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Yorodumi- PDB-8p3u: Homomeric GluA1 in tandem with TARP gamma-3, desensitized conform... -
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-Basic information
Entry | Database: PDB / ID: 8p3u | ||||||||||||
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Title | Homomeric GluA1 in tandem with TARP gamma-3, desensitized conformation 2 | ||||||||||||
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 locomotion involved in locomotory behavior / positive regulation of membrane potential / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / cellular response to ammonium ion / proximal dendrite / neurotransmitter receptor transport, postsynaptic endosome to lysosome ...Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of locomotion involved in locomotory behavior / positive regulation of membrane potential / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / cellular response to ammonium ion / proximal dendrite / neurotransmitter receptor transport, postsynaptic endosome to lysosome / response to sucrose / LGI-ADAM interactions / myosin V binding / Trafficking of AMPA receptors / neuron spine / cellular response to dsRNA / cellular response to L-glutamate / regulation of AMPA receptor activity / conditioned place preference / neurotransmitter receptor internalization / response to arsenic-containing substance / postsynaptic neurotransmitter receptor diffusion trapping / regulation of monoatomic ion transmembrane transport / dendritic spine membrane / Synaptic adhesion-like molecules / long-term synaptic depression / response to morphine / cellular response to peptide hormone stimulus / beta-2 adrenergic receptor binding / neurotransmitter receptor localization to postsynaptic specialization membrane / protein kinase A binding / peptide hormone receptor binding / response to psychosocial stress / spinal cord development / neuronal cell body membrane / Activation of AMPA receptors / behavioral response to pain / perisynaptic space / AMPA glutamate receptor activity / transmission of nerve impulse / channel regulator activity / cellular response to organic cyclic compound / response to lithium ion / Trafficking of GluR2-containing AMPA receptors / immunoglobulin binding / AMPA glutamate receptor complex / excitatory synapse / adenylate cyclase binding / positive regulation of excitatory postsynaptic potential / ionotropic glutamate receptor complex / regulation of postsynaptic membrane potential / postsynaptic density, intracellular component / asymmetric synapse / neuronal action potential / regulation of receptor recycling / G-protein alpha-subunit binding / Unblocking of NMDA receptors, glutamate binding and activation / voltage-gated calcium channel activity / glutamate receptor binding / protein targeting / positive regulation of synaptic transmission / response to electrical stimulus / long-term memory / glutamate-gated receptor activity / response to fungicide / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / ionotropic glutamate receptor binding / somatodendritic compartment / dendrite membrane / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of synaptic transmission, glutamatergic / response to nutrient levels / dendritic shaft / response to cocaine / synaptic membrane / synaptic transmission, glutamatergic / long-term synaptic potentiation / cellular response to amino acid stimulus / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / postsynaptic density membrane / modulation of chemical synaptic transmission / neuromuscular junction / response to organic cyclic compound / Schaffer collateral - CA1 synapse / regulation of synaptic plasticity / cellular response to growth factor stimulus / receptor internalization / recycling endosome / cerebral cortex development / response to peptide hormone / small GTPase binding / response to toxic substance / synaptic vesicle membrane / recycling endosome membrane / G-protein beta-subunit binding / cell-cell junction Similarity search - Function | ||||||||||||
Biological species | Rattus norvegicus (Norway rat) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.77 Å | ||||||||||||
Authors | Zhang, D. / Krieger, J.M. / Greger, I.H. | ||||||||||||
Funding support | United Kingdom, European Union, 3items
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Citation | Journal: Nature / Year: 2023 Title: Structural mobility tunes signalling of the GluA1 AMPA glutamate receptor. Authors: Danyang Zhang / Josip Ivica / James M Krieger / Hinze Ho / Keitaro Yamashita / Imogen Stockwell / Rozbeh Baradaran / Ondrej Cais / Ingo H Greger / Abstract: AMPA glutamate receptors (AMPARs), the primary mediators of excitatory neurotransmission in the brain, are either GluA2 subunit-containing and thus Ca-impermeable, or GluA2-lacking and Ca-permeable. ...AMPA glutamate receptors (AMPARs), the primary mediators of excitatory neurotransmission in the brain, are either GluA2 subunit-containing and thus Ca-impermeable, or GluA2-lacking and Ca-permeable. Despite their prominent expression throughout interneurons and glia, their role in long-term potentiation and their involvement in a range of neuropathologies, structural information for GluA2-lacking receptors is currently absent. Here we determine and characterize cryo-electron microscopy structures of the GluA1 homotetramer, fully occupied with TARPγ3 auxiliary subunits (GluA1/γ3). The gating core of both resting and open-state GluA1/γ3 closely resembles GluA2-containing receptors. However, the sequence-diverse N-terminal domains (NTDs) give rise to a highly mobile assembly, enabling domain swapping and subunit re-alignments in the ligand-binding domain tier that are pronounced in desensitized states. These transitions underlie the unique kinetic properties of GluA1. A GluA2 mutant (F231A) increasing NTD dynamics phenocopies this behaviour, and exhibits reduced synaptic responses, reflecting the anchoring function of the AMPAR NTD at the synapse. Together, this work underscores how the subunit-diverse NTDs determine subunit arrangement, gating properties and ultimately synaptic signalling efficiency among AMPAR subtypes. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8p3u.cif.gz | 445.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8p3u.ent.gz | 335.8 KB | Display | PDB format |
PDBx/mmJSON format | 8p3u.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8p3u_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8p3u_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 8p3u_validation.xml.gz | 72.7 KB | Display | |
Data in CIF | 8p3u_validation.cif.gz | 109.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/p3/8p3u ftp://data.pdbj.org/pub/pdb/validation_reports/p3/8p3u | HTTPS FTP |
-Related structure data
Related structure data | 17395MC 8c1pC 8c1qC 8c1rC 8c1sC 8c2hC 8c2iC 8p3qC 8p3sC 8p3tC 8p3vC 8p3wC 8p3xC 8p3yC 8p3zC 8pivC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 102661.930 Da / Num. of mol.: 4 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: 35435.332 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Cacng3 / Production host: Homo sapiens (human) / References: UniProt: Q8VHX0 |
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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: Homomeric GluA1 AMPA receptor in tandem with TARP gamma 3, plus 1mM quisqualate Type: COMPLEX / Entity ID: all / 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: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1400 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.77 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 59427 / Symmetry type: POINT |