+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23284 | |||||||||
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Title | native AMPA receptor | |||||||||
Map data | ||||||||||
Sample |
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Keywords | neurotransmitter / hippocampus / ion-channel / glycosylation / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Activation of AMPA receptors / negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Synaptic adhesion-like molecules / Cargo concentration in the ER / Unblocking of NMDA receptors, glutamate binding and activation / COPII-mediated vesicle transport / LGI-ADAM interactions ...Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Activation of AMPA receptors / negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Synaptic adhesion-like molecules / Cargo concentration in the ER / Unblocking of NMDA receptors, glutamate binding and activation / COPII-mediated vesicle transport / LGI-ADAM interactions / cellular response to amine stimulus / axonal spine / Trafficking of GluR2-containing AMPA receptors / Trafficking of AMPA receptors / positive regulation of membrane potential / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / localization within membrane / cellular response to ammonium ion / neurotransmitter receptor transport, postsynaptic endosome to lysosome / L-type voltage-gated calcium channel complex / myosin V binding / neuron spine / cellular response to dsRNA / regulation of AMPA receptor activity / protein phosphatase 2B binding / neurotransmitter receptor internalization / response to arsenic-containing substance / postsynaptic neurotransmitter receptor diffusion trapping / nervous system process / dendritic spine membrane / long-term synaptic depression / cellular response to peptide hormone stimulus / beta-2 adrenergic receptor binding / protein kinase A binding / spinal cord development / neuronal cell body membrane / perisynaptic space / AMPA glutamate receptor activity / transmission of nerve impulse / channel regulator activity / response to lithium ion / immunoglobulin binding / regulation of postsynaptic membrane neurotransmitter receptor levels / AMPA glutamate receptor complex / excitatory synapse / adenylate cyclase binding / ionotropic glutamate receptor complex / regulation of postsynaptic membrane potential / postsynaptic density, intracellular component / asymmetric synapse / neuronal action potential / calcium channel regulator activity / regulation of receptor recycling / G-protein alpha-subunit binding / voltage-gated calcium channel activity / glutamate receptor binding / positive regulation of synaptic transmission / response to electrical stimulus / long-term memory / glutamate-gated receptor activity / response to fungicide / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / vesicle-mediated transport / ionotropic glutamate receptor binding / somatodendritic compartment / dendrite membrane / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of synaptic transmission, glutamatergic / regulation of membrane potential / dendritic shaft / response to cocaine / synaptic membrane / synaptic transmission, glutamatergic / long-term synaptic potentiation / cellular response to amino acid stimulus / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / postsynaptic density membrane / modulation of chemical synaptic transmission / neuromuscular junction / Schaffer collateral - CA1 synapse / regulation of synaptic plasticity / receptor internalization / cerebral cortex development / small GTPase binding / response to toxic substance / synaptic vesicle membrane / recycling endosome membrane / G-protein beta-subunit binding / cell-cell junction / synaptic vesicle / response to estradiol / presynapse / presynaptic membrane / amyloid-beta binding / early endosome membrane / cell body Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Yu J / Rao P | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nature / Year: 2021 Title: Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition. Authors: Jie Yu / Prashant Rao / Sarah Clark / Jaba Mitra / Taekjip Ha / Eric Gouaux / Abstract: AMPA-selective glutamate receptors mediate the transduction of signals between the neuronal circuits of the hippocampus. The trafficking, localization, kinetics and pharmacology of AMPA receptors are ...AMPA-selective glutamate receptors mediate the transduction of signals between the neuronal circuits of the hippocampus. The trafficking, localization, kinetics and pharmacology of AMPA receptors are tuned by an ensemble of auxiliary protein subunits, which are integral membrane proteins that associate with the receptor to yield bona fide receptor signalling complexes. Thus far, extensive studies of recombinant AMPA receptor-auxiliary subunit complexes using engineered protein constructs have not been able to faithfully elucidate the molecular architecture of hippocampal AMPA receptor complexes. Here we obtain mouse hippocampal, calcium-impermeable AMPA receptor complexes using immunoaffinity purification and use single-molecule fluorescence and cryo-electron microscopy experiments to elucidate three major AMPA receptor-auxiliary subunit complexes. The GluA1-GluA2, GluA1-GluA2-GluA3 and GluA2-GluA3 receptors are the predominant assemblies, with the auxiliary subunits TARP-γ8 and CNIH2-SynDIG4 non-stochastically positioned at the B'/D' and A'/C' positions, respectively. We further demonstrate how the receptor-TARP-γ8 stoichiometry explains the mechanism of and submaximal inhibition by a clinically relevant, brain-region-specific allosteric inhibitor. | |||||||||
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_23284.map.gz | 483.5 MB | EMDB map data format | |
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Header (meta data) | emd-23284-v30.xml emd-23284.xml | 26.5 KB 26.5 KB | Display Display | EMDB header |
Images | emd_23284.png | 113.6 KB | ||
Filedesc metadata | emd-23284.cif.gz | 8.1 KB | ||
Others | emd_23284_additional_1.map.gz emd_23284_additional_2.map.gz | 483.6 MB 245.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23284 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23284 | HTTPS FTP |
-Validation report
Summary document | emd_23284_validation.pdf.gz | 508.8 KB | Display | EMDB validaton report |
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Full document | emd_23284_full_validation.pdf.gz | 508.3 KB | Display | |
Data in XML | emd_23284_validation.xml.gz | 7.9 KB | Display | |
Data in CIF | emd_23284_validation.cif.gz | 9.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23284 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23284 | HTTPS FTP |
-Related structure data
Related structure data | 7ldeMC 7lddC 7lepC M: atomic model generated by this map C: citing same article (ref.) |
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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_23284.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.00687 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: #2
File | emd_23284_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_23284_additional_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : GluA1/A2-asymmetric-conformation bound to antibody fragments
+Supramolecule #1: GluA1/A2-asymmetric-conformation bound to antibody fragments
+Supramolecule #2: GluA1/A2-asymmetric-conformation
+Supramolecule #3: 11B8 scFv
+Supramolecule #4: 15F1 Fab
+Macromolecule #1: Glutamate receptor 1
+Macromolecule #2: Glutamate receptor
+Macromolecule #3: Protein cornichon homolog 2
+Macromolecule #4: Voltage-dependent calcium channel gamma-8 subunit
+Macromolecule #5: 11B8 scFv
+Macromolecule #6: 15F1 Fab light chain
+Macromolecule #7: 15F1 Fab heavy chain
+Macromolecule #9: {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquino...
+Macromolecule #10: HEXADECANE
+Macromolecule #11: N-OCTANE
+Macromolecule #12: HEPTANE
+Macromolecule #13: DECANE
+Macromolecule #14: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #15: DODECANE
+Macromolecule #16: TETRADECANE
+Macromolecule #17: nonane
+Macromolecule #18: 6-[2-chloro-6-(trifluoromethoxy)phenyl]-1H-benzimidazol-2-ol
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 157000 |
Initial angle assignment | Type: NOT APPLICABLE |
Final angle assignment | Type: NOT APPLICABLE |