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Yorodumi- PDB-7oce: Resting state GluA1/A2 AMPA receptor in complex with TARP gamma 8... -
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-Basic information
Entry | Database: PDB / ID: 7oce | |||||||||
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Title | Resting state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and CNIH2 (LBD-TMD) | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / AMPAR / ion channels / neurotransmission | |||||||||
Function / homology | Function and homology information negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Phase 2 - plateau phase / Phase 0 - rapid depolarisation / Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / localization within membrane ...negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Phase 2 - plateau phase / Phase 0 - rapid depolarisation / Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / localization within membrane / chemical synaptic transmission, postsynaptic / cellular response to ammonium ion / neurotransmitter receptor transport, postsynaptic endosome to lysosome / L-type voltage-gated calcium channel complex / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / LGI-ADAM interactions / neuron spine / myosin V binding / Trafficking of AMPA receptors / regulation of AMPA receptor activity / neurotransmitter receptor internalization / dendritic spine membrane / channel regulator activity / protein phosphatase 2B binding / postsynaptic neurotransmitter receptor diffusion trapping / response to arsenic-containing substance / cellular response to dsRNA / Synaptic adhesion-like molecules / long-term synaptic depression / cellular response to peptide hormone stimulus / beta-2 adrenergic receptor binding / neuronal cell body membrane / spine synapse / spinal cord development / dendritic spine head / dendritic spine neck / Activation of AMPA receptors / response to lithium ion / cellular response to glycine / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / protein kinase A binding / regulation of postsynaptic membrane neurotransmitter receptor levels / regulation of NMDA receptor activity / Trafficking of GluR2-containing AMPA receptors / immunoglobulin binding / calcium channel regulator activity / neuronal action potential / AMPA glutamate receptor complex / kainate selective glutamate receptor activity / excitatory synapse / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / adenylate cyclase binding / cellular response to organic cyclic compound / asymmetric synapse / G-protein alpha-subunit binding / regulation of receptor recycling / Unblocking of NMDA receptors, glutamate binding and activation / voltage-gated calcium channel activity / long-term memory / glutamate receptor binding / regulation of postsynaptic membrane potential / positive regulation of synaptic transmission / response to electrical stimulus / presynaptic active zone membrane / response to fungicide / glutamate-gated receptor activity / vesicle-mediated transport / regulation of synaptic transmission, glutamatergic / cellular response to brain-derived neurotrophic factor stimulus / somatodendritic compartment / synapse assembly / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / ionotropic glutamate receptor binding / regulation of membrane potential / cytoskeletal protein binding / ionotropic glutamate receptor signaling pathway / monoatomic ion transmembrane transport / dendrite cytoplasm / positive regulation of synaptic transmission, glutamatergic / SNARE binding / response to cocaine / dendritic shaft / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / cellular response to amino acid stimulus / postsynaptic density membrane / protein tetramerization / regulation of synaptic plasticity / neuromuscular junction / modulation of chemical synaptic transmission / Schaffer collateral - CA1 synapse / response to toxic substance / establishment of protein localization / terminal bouton Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Zhang, D. / Watson, J.F. / Matthews, P.M. / Cais, O. / Greger, I.H. | |||||||||
Funding support | 2items
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Citation | Journal: Nature / Year: 2021 Title: Gating and modulation of a hetero-octameric AMPA glutamate receptor. Authors: Danyang Zhang / Jake F Watson / Peter M Matthews / Ondrej Cais / Ingo H Greger / Abstract: AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning. A diverse array of AMPAR signalling complexes are ...AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1-GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties. | |||||||||
History |
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-Structure visualization
Movie |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7oce.cif.gz | 466.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7oce.ent.gz | 353.8 KB | Display | PDB format |
PDBx/mmJSON format | 7oce.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/oc/7oce ftp://data.pdbj.org/pub/pdb/validation_reports/oc/7oce | HTTPS FTP |
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-Related structure data
Related structure data | 12805MC 7ocaC 7occC 7ocdC 7ocfC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Glutamate receptor ... , 2 types, 4 molecules ACBD
#1: Protein | Mass: 102661.930 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gria1, Glur1 / Plasmid: pRK5 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: P19490 #2: Protein | Mass: 96247.055 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gria2, Glur2 / Plasmid: pRK5 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: P19491 |
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-Protein , 2 types, 4 molecules GEIJ
#3: Protein | Mass: 22000.605 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Cnih2 / Plasmid: pRK5 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q5BJU5 #4: Protein | Mass: 43518.957 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Cacng8 / Plasmid: pRK5 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q8VHW5 |
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-Non-polymers , 3 types, 52 molecules
#5: Chemical | ChemComp-E2Q / #6: Chemical | ChemComp-PC1 / #7: Chemical | |
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-Details
Has ligand of interest | N |
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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: GluA1/A2 heterotetramer in complex with auxiliary subunits TARP gamma 8 and CNIH2 Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT | ||||||||||||||||||||
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Molecular weight | Value: 0.527 MDa / Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: Rattus norvegicus (Norway rat) | ||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Purified protein was incubated with 100 uM NBQX for at least 30 min on ice before freezing | ||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-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 / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 2.5 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 218320 / Algorithm: FOURIER SPACE / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 113 / Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||
Atomic model building |
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