+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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Function / homology | Function and homology information Phase 2 - plateau phase / Activation of AMPA receptors / Phase 0 - rapid depolarisation / 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 / LGI-ADAM interactions / COPII-mediated vesicle transport ...Phase 2 - plateau phase / Activation of AMPA receptors / Phase 0 - rapid depolarisation / 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 / LGI-ADAM interactions / COPII-mediated vesicle transport / Trafficking of AMPA receptors / cellular response to amine stimulus / axonal spine / Trafficking of GluR2-containing AMPA receptors / positive regulation of membrane potential / localization within membrane / cellular response to ammonium ion / neurotransmitter receptor transport, postsynaptic endosome to lysosome / L-type voltage-gated calcium channel complex / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / myosin V binding / neuron spine / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / protein phosphatase 2B binding / response to arsenic-containing substance / postsynaptic neurotransmitter receptor diffusion trapping / cellular response to dsRNA / dendritic spine membrane / anchoring junction / long-term synaptic depression / beta-2 adrenergic receptor binding / cellular response to peptide hormone stimulus / protein kinase A binding / neuronal cell body membrane / spinal cord development / response to lithium ion / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / regulation of postsynaptic membrane neurotransmitter receptor levels / immunoglobulin binding / calcium channel regulator activity / neuronal action potential / AMPA glutamate receptor complex / excitatory synapse / ionotropic glutamate receptor complex / adenylate cyclase binding / asymmetric synapse / G-protein alpha-subunit binding / regulation of receptor recycling / voltage-gated calcium channel activity / glutamate receptor binding / regulation of postsynaptic membrane potential / long-term memory / positive regulation of synaptic transmission / response to electrical stimulus / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / cellular response to brain-derived neurotrophic factor stimulus / vesicle-mediated transport / somatodendritic compartment / synapse assembly / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / ionotropic glutamate receptor binding / regulation of membrane potential / positive regulation of synaptic transmission, glutamatergic / response to cocaine / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / dendritic shaft / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / cellular response to amino acid stimulus / postsynaptic density membrane / regulation of synaptic plasticity / modulation of chemical synaptic transmission / Schaffer collateral - CA1 synapse / neuromuscular junction / receptor internalization / synaptic vesicle membrane / response to toxic substance / recycling endosome / cerebral cortex development / small GTPase binding / recycling endosome membrane / G-protein beta-subunit binding / cell-cell junction / synaptic vesicle / presynapse / response to estradiol / presynaptic membrane / cell body / amyloid-beta binding / chemical synaptic transmission / early endosome membrane / postsynapse Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) / Mouse (mice) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Yu J / Rao P / Gouaux E | |||||||||
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 | 26.6 KB 26.6 KB | Display Display | EMDB header |
Images | emd_23284.png | 113.6 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 |
-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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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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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: NOT APPLICABLE |
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Final angle assignment | Type: NOT APPLICABLE |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 157000 |