+Open data
-Basic information
Entry | Database: PDB / ID: 7occ | |||||||||
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Title | NTD of resting state GluA1/A2 heterotertramer | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / AMPAR / ion channels / neurotransmission | |||||||||
Function / homology | Function and homology information Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / chemical synaptic transmission, postsynaptic / cellular response to ammonium ion / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / neuron spine / myosin V binding ...Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / chemical synaptic transmission, postsynaptic / cellular response to ammonium ion / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / neuron spine / myosin V binding / Trafficking of AMPA receptors / dendritic spine membrane / 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 / AMPA glutamate receptor activity / protein kinase A binding / Trafficking of GluR2-containing AMPA receptors / immunoglobulin binding / 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 / 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 / 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 / cytoskeletal protein binding / ionotropic glutamate receptor signaling pathway / monoatomic ion transmembrane transport / dendrite cytoplasm / 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 / receptor internalization / synaptic vesicle membrane / response to organic cyclic compound / response to peptide hormone / cerebral cortex development / recycling endosome / small GTPase binding / cellular response to growth factor stimulus / recycling endosome membrane / G-protein beta-subunit binding / cell-cell junction / synaptic vesicle / presynapse / response to estradiol / presynaptic membrane / signaling receptor activity / amyloid-beta binding / cell body / growth cone / chemical synaptic transmission / perikaryon Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 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 |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7occ.cif.gz | 298.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7occ.ent.gz | 223.3 KB | Display | PDB format |
PDBx/mmJSON format | 7occ.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/oc/7occ ftp://data.pdbj.org/pub/pdb/validation_reports/oc/7occ | HTTPS FTP |
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-Related structure data
Related structure data | 12803MC 7ocaC 7ocdC 7oceC 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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-Components
#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 / 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 / Production host: Homo sapiens (human) / References: UniProt: P19491 #3: Polysaccharide | Source method: isolated from a genetically manipulated source #4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / 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 heterotertramer in complex with auxiliary subunits TARP gamma 8 and CNIH2 Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
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. |
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 |
Image recording | 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: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 228721 / Symmetry type: POINT | |||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | |||||||||
Atomic model building | PDB-ID: 6QKZ |