[English] 日本語
![](img/lk-miru.gif)
- PDB-6dm1: Open state GluA2 in complex with STZ and blocked by NASPM, after ... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 6dm1 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Open state GluA2 in complex with STZ and blocked by NASPM, after micelle signal subtraction | ||||||||||||
![]() | Glutamate receptor 2,Voltage-dependent calcium channel gamma-2 subunit | ||||||||||||
![]() | TRANSPORT PROTEIN / Ion channel | ||||||||||||
Function / homology | ![]() LGI-ADAM interactions / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / Presynaptic depolarization and calcium channel opening / cerebellar mossy fiber / neurotransmitter receptor transport, postsynaptic endosome to lysosome / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / membrane hyperpolarization ...LGI-ADAM interactions / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / Presynaptic depolarization and calcium channel opening / cerebellar mossy fiber / neurotransmitter receptor transport, postsynaptic endosome to lysosome / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / membrane hyperpolarization / Trafficking of AMPA receptors / postsynaptic neurotransmitter receptor diffusion trapping / 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 / 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 / protein tetramerization / postsynaptic density membrane / ionotropic glutamate receptor binding / Schaffer collateral - CA1 synapse / modulation of chemical synaptic transmission / establishment of protein localization / receptor internalization / terminal bouton / cerebral cortex development / synaptic vesicle membrane / response to calcium ion / endocytic vesicle membrane / 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. / Vassilevski, A.A. / Sobolevsky, A.I. | ||||||||||||
Funding support | ![]()
| ||||||||||||
![]() | ![]() Title: Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors. Authors: Edward C Twomey / Maria V Yelshanskaya / Alexander A Vassilevski / Alexander I Sobolevsky / ![]() ![]() Abstract: AMPA receptors mediate fast excitatory neurotransmission and are critical for CNS development and function. Calcium-permeable subsets of AMPA receptors are strongly implicated in acute and chronic ...AMPA receptors mediate fast excitatory neurotransmission and are critical for CNS development and function. Calcium-permeable subsets of AMPA receptors are strongly implicated in acute and chronic neurological disorders. However, despite the clinical importance, the therapeutic landscape for specifically targeting them, and not the calcium-impermeable AMPA receptors, remains largely undeveloped. To address this problem, we used cryo-electron microscopy and electrophysiology to investigate the mechanisms by which small-molecule blockers selectively inhibit ion channel conductance in calcium-permeable AMPA receptors. We determined the structures of calcium-permeable GluA2 AMPA receptor complexes with the auxiliary subunit stargazin bound to channel blockers, including the orb weaver spider toxin AgTx-636, the spider toxin analog NASPM, and the adamantane derivative IEM-1460. Our structures provide insights into the architecture of the blocker binding site and the mechanism of trapping, which are critical for development of small molecules that specifically target calcium-permeable AMPA receptors. | ||||||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 687.8 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 572.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 103.6 KB | Display | |
Data in CIF | ![]() | 155.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7961MC ![]() 7959C ![]() 7960C ![]() 7962C ![]() 6dlzC ![]() 6dm0C ![]() 6o9gC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 115178.531 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: Gria2, Glur2, CACNG2 / Production host: ![]() #2: Chemical | ChemComp-GLU / #3: Chemical | ChemComp-CYZ / #4: Chemical | ChemComp-GYY / | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: Open state GluA2 in complex with STZ and blocked by NASPM, after micelle signal subtraction Type: COMPLEX Details: The full-map (non-TMD-directed) is included as a supplemental file Entity ID: #1 / Source: RECOMBINANT |
---|---|
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: Open state GluA2 in complex with STZ and blocked by NASPM, after micelle signal subtraction |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 K |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
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 |
-
Processing
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: 39835 / Details: Full map (supplemental file) is 4.4 angstrom. / Symmetry type: POINT |
Atomic model building | Space: REAL |