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- PDB-5weo: Activated GluA2 complex bound to glutamate, cyclothiazide, and ST... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5weo | ||||||||||||||||||
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Title | Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin | ||||||||||||||||||
![]() | Glutamate receptor 2,Voltage-dependent calcium channel gamma-2 subunit chimera | ||||||||||||||||||
![]() | TRANSPORT PROTEIN / Ion channel | ||||||||||||||||||
Function / homology | ![]() Presynaptic depolarization and calcium channel opening / LGI-ADAM interactions / regulation of postsynaptic neurotransmitter receptor activity / Trafficking of AMPA receptors / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / cerebellar mossy fiber / neurotransmitter receptor transport, postsynaptic endosome to lysosome / regulation of AMPA receptor activity / neurotransmitter receptor internalization ...Presynaptic depolarization and calcium channel opening / LGI-ADAM interactions / regulation of postsynaptic neurotransmitter receptor activity / Trafficking of AMPA receptors / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / cerebellar mossy fiber / neurotransmitter receptor transport, postsynaptic endosome to lysosome / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / membrane hyperpolarization / postsynaptic neurotransmitter receptor diffusion trapping / nervous system process / protein targeting to membrane / neurotransmitter receptor localization to postsynaptic specialization membrane / voltage-gated calcium channel complex / neuromuscular junction development / spine synapse / dendritic spine neck / dendritic spine head / Activation of AMPA receptors / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / regulation of postsynaptic membrane neurotransmitter receptor levels / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / immunoglobulin binding / membrane depolarization / AMPA glutamate receptor complex / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / cellular response to glycine / asymmetric synapse / regulation of receptor recycling / voltage-gated calcium channel activity / Unblocking of NMDA receptors, glutamate binding and activation / glutamate receptor binding / positive regulation of synaptic transmission / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / regulation of synaptic transmission, glutamatergic / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / cytoskeletal protein binding / ionotropic glutamate receptor signaling pathway / dendrite cytoplasm / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic / SNARE binding / dendritic shaft / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / regulation of membrane potential / protein tetramerization / postsynaptic density membrane / ionotropic glutamate receptor binding / Schaffer collateral - CA1 synapse / modulation of chemical synaptic transmission / establishment of protein localization / terminal bouton / receptor internalization / cerebral cortex development / synaptic vesicle membrane / response to calcium ion / synaptic vesicle / presynapse / presynaptic membrane / signaling receptor activity / amyloid-beta binding / growth cone / scaffold protein binding / chemical synaptic transmission / postsynaptic membrane / perikaryon / dendritic spine / postsynaptic density / neuron projection / axon / neuronal cell body / glutamatergic synapse / synapse / dendrite / protein-containing complex binding / endoplasmic reticulum membrane / protein kinase binding / cell surface / endoplasmic reticulum / protein-containing complex / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.2 Å | ||||||||||||||||||
![]() | Twomey, E.C. / Yelshanskaya, M.V. / Grassucci, R.A. / Frank, J. / Sobolevsky, A.I. | ||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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. | ||||||||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 687.3 KB | Display | ![]() |
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PDB format | ![]() | 570.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 106.8 KB | Display | |
Data in CIF | ![]() | 159.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8823MC ![]() 8819C ![]() 8820C ![]() 8821C ![]() 8822C ![]() 5wekC ![]() 5welC ![]() 5wemC ![]() 5wenC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 115501.969 Da / Num. of mol.: 4 Fragment: UNP P19491 residues 25-847, UNP O88602 2-208 linked via LINKER GT Mutation: N241E, V382L, G384E, N385D, V758L Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() Gene: Gria2, Glur2, Cacng2, Stg / Cell line (production host): HEK293 gnti- / Production host: ![]() #2: Chemical | ChemComp-GLU / #3: Chemical | ChemComp-CYZ / |
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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 |
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Sample preparation
Component | Name: Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin |
Specimen support | Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: C-flat-1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 K |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Average exposure time: 8 sec. / Electron dose: 55 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
Image scans | Movie frames/image: 40 |
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Processing
Software | Name: PHENIX / Version: 1.11.1_2575: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 69207 Details: TMD map uploaded under additional files is at 4.0 angstrom resolution. Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||
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