+Open data
-Basic information
Entry | Database: PDB / ID: 7epc | |||||||||||||||
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Title | Cryo-EM structure of inactive mGlu7 homodimer | |||||||||||||||
Components | Isoform 3 of Metabotropic glutamate receptor 7 | |||||||||||||||
Keywords | MEMBRANE PROTEIN / Cryo-EM structure / GPCR | |||||||||||||||
Function / homology | Function and homology information group III metabotropic glutamate receptor activity / adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway / adenylate cyclase inhibitor activity / negative regulation of glutamate secretion / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / serine binding / plasma membrane => GO:0005886 / G protein-coupled glutamate receptor signaling pathway / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate receptor activity ...group III metabotropic glutamate receptor activity / adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway / adenylate cyclase inhibitor activity / negative regulation of glutamate secretion / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / serine binding / plasma membrane => GO:0005886 / G protein-coupled glutamate receptor signaling pathway / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate receptor activity / glutamate binding / presynaptic active zone / asymmetric synapse / regulation of synaptic transmission, glutamatergic / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / dendritic shaft / PDZ domain binding / membrane => GO:0016020 / sensory perception of sound / cell cortex / G alpha (i) signalling events / chemical synaptic transmission / postsynaptic membrane / receptor complex / G protein-coupled receptor signaling pathway / axon / dendrite / calcium ion binding / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||||||||
Authors | Du, J. / Wang, D. / Fan, H. / Tai, L. / Lin, S. / Han, S. / Sun, F. / Wu, B. / Zhao, Q. | |||||||||||||||
Funding support | China, 4items
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Citation | Journal: Nature / Year: 2021 Title: Structures of human mGlu2 and mGlu7 homo- and heterodimers. Authors: Juan Du / Dejian Wang / Hongcheng Fan / Chanjuan Xu / Linhua Tai / Shuling Lin / Shuo Han / Qiuxiang Tan / Xinwei Wang / Tuo Xu / Hui Zhang / Xiaojing Chu / Cuiying Yi / Peng Liu / Xiaomei ...Authors: Juan Du / Dejian Wang / Hongcheng Fan / Chanjuan Xu / Linhua Tai / Shuling Lin / Shuo Han / Qiuxiang Tan / Xinwei Wang / Tuo Xu / Hui Zhang / Xiaojing Chu / Cuiying Yi / Peng Liu / Xiaomei Wang / Yu Zhou / Jean-Philippe Pin / Philippe Rondard / Hong Liu / Jianfeng Liu / Fei Sun / Beili Wu / Qiang Zhao / Abstract: The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system. These receptors probably exist as both ...The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system. These receptors probably exist as both homo- and heterodimers that have unique pharmacological and functional properties. Here we report four cryo-electron microscopy structures of the human mGlu subtypes mGlu2 and mGlu7, including inactive mGlu2 and mGlu7 homodimers; mGlu2 homodimer bound to an agonist and a positive allosteric modulator; and inactive mGlu2-mGlu7 heterodimer. We observed a subtype-dependent dimerization mode for these mGlus, as a unique dimer interface that is mediated by helix IV (and that is important for limiting receptor activity) exists only in the inactive mGlu2 structure. The structures provide molecular details of the inter- and intra-subunit conformational changes that are required for receptor activation, which distinguish class C G-protein-coupled receptors from those in classes A and B. Furthermore, our structure and functional studies of the mGlu2-mGlu7 heterodimer suggest that the mGlu7 subunit has a dominant role in controlling dimeric association and G-protein activation in the heterodimer. These insights into mGlu homo- and heterodimers highlight the complex landscape of mGlu dimerization and activation. | |||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7epc.cif.gz | 318.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7epc.ent.gz | 249.8 KB | Display | PDB format |
PDBx/mmJSON format | 7epc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7epc_validation.pdf.gz | 765.9 KB | Display | wwPDB validaton report |
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Full document | 7epc_full_validation.pdf.gz | 773.5 KB | Display | |
Data in XML | 7epc_validation.xml.gz | 44.1 KB | Display | |
Data in CIF | 7epc_validation.cif.gz | 66.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ep/7epc ftp://data.pdbj.org/pub/pdb/validation_reports/ep/7epc | HTTPS FTP |
-Related structure data
Related structure data | 31237MC 7epaC 7epbC 7epdC 7epeC 7epfC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 96276.977 Da / Num. of mol.: 2 / Mutation: N678Y, G722I, I775F, P789Y Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GRM7, GPRC1G, MGLUR7 Production host: mammal environmental sample (environmental samples) References: UniProt: Q14831-3 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Inactive mGlu7 homodimer / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: mammal environmental sample (environmental samples) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1.47 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
CTF correction | Type: NONE | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1011214 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 76.95 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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