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- PDB-8ssa: Structure of AMPA receptor GluA2 complex with auxiliary subunits ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8ssa | |||||||||||||||
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Title | Structure of AMPA receptor GluA2 complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to glutamate and channel blocker spermidine (desensitized state) | |||||||||||||||
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![]() | SIGNALING PROTEIN / AMPA receptor / spermidine / TARP gamma-5 / cornichon-2 | |||||||||||||||
Function / homology | ![]() postsynaptic neurotransmitter receptor diffusion trapping / channel regulator activity / regulation of AMPA receptor activity / Cargo concentration in the ER / COPII-mediated vesicle transport / spine synapse / dendritic spine neck / dendritic spine head / cellular response to amine stimulus / Activation of AMPA receptors ...postsynaptic neurotransmitter receptor diffusion trapping / channel regulator activity / regulation of AMPA receptor activity / Cargo concentration in the ER / COPII-mediated vesicle transport / spine synapse / dendritic spine neck / dendritic spine head / cellular response to amine stimulus / Activation of AMPA receptors / perisynaptic space / ligand-gated monoatomic cation channel activity / AMPA glutamate receptor activity / transmission of nerve impulse / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / kainate selective glutamate receptor activity / AMPA glutamate receptor complex / cellular response to glycine / extracellularly glutamate-gated ion channel activity / ionotropic glutamate receptor complex / immunoglobulin binding / asymmetric synapse / conditioned place preference / regulation of receptor recycling / glutamate receptor binding / Unblocking of NMDA receptors, glutamate binding and activation / positive regulation of synaptic transmission / voltage-gated calcium channel activity / response to fungicide / regulation of synaptic transmission, glutamatergic / glutamate-gated receptor activity / cytoskeletal protein binding / vesicle-mediated transport / regulation of long-term synaptic depression / extracellular ligand-gated monoatomic ion channel activity / cellular response to brain-derived neurotrophic factor stimulus / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / somatodendritic compartment / dendrite membrane / endoplasmic reticulum-Golgi intermediate compartment membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / ionotropic glutamate receptor binding / dendrite cytoplasm / ionotropic glutamate receptor signaling pathway / positive regulation of synaptic transmission, glutamatergic / SNARE binding / dendritic shaft / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic transmission, glutamatergic / PDZ domain binding / protein tetramerization / establishment of protein localization / synaptic membrane / ER to Golgi transport vesicle membrane / postsynaptic density membrane / modulation of chemical synaptic transmission / cerebral cortex development / receptor internalization / Schaffer collateral - CA1 synapse / terminal bouton / synaptic vesicle membrane / synaptic vesicle / signaling receptor activity / presynapse / amyloid-beta binding / presynaptic membrane / growth cone / scaffold protein binding / perikaryon / chemical synaptic transmission / dendritic spine / postsynaptic membrane / neuron projection / postsynaptic density / axon / signaling receptor binding / external side of plasma membrane / neuronal cell body / synapse / dendrite / endoplasmic reticulum membrane / protein kinase binding / protein-containing complex binding / glutamatergic synapse / 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: 3.88 Å | |||||||||||||||
![]() | Gangwar, S.P. / Yen, L.Y. / Yelshanskaya, M.V. / Sobolevsky, A.I. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Modulation of GluA2-γ5 synaptic complex desensitization, polyamine block and antiepileptic perampanel inhibition by auxiliary subunit cornichon-2. Authors: Shanti Pal Gangwar / Laura Y Yen / Maria V Yelshanskaya / Aryeh Korman / Drew R Jones / Alexander I Sobolevsky / ![]() Abstract: Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat ...Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat neuropsychiatric and neurological disorders, including epilepsy. Here we present cryogenic-electron microscopy structures of rat GluA2 AMPAR complexes with inhibitory mouse γ5 and potentiating human cornichon-2 (CNIH2) auxiliary subunits. CNIH2 appears to destabilize the desensitized state of the complex by reducing the separation of the upper lobes in ligand-binding domain dimers. At the same time, CNIH2 stabilizes binding of polyamine spermidine to the selectivity filter of the closed ion channel. Nevertheless, CNIH2, and to a lesser extent γ5, attenuate polyamine block of the open channel and reduce the potency of the antiepileptic drug perampanel that inhibits the synaptic complex allosterically by binding to sites in the ion channel extracellular collar. These findings illustrate the fine-tuning of synaptic complex structure and function in an auxiliary subunit-dependent manner, which is critical for the study of brain region-specific neurotransmission and design of therapeutics for disease treatment. | |||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 690.8 KB | Display | ![]() |
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PDB format | ![]() | 560.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 2.2 MB | Display | ![]() |
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Full document | ![]() | 2.2 MB | Display | |
Data in XML | ![]() | 126.5 KB | Display | |
Data in CIF | ![]() | 182.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 40749MC ![]() 8ss2C ![]() 8ss3C ![]() 8ss4C ![]() 8ss5C ![]() 8ss6C ![]() 8ss7C ![]() 8ss8C ![]() 8ss9C ![]() 8ssbC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 114978.859 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 18948.420 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Chemical | ChemComp-PCW / #4: Chemical | ChemComp-GLU / #5: Chemical | ChemComp-SPD / | Has ligand of interest | Y | Has protein modification | Y | |
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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: GluA2-TARP gamma5-cornichon-2 / Type: COMPLEX Details: Structure of AMPA receptor GluA2 complex with auxiliary subunits TARP gamma-5 and cornichon-2 bound to competitive antagonist ZK and channel blocker spermidine (closed state) Entity ID: #1-#2 / Source: MULTIPLE SOURCES | |||||||||||||||||||||||||
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 4.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Protein extracted and purified in detergent micelle | |||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K / Details: vitrification carried out in nitrogen atmosphere |
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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 / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 58 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.88 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 58186 / Symmetry type: POINT | ||||||||||||||||||||||||
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