|Entry||Database: EMDB / ID: EMD-0431|
|Title||Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM|
|Sample||Native A2AxA1A2 complex bound with MPQX|
|Function / homology|
Function and homology information
cellular response to amine stimulus / axonal spine / positive regulation of membrane potential / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / neurotransmitter receptor transport, postsynaptic endosome to lysosome / dendritic spine membrane / regulation of postsynaptic membrane neurotransmitter receptor levels / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / small GTPase binding ...cellular response to amine stimulus / axonal spine / positive regulation of membrane potential / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / neurotransmitter receptor transport, postsynaptic endosome to lysosome / dendritic spine membrane / regulation of postsynaptic membrane neurotransmitter receptor levels / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / small GTPase binding / positive regulation of AMPA receptor activity / cerebellar mossy fiber / regulation of AMPA receptor activity / neuron spine / neurotransmitter receptor internalization / neurotransmitter receptor localization to postsynaptic specialization membrane / postsynaptic neurotransmitter receptor diffusion trapping / myosin V binding / long-term synaptic depression / membrane hyperpolarization / neuronal action potential / cellular response to dsRNA / response to arsenic-containing substance / calcium channel regulator activity / regulation of postsynaptic membrane potential / protein kinase A binding / protein targeting to membrane / voltage-gated calcium channel complex / nervous system process / beta-2 adrenergic receptor binding / transmission of nerve impulse / G-protein beta-subunit binding / neuromuscular junction development / membrane depolarization / dendrite membrane / perisynaptic space / spinal cord development / AMPA glutamate receptor activity / voltage-gated calcium channel activity / asymmetric synapse / G-protein alpha-subunit binding / ionotropic glutamate receptor binding / adenylate cyclase binding / cellular response to peptide hormone stimulus / extracellularly glutamate-gated ion channel activity / AMPA glutamate receptor complex / kainate selective glutamate receptor activity / excitatory synapse / synaptic transmission, glutamatergic / ionotropic glutamate receptor complex / response to lithium ion / long-term memory / regulation of receptor recycling / glutamate receptor binding / immunoglobulin binding / somatodendritic compartment / positive regulation of synaptic transmission / integral component of postsynaptic density membrane / ionotropic glutamate receptor activity / regulation of synaptic transmission, glutamatergic / response to cocaine / response to fungicide / SNARE binding / cytoskeletal protein binding / response to electrical stimulus / synaptic membrane / transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential / response to peptide hormone / cellular response to organic cyclic compound / ionotropic glutamate receptor signaling pathway / synaptic vesicle membrane / hippocampal mossy fiber to CA3 synapse / dendritic shaft / postsynaptic density membrane / ligand-gated ion channel activity / regulation of synaptic plasticity / cellular response to amino acid stimulus / Schaffer collateral - CA1 synapse / regulation of membrane potential / integral component of presynaptic membrane / PDZ domain binding / dendrite cytoplasm / response to toxic substance / receptor internalization / modulation of chemical synaptic transmission / protein tetramerization / presynaptic membrane / neuromuscular junction / recycling endosome / terminal bouton / response to organic cyclic compound / cellular response to growth factor stimulus / establishment of protein localization / response to calcium ion / postsynapse / recycling endosome membrane / growth cone / cell-cell junction / postsynaptic membrane / chemical synaptic transmission
Receptor, ligand binding region / Ionotropic glutamate receptor / Ionotropic glutamate receptor, metazoa / Periplasmic binding protein-like I / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Voltage-dependent calcium channel, gamma subunit / Voltage-dependent calcium channel, gamma-2 subunit / PMP-22/EMP/MP20/Claudin superfamily
Glutamate receptor 1 / Glutamate receptor 2 / Voltage-dependent calcium channel gamma-2 subunit
|Biological species||Rattus norvegicus (Norway rat)|
|Method||single particle reconstruction / cryo EM / Resolution: 23 Å|
|Authors||Zhao Y / Gouaux E|
|Citation||Journal: Science / Year: 2019|
Title: Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM.
Authors: Yan Zhao / Shanshuang Chen / Adam C Swensen / Wei-Jun Qian / Eric Gouaux /
Abstract: Glutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric ...Glutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric assemblies composed of four subunits, GluA1-GluA4. Despite decades of study, the subunit composition, subunit arrangement, and molecular structure of native AMPA receptors remain unknown. Here we elucidate the structures of 10 distinct native AMPA receptor complexes by single-particle cryo-electron microscopy (cryo-EM). We find that receptor subunits are arranged nonstochastically, with the GluA2 subunit preferentially occupying the B and D positions of the tetramer and with triheteromeric assemblies comprising a major population of native AMPA receptors. Cryo-EM maps define the structure for S2-M4 linkers between the ligand-binding and transmembrane domains, suggesting how neurotransmitter binding is coupled to ion channel gating.
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_0431.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 1.72 Å|
|Symmetry||Space group: 1|
CCP4 map header:
-Entire Native A2AxA1A2 complex bound with MPQX
|Entire||Name: Native A2AxA1A2 complex bound with MPQX / Number of components: 1|
-Component #1: protein, Native A2AxA1A2 complex bound with MPQX
|Protein||Name: Native A2AxA1A2 complex bound with MPQX / Recombinant expression: No|
|Source||Species: Rattus norvegicus (Norway rat)|
|Specimen||Specimen state: Particle / Method: cryo EM|
|Sample solution||Specimen conc.: 4 mg/mL / pH: 8|
|Vitrification||Cryogen name: ETHANE / Temperature: 295 K / Humidity: 100 %|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Imaging||Microscope: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 54 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Camera||Detector: GATAN K2 SUMMIT (4k x 4k)|
|Processing||Method: single particle reconstruction / Number of projections: 5900|
|3D reconstruction||Software: RELION / Resolution: 23 Å / Resolution method: FSC 0.143 CUT-OFF|
-Atomic model buiding
|Modeling #1||Refinement protocol: rigid body / Refinement space: REAL|
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