+Open data
-Basic information
Entry | Database: PDB / ID: 6n52 | |||||||||
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Title | Metabotropic Glutamate Receptor 5 Apo Form | |||||||||
Components | Metabotropic glutamate receptor 5 | |||||||||
Keywords | MEMBRANE PROTEIN / Cell Surface Receptor | |||||||||
Function / homology | Function and homology information A2A adenosine receptor binding / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / positive regulation of long-term neuronal synaptic plasticity / desensitization of G protein-coupled receptor signaling pathway / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / G protein-coupled glutamate receptor signaling pathway / astrocyte projection ...A2A adenosine receptor binding / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / positive regulation of long-term neuronal synaptic plasticity / desensitization of G protein-coupled receptor signaling pathway / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / Class C/3 (Metabotropic glutamate/pheromone receptors) / : / glutamate receptor activity / Neurexins and neuroligins / protein tyrosine kinase activator activity / : / regulation of synaptic transmission, glutamatergic / protein tyrosine kinase binding / dendritic shaft / learning / locomotory behavior / G protein-coupled receptor activity / postsynaptic density membrane / synapse organization / Schaffer collateral - CA1 synapse / cognition / cellular response to amyloid-beta / G alpha (q) signalling events / chemical synaptic transmission / positive regulation of MAPK cascade / dendritic spine / learning or memory / glutamatergic synapse / dendrite / regulation of DNA-templated transcription / identical protein binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||
Authors | Koehl, A. / Hu, H. / Feng, D. / Sun, B. / Weis, W.I. / Skiniotis, G.S. / Mathiesen, J.M. / Kobilka, B.K. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nature / Year: 2019 Title: Structural insights into the activation of metabotropic glutamate receptors. Authors: Antoine Koehl / Hongli Hu / Dan Feng / Bingfa Sun / Yan Zhang / Michael J Robertson / Matthew Chu / Tong Sun Kobilka / Toon Laeremans / Jan Steyaert / Jeffrey Tarrasch / Somnath Dutta / ...Authors: Antoine Koehl / Hongli Hu / Dan Feng / Bingfa Sun / Yan Zhang / Michael J Robertson / Matthew Chu / Tong Sun Kobilka / Toon Laeremans / Jan Steyaert / Jeffrey Tarrasch / Somnath Dutta / Rasmus Fonseca / William I Weis / Jesper M Mathiesen / Georgios Skiniotis / Brian K Kobilka / Abstract: Metabotropic glutamate receptors are family C G-protein-coupled receptors. They form obligate dimers and possess extracellular ligand-binding Venus flytrap domains, which are linked by cysteine-rich ...Metabotropic glutamate receptors are family C G-protein-coupled receptors. They form obligate dimers and possess extracellular ligand-binding Venus flytrap domains, which are linked by cysteine-rich domains to their 7-transmembrane domains. Spectroscopic studies show that signalling is a dynamic process, in which large-scale conformational changes underlie the transmission of signals from the extracellular Venus flytraps to the G protein-coupling domains-the 7-transmembrane domains-in the membrane. Here, using a combination of X-ray crystallography, cryo-electron microscopy and signalling studies, we present a structural framework for the activation mechanism of metabotropic glutamate receptor subtype 5. Our results show that agonist binding at the Venus flytraps leads to a compaction of the intersubunit dimer interface, thereby bringing the cysteine-rich domains into close proximity. Interactions between the cysteine-rich domains and the second extracellular loops of the receptor enable the rigid-body repositioning of the 7-transmembrane domains, which come into contact with each other to initiate signalling. | |||||||||
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 | 6n52.cif.gz | 266.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6n52.ent.gz | 208.4 KB | Display | PDB format |
PDBx/mmJSON format | 6n52.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6n52_validation.pdf.gz | 817.9 KB | Display | wwPDB validaton report |
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Full document | 6n52_full_validation.pdf.gz | 824.3 KB | Display | |
Data in XML | 6n52_validation.xml.gz | 42.8 KB | Display | |
Data in CIF | 6n52_validation.cif.gz | 65.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/n5/6n52 ftp://data.pdbj.org/pub/pdb/validation_reports/n5/6n52 | HTTPS FTP |
-Related structure data
Related structure data | 0346MC 0345C 0347C 6n4xC 6n4yC 6n50C 6n51C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 97677.945 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GRM5, GPRC1E, MGLUR5 / Plasmid: PVL1392 / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P41594 #2: Sugar | ChemComp-NAG / |
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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: Metabotropic Glutamate Receptor 5 in Nanodiscs / Type: COMPLEX / Details: Metabotropic Glutamate Receptor 5 in Nanodiscs / Entity ID: #1 / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Value: 0.2 MDa / Experimental value: NO | |||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) / Strain: Sf9 | |||||||||||||||
Buffer solution | pH: 7.5 Details: 100mM NaCl, 20 mM HEPES pH 7.5, 5uM FFMTEB added as a negative allosteric modulator. | |||||||||||||||
Buffer component |
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Specimen | Conc.: 7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: This sample was mono disperse as assayed by gel filtration. | |||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293 K Details: Addition 0.0005% Amphipol A8-35was added to sample prior to apply to grid; 3.5ul sample was applied; blot for 1s before plunging |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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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 magnification: 130000 X / Calibrated magnification: 47169 X / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
Image recording | Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 123096 / Symmetry type: POINT |