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Yorodumi- PDB-7tnk: Complex GNNN of AMPA-subtype iGluR GluA2 in complex with auxiliar... -
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-Basic information
Entry | Database: PDB / ID: 7tnk | |||||||||||||||
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Title | Complex GNNN of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM) | |||||||||||||||
Components | Isoform Flip of Glutamate receptor 2,Voltage-dependent calcium channel gamma-3 subunit chimera | |||||||||||||||
Keywords | MEMBRANE PROTEIN / AMPA / iGluR / Stargazin / cryo-EM / complex / agonist / positive allosteric modulator / subconductance level / opening / gating / glutamate | |||||||||||||||
Function / homology | Function and homology information neurotransmitter receptor transport, postsynaptic endosome to lysosome / LGI-ADAM interactions / Trafficking of AMPA receptors / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / postsynaptic neurotransmitter receptor diffusion trapping / neurotransmitter receptor localization to postsynaptic specialization membrane / spine synapse / dendritic spine neck ...neurotransmitter receptor transport, postsynaptic endosome to lysosome / LGI-ADAM interactions / Trafficking of AMPA receptors / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / postsynaptic neurotransmitter receptor diffusion trapping / neurotransmitter receptor localization to postsynaptic specialization membrane / spine synapse / dendritic spine neck / dendritic spine head / Activation of AMPA receptors / response to lithium ion / perisynaptic space / cellular response to glycine / transmission of nerve impulse / AMPA glutamate receptor activity / Trafficking of GluR2-containing AMPA receptors / immunoglobulin binding / AMPA glutamate receptor complex / kainate selective glutamate receptor activity / excitatory synapse / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / asymmetric synapse / protein targeting / regulation of receptor recycling / Unblocking of NMDA receptors, glutamate binding and activation / voltage-gated calcium channel activity / glutamate receptor binding / positive regulation of synaptic transmission / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / regulation of synaptic transmission, glutamatergic / cellular response to brain-derived neurotrophic factor stimulus / somatodendritic compartment / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / ionotropic glutamate receptor binding / ionotropic glutamate receptor signaling pathway / dendrite cytoplasm / cytoskeletal protein binding / positive regulation of synaptic transmission, glutamatergic / SNARE binding / dendritic shaft / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / postsynaptic density membrane / protein tetramerization / modulation of chemical synaptic transmission / Schaffer collateral - CA1 synapse / establishment of protein localization / protein localization / terminal bouton / receptor internalization / synaptic vesicle membrane / cerebral cortex development / synaptic vesicle / presynapse / signaling receptor activity / presynaptic membrane / amyloid-beta binding / growth cone / perikaryon / chemical synaptic transmission / postsynaptic membrane / scaffold protein binding / dendritic spine / postsynaptic density / neuron projection / axon / dendrite / neuronal cell body / glutamatergic synapse / synapse / protein-containing complex binding / endoplasmic reticulum membrane / protein kinase binding / cell surface / endoplasmic reticulum / protein-containing complex / membrane / identical protein binding / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.5 Å | |||||||||||||||
Authors | Yelshanskaya, M.V. / Sobolevsky, A.I. | |||||||||||||||
Funding support | United States, 4items
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Citation | Journal: Nature / Year: 2022 Title: Opening of glutamate receptor channel to subconductance levels. Authors: Maria V Yelshanskaya / Dhilon S Patel / Christopher M Kottke / Maria G Kurnikova / Alexander I Sobolevsky / Abstract: Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that open their pores in response to binding of the agonist glutamate. An ionic current through a single iGluR channel ...Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that open their pores in response to binding of the agonist glutamate. An ionic current through a single iGluR channel shows up to four discrete conductance levels (O1-O4). Higher conductance levels have been associated with an increased number of agonist molecules bound to four individual ligand-binding domains (LBDs). Here we determine structures of a synaptic complex of AMPA-subtype iGluR and the auxiliary subunit γ2 in non-desensitizing conditions with various occupancy of the LBDs by glutamate. We show that glutamate binds to LBDs of subunits B and D only after it is already bound to at least the same number of LBDs that belong to subunits A and C. Our structures combined with single-channel recordings, molecular dynamics simulations and machine-learning analysis suggest that channel opening requires agonist binding to at least two LBDs. Conversely, agonist binding to all four LBDs does not guarantee maximal channel conductance and favours subconductance states O1 and O2, with O3 and O4 being rare and not captured structurally. The lack of subunit independence and low efficiency coupling of glutamate binding to channel opening underlie the gating of synaptic complexes to submaximal conductance levels, which provide a potential for upregulation of synaptic activity. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7tnk.cif.gz | 449.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7tnk.ent.gz | 358.3 KB | Display | PDB format |
PDBx/mmJSON format | 7tnk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tn/7tnk ftp://data.pdbj.org/pub/pdb/validation_reports/tn/7tnk | HTTPS FTP |
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-Related structure data
Related structure data | 26012MC 7tnjC 7tnlC 7tnmC 7tnnC 7tnoC 7tnpC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 115444.922 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gria2, Glur2, Cacng3 / Production host: Homo sapiens (human) / References: UniProt: P19491, UniProt: Q8VHX0 #2: Chemical | ChemComp-GLU / | #3: Chemical | ChemComp-CYZ / Has ligand of interest | 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 |
-Sample preparation
Component | Name: Ionotropic glutamate receptor GluA2 in complex with auxiliary subunit gamma2 or Stargazin Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 58.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING ONLY |
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3D reconstruction | Resolution: 4.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 40058 / Symmetry type: POINT |