | Function and homology informationadenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway / regulation of response to drug / group II metabotropic glutamate receptor activity / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / intracellular glutamate homeostasis / behavioral response to nicotine / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / glutamate secretion / Class C/3 (Metabotropic glutamate/pheromone receptors) ...adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway / regulation of response to drug / group II metabotropic glutamate receptor activity / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / intracellular glutamate homeostasis / behavioral response to nicotine / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / glutamate secretion / Class C/3 (Metabotropic glutamate/pheromone receptors) / neurotransmitter secretion / glutamate receptor activity / long-term synaptic depression / regulation of glutamate secretion / astrocyte projection / cellular response to stress / regulation of dopamine secretion / regulation of synaptic transmission, glutamatergic / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / presynaptic modulation of chemical synaptic transmission / regulation of neuron apoptotic process / regulation of mitotic spindle organization / chemokine-mediated signaling pathway / response to cocaine / calcium channel regulator activity / Regulation of insulin secretion / neuropeptide signaling pathway / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / adenylate cyclase-inhibiting 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 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / GDP binding / 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 / ADORA2B mediated anti-inflammatory cytokines production / 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 / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G-protein beta-subunit binding / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / sensory perception of taste / adenylate cyclase-activating G protein-coupled receptor signaling pathway / sperm principal piece / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / presynapse / retina development in camera-type eye / GTPase binding / G protein activity / fibroblast proliferation / presynaptic membrane / Ca2+ pathway / cytoplasmic vesicle / scaffold protein binding / midbody / 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 Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
Authors | Wang X / Wang M / Xu T / Feng Y / Han S / Zhao Q / Wu B | |||||||||
| Funding support | China, 2 items
| |||||||||
Citation | Journal: Cell Res / Year: 2023Title: Structural insights into dimerization and activation of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers. Authors: Xinwei Wang / Mu Wang / Tuo Xu / Ye Feng / Qiang Shao / Shuo Han / Xiaojing Chu / Yechun Xu / Shuling Lin / Qiang Zhao / Beili Wu / ![]() Abstract: Heterodimerization of the metabotropic glutamate receptors (mGlus) has shown importance in the functional modulation of the receptors and offers potential drug targets for treating central nervous ...Heterodimerization of the metabotropic glutamate receptors (mGlus) has shown importance in the functional modulation of the receptors and offers potential drug targets for treating central nervous system diseases. However, due to a lack of molecular details of the mGlu heterodimers, understanding of the mechanisms underlying mGlu heterodimerization and activation is limited. Here we report twelve cryo-electron microscopy (cryo-EM) structures of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers in different conformational states, including inactive, intermediate inactive, intermediate active and fully active conformations. These structures provide a full picture of conformational rearrangement of mGlu2-mGlu3 upon activation. The Venus flytrap domains undergo a sequential conformational change, while the transmembrane domains exhibit a substantial rearrangement from an inactive, symmetric dimer with diverse dimerization patterns to an active, asymmetric dimer in a conserved dimerization mode. Combined with functional data, these structures reveal that stability of the inactive conformations of the subunits and the subunit-G protein interaction pattern are determinants of asymmetric signal transduction of the heterodimers. Furthermore, a novel binding site for two mGlu4 positive allosteric modulators was observed in the asymmetric dimer interfaces of the mGlu2-mGlu4 heterodimer and mGlu4 homodimer, and may serve as a drug recognition site. These findings greatly extend our knowledge about signal transduction of the mGlus. | |||||||||
| History |
|
-
Structure visualization
| Supplemental images |
|---|
-
Downloads & links
-EMDB archive
| Map data | emd_36176.map.gz | 164.2 MB | EMDB map data format | |
|---|---|---|---|---|
| Header (meta data) | emd-36176-v30.xml emd-36176.xml | 20.5 KB 20.5 KB | Display Display | EMDB header |
| Images | emd_36176.png | 42.8 KB | ||
| Filedesc metadata | emd-36176.cif.gz | 7.8 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36176 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36176 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8jd5MC ![]() 8jcuC ![]() 8jcvC ![]() 8jcwC ![]() 8jcxC ![]() 8jcyC ![]() 8jczC ![]() 8jd0C ![]() 8jd1C ![]() 8jd2C ![]() 8jd3C ![]() 8jd4C ![]() 8jd6C C: citing same article ( M: atomic model generated by this map |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
|---|---|
| Related items in Molecule of the Month |
-
Map
| File | Download / File: emd_36176.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.071 Å | ||||||||||||||||||||||||||||||||||||
| Density |
| ||||||||||||||||||||||||||||||||||||
| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
|
-Supplemental data
-
Sample components
+Entire : Gi1-bound mGlu2-mGlu4 heterodimer
+Supramolecule #1: Gi1-bound mGlu2-mGlu4 heterodimer
+Macromolecule #1: Metabotropic glutamate receptor 2
+Macromolecule #2: Metabotropic glutamate receptor 4
+Macromolecule #3: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #6: scFv
+Macromolecule #7: 1-butyl-3-chloranyl-4-(4-phenylpiperidin-1-yl)pyridin-2-one
+Macromolecule #8: GLUTAMIC ACID
+Macromolecule #9: CHOLESTEROL
+Macromolecule #10: DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE
+Macromolecule #11: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #12: 5-methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)-1,3-thiaz...
-Experimental details
-Structure determination
| Method | cryo EM |
|---|---|
Processing | single particle reconstruction |
| Aggregation state | particle |
-
Sample preparation
| Buffer | pH: 7.5 |
|---|---|
| Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
| Microscope | FEI TITAN KRIOS |
|---|---|
| Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 70.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.8 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
-
Image processing
| Startup model | Type of model: INSILICO MODEL |
|---|---|
| Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 939819 |
| Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
| Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Movie
Controller
About Yorodumi




Keywords
Homo sapiens (human)
Authors
China, 2 items
Citation

























































Z (Sec.)
Y (Row.)
X (Col.)





















Baculovirus expression vector pFastBac1-HM





FIELD EMISSION GUN
