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Yorodumi- EMDB-0345: Metabotropic Glutamate Receptor 5 bound to L-quisqualate and Nb43 -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0345 | |||||||||
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Title | Metabotropic Glutamate Receptor 5 bound to L-quisqualate and Nb43 | |||||||||
Map data | Metabotropic Glutamate Receptor 5 bound to L-quisqualate and Nb43, primary map | |||||||||
Sample |
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Function / homology | Function and homology information A2A adenosine receptor binding / regulation of translational elongation / 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 / G protein-coupled glutamate receptor signaling pathway ...A2A adenosine receptor binding / regulation of translational elongation / 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 / G protein-coupled glutamate receptor signaling pathway / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / astrocyte projection / Class C/3 (Metabotropic glutamate/pheromone receptors) / protein kinase C-activating G protein-coupled receptor signaling pathway / glutamate receptor activity / Neurexins and neuroligins / protein tyrosine kinase activator activity / : / positive regulation of protein tyrosine kinase activity / regulation of synaptic transmission, glutamatergic / protein tyrosine kinase binding / dendritic shaft / locomotory behavior / learning / G protein-coupled receptor activity / postsynaptic density membrane / synapse organization / regulation of protein phosphorylation / Schaffer collateral - CA1 synapse / cognition / cellular response to amyloid-beta / regulation of translation / chemical synaptic transmission / G alpha (q) signalling events / dendritic spine / positive regulation of MAPK cascade / learning or memory / glutamatergic synapse / regulation of DNA-templated transcription / identical protein binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
Authors | Koehl A / Hu H / Feng D / Sun B / Weis WI / Skiniotis GS / Mathiesen JM / Kobilka BK | |||||||||
Funding support | United States, 2 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_0345.map.gz | 59.9 MB | EMDB map data format | |
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Header (meta data) | emd-0345-v30.xml emd-0345.xml | 17.6 KB 17.6 KB | Display Display | EMDB header |
Images | emd_0345.png | 90.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0345 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0345 | HTTPS FTP |
-Related structure data
Related structure data | 6n51MC 0346C 0347C 6n4xC 6n4yC 6n50C 6n52C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_0345.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Metabotropic Glutamate Receptor 5 bound to L-quisqualate and Nb43, primary map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Complex between metabotropic glutamate receptor 5 bound to L-quis...
Entire | Name: Complex between metabotropic glutamate receptor 5 bound to L-quisqualate and Nb43 |
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Components |
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-Supramolecule #1: Complex between metabotropic glutamate receptor 5 bound to L-quis...
Supramolecule | Name: Complex between metabotropic glutamate receptor 5 bound to L-quisqualate and Nb43 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Molecular weight | Theoretical: 220 KDa |
-Macromolecule #1: Metabotropic glutamate receptor 5
Macromolecule | Name: Metabotropic glutamate receptor 5 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 90.484805 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: SERRVVAHMP GDIIIGALFS VHHQPTVDKV HERKCGAVRE QYGIQRVEAM LHTLERINSD PTLLPNITLG CEIRDSCWHS AVALEQSIE FIRDSLISSE EEEGLVRCVD GSSSSFRSKK PIVGVIGPGS SSVAIQVQNL LQLFNIPQIA YSATSMDLSD K TLFKYFMR ...String: SERRVVAHMP GDIIIGALFS VHHQPTVDKV HERKCGAVRE QYGIQRVEAM LHTLERINSD PTLLPNITLG CEIRDSCWHS AVALEQSIE FIRDSLISSE EEEGLVRCVD GSSSSFRSKK PIVGVIGPGS SSVAIQVQNL LQLFNIPQIA YSATSMDLSD K TLFKYFMR VVPSDAQQAR AMVDIVKRYN WTYVSAVHTE GNYGESGMEA FKDMSAKEGI CIAHSYKIYS NAGEQSFDKL LK KLTSHLP KARVVACFCE GMTVRGLLMA MRRLGLAGEF LLLGSDGWAD RYDVTDGYQR EAVGGITIKL QSPDVKWFDD YYL KLRPET NHRNPWFQEF WQHRFQCRLE GFPQENSKYN KTCNSSLTLK THHVQDSKMG FVINAIYSMA YGLHNMQMSL CPGY AGLCD AMKPIDGRKL LESLMKTNFT GVSGDTILFD ENGDSPGRYE IMNFKEMGKD YFDYINVGSW DNGELKMDDD EVWSK KSNI IRSVCSEPCE KGQIKVIRKG EVSCCWTCTP CKENEYVFDE YTCKACQLGS WPTDDLTGCD LIPVQYLRWG DPEPIA AVV FACLGLLATL FVTVVFIIYR DTPVVKSSSR ELCYIILAGI CLGYLCTFCL IAKPKQIYCY LQRIGIGLSP AMSYSAL VT KTNRIARILA GSKKKICTKK PRFMSACAQL VIAFILICIQ LGIIVALFIM EPPDIMHDYP SIREVYLICN TTNLGVVT P LGYNGLLILS CTFYAFKTRN VPANFNEAKY IAFTMYTTCI IWLAFVPIYF GSNYKIITMC FSVSLSATVA LGCMFVPKV YIIL |
-Macromolecule #2: Nanobody 43
Macromolecule | Name: Nanobody 43 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Lama glama (llama) |
Molecular weight | Theoretical: 13.354672 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: QVQLVESGGG LVQAGGSLRL SCAASGRTFT SYAMGWFRQA PGKERESVAA ISSSGGSTHY ADSVKGRFTI SRDNSKNTVY LQMNSLKPE DTAVYYCAAA MYGSRWPDWE YDYWGQGTQV TVSS |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 4 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #4: (S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC ACID
Macromolecule | Name: (S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC ACID type: ligand / ID: 4 / Number of copies: 2 / Formula: QUS |
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Molecular weight | Theoretical: 189.126 Da |
Chemical component information | ChemComp-QUS: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 12 mg/mL | |||||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 200 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 390.0 kPa | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV Details: additional 0.1%OG was added to the sample right before applying sample to grid; 3.5ul sample was applied; blot for 1 second before plunging;. | |||||||||||||||
Details | Sample was mono disperse as assayed by size exclusion chromatography |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Calibrated magnification: 47169 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal magnification: 130000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average exposure time: 8.0 sec. / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
CTF correction | Software - Name: Gctf (ver. 1.06) |
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Startup model | Type of model: OTHER / Details: Ab initio map was generated by VIPER. |
Initial angle assignment | Type: RANDOM ASSIGNMENT / Software - Name: cryoSPARC |
Final angle assignment | Type: PROJECTION MATCHING / Software - Name: RELION (ver. 2.1) |
Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 2.1) / Number images used: 73472 |
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT / Target criteria: Geometry |
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Output model | PDB-6n51: |