|Entry||Database: EMDB / ID: EMD-8823|
|Title||Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin|
|Sample||Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin|
|Function / homology|
Function and homology information
eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / neurotransmitter receptor transport, postsynaptic endosome to lysosome / neurotransmitter receptor internalization / regulation of postsynaptic membrane neurotransmitter receptor levels / cerebellar mossy fiber / neurotransmitter receptor localization to postsynaptic specialization membrane / regulation of postsynaptic neurotransmitter receptor activity / positive regulation of AMPA receptor activity / regulation of AMPA receptor activity ...eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / neurotransmitter receptor transport, postsynaptic endosome to lysosome / neurotransmitter receptor internalization / regulation of postsynaptic membrane neurotransmitter receptor levels / cerebellar mossy fiber / neurotransmitter receptor localization to postsynaptic specialization membrane / regulation of postsynaptic neurotransmitter receptor activity / positive regulation of AMPA receptor activity / regulation of AMPA receptor activity / postsynaptic neurotransmitter receptor diffusion trapping / membrane hyperpolarization / protein targeting to membrane / voltage-gated calcium channel complex / somatodendritic compartment / neuromuscular junction development / membrane depolarization / transmission of nerve impulse / nervous system process / voltage-gated calcium channel activity / AMPA glutamate receptor activity / asymmetric synapse / ionotropic glutamate receptor binding / kainate selective glutamate receptor activity / AMPA glutamate receptor complex / ionotropic glutamate receptor complex / response to lithium ion / regulation of receptor recycling / immunoglobulin binding / positive regulation of synaptic transmission / integral component of postsynaptic membrane / regulation of membrane potential / SNARE binding / ionotropic glutamate receptor activity / response to fungicide / regulation of synaptic transmission, glutamatergic / integral component of postsynaptic density membrane / glutamate receptor activity / transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential / ionotropic glutamate receptor signaling pathway / synaptic transmission, glutamatergic / cytoskeletal protein binding / synaptic vesicle membrane / postsynaptic density membrane / dendritic shaft / hippocampal mossy fiber to CA3 synapse / receptor internalization / dendrite cytoplasm / integral component of presynaptic membrane / Schaffer collateral - CA1 synapse / PDZ domain binding / presynaptic membrane / terminal bouton / response to calcium ion / protein tetramerization / establishment of protein localization / modulation of chemical synaptic transmission / growth cone / chemical synaptic transmission / amyloid-beta binding / postsynaptic membrane / ATPase binding / perikaryon / signaling receptor activity / dendritic spine / postsynaptic density / synapse / cell junction / glutamatergic synapse / dendrite / neuronal cell body / endoplasmic reticulum membrane / protein kinase binding / integral component of plasma membrane / cell surface / protein-containing complex / identical protein binding / plasma membrane / cytosol
PMP-22/EMP/MP20/Claudin superfamily / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Receptor, ligand binding region / Ionotropic glutamate receptor, metazoa / Ionotropic glutamate receptor / Voltage-dependent calcium channel, gamma subunit / Voltage-dependent calcium channel, gamma-2 subunit / Periplasmic binding protein-like I
Voltage-dependent calcium channel gamma-2 subunit / Glutamate receptor 2
|Biological species||Rattus norvegicus (Norway rat) / Mus musculus (house mouse)|
|Method||single particle reconstruction / cryo EM / Resolution: 4.2 Å|
|Authors||Twomey EC / Yelshanskaya MV / Grassucci RA / Frank J / Sobolevsky AI|
|Funding support|| United States, 5 items |
|Citation||Journal: Nature / Year: 2017|
Title: Channel opening and gating mechanism in AMPA-subtype glutamate receptors.
Authors: Edward C Twomey / Maria V Yelshanskaya / Robert A Grassucci / Joachim Frank / Alexander I Sobolevsky /
Abstract: AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission throughout the central nervous system. Gated by the ...AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission throughout the central nervous system. Gated by the neurotransmitter glutamate, AMPA receptors are critical for synaptic strength, and dysregulation of AMPA receptor-mediated signalling is linked to numerous neurological diseases. Here we use cryo-electron microscopy to solve the structures of AMPA receptor-auxiliary subunit complexes in the apo, antagonist- and agonist-bound states and determine the iris-like mechanism of ion channel opening. The ion channel selectivity filter is formed by the extended portions of the re-entrant M2 loops, while the helical portions of M2 contribute to extensive hydrophobic interfaces between AMPA receptor subunits in the ion channel. We show how the permeation pathway changes upon channel opening and identify conformational changes throughout the entire AMPA receptor that accompany activation and desensitization. Our findings provide a framework for understanding gating across the family of ionotropic glutamate receptors and the role of AMPA receptors in excitatory neurotransmission.
|Validation Report||PDB-ID: 5weo|
SummaryFull reportAbout validation report
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_8823.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 1.08 Å|
|Symmetry||Space group: 1|
CCP4 map header:
-Entire Activated GluA2 complex bound to glutamate, cyclothiazide, and ST...
|Entire||Name: Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin|
Number of components: 4
-Component #1: protein, Activated GluA2 complex bound to glutamate, cyclothiazid...
|Protein||Name: Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin|
Recombinant expression: No
|Source||Species: Rattus norvegicus (Norway rat)|
|Source (engineered)||Expression System: Homo sapiens (human) / Cell of expression system: HEK293 gnti-|
-Component #2: protein, Glutamate receptor 2,Voltage-dependent calcium channel g...
|Protein||Name: Glutamate receptor 2,Voltage-dependent calcium channel gamma-2 subunit chimera|
Number of Copies: 4 / Recombinant expression: No
|Mass||Theoretical: 115.501969 kDa|
|Source||Species: Mus musculus (house mouse)|
|Source (engineered)||Expression System: Homo sapiens (human)|
-Component #3: ligand, GLUTAMIC ACID
|Ligand||Name: GLUTAMIC ACID / Number of Copies: 4 / Recombinant expression: No|
|Mass||Theoretical: 0.147129 kDa|
-Component #4: ligand, CYCLOTHIAZIDE
|Ligand||Name: CYCLOTHIAZIDE / Number of Copies: 4 / Recombinant expression: No|
|Mass||Theoretical: 0.389878 kDa|
|Specimen||Specimen state: Particle / Method: cryo EM|
|Sample solution||Specimen conc.: 4 mg/mL / pH: 8|
|Vitrification||Instrument: FEI VITROBOT MARK IV / 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: 55 e/Å2 / Illumination mode: SPOT SCAN|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Camera||Detector: GATAN K2 SUMMIT (4k x 4k)|
|Processing||Method: single particle reconstruction / Applied symmetry: C2 (2 fold cyclic) / Number of projections: 69207|
|3D reconstruction||Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF|
Details: TMD map uploaded under additional files is at 4.0 angstrom resolution.
-Atomic model buiding
|Modeling #1||Refinement space: REAL|
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