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Yorodumi- PDB-7mtr: CryoEM Structure of Full-Length mGlu2 Bound to Ago-PAM ADX55164 a... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7mtr | |||||||||
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Title | CryoEM Structure of Full-Length mGlu2 Bound to Ago-PAM ADX55164 and Glutamate | |||||||||
Components | Metabotropic glutamate receptor 2 | |||||||||
Keywords | MEMBRANE PROTEIN/AGONIST / Metabotropic Glutamate Receptor 2 (mGlu2) (mGluR2) / Family C G protein-coupled receptor (GPCR) / Heterotrimeric G protein / CryoEM structure / MEMBRANE PROTEIN / MEMBRANE PROTEIN-AGONIST 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 / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / 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 / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / 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 / regulation of synaptic transmission, glutamatergic / presynaptic modulation of chemical synaptic transmission / response to cocaine / G protein-coupled receptor activity / presynaptic membrane / gene expression / G alpha (i) signalling events / scaffold protein binding / chemical synaptic transmission / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / axon / glutamatergic synapse / dendrite / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Seven, A.B. / Barros-Alvarez, X. / Skiniotis, G. | |||||||||
Funding support | United States, 1items
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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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7mtr.cif.gz | 261.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7mtr.ent.gz | 205.4 KB | Display | PDB format |
PDBx/mmJSON format | 7mtr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7mtr_validation.pdf.gz | 789.4 KB | Display | wwPDB validaton report |
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Full document | 7mtr_full_validation.pdf.gz | 803.3 KB | Display | |
Data in XML | 7mtr_validation.xml.gz | 46.3 KB | Display | |
Data in CIF | 7mtr_validation.cif.gz | 70.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mt/7mtr ftp://data.pdbj.org/pub/pdb/validation_reports/mt/7mtr | HTTPS FTP |
-Related structure data
Related structure data | 23995MC 7mtqC 7mtsC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10978 (Title: CryoEM Structure of Full-Length mGlu2 Bound to Ago-PAM ADX55164 and Glutamate Data size: 3.5 TB Data #1: Unaligned multi-frame micrographs of Full-Length mGlu2 Bound to Ago-PAM ADX55164 and Glutamate [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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-Components
#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 #2: Chemical | #3: Sugar | #4: Chemical | ChemComp-ZQY / | Has ligand of interest | Y | |
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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: Full-length mGlu2 in ago-PAM and L-Glutamate bound-state Type: COMPLEX Details: Metabotropic glutamate receptor 2 bound to ago-PAM ADX55164 and L-Glutamate Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.191 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 |
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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 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 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: dev_4271: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: cryoSPARC / Version: 3.2 / Category: 3D reconstruction | ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 219019 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Highest resolution: 3.3 Å | ||||||||||||||||||||||||
Refine LS restraints |
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