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Yorodumi- PDB-8p3u: Homomeric GluA1 in tandem with TARP gamma-3, desensitized conform... -
+Open data
-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 membrane potential / chemical synaptic transmission, postsynaptic / cellular response to ammonium ion / neurotransmitter receptor transport, postsynaptic endosome to lysosome / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / LGI-ADAM interactions ...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 transport, postsynaptic endosome to lysosome / 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 / channel regulator activity / dendritic spine membrane / postsynaptic neurotransmitter receptor diffusion trapping / response to arsenic-containing substance / cellular response to dsRNA / Synaptic adhesion-like molecules / neurotransmitter receptor localization to postsynaptic specialization membrane / long-term synaptic depression / beta-2 adrenergic receptor binding / protein kinase A binding / cellular response to peptide hormone stimulus / neuronal cell body membrane / spinal cord development / Activation of AMPA receptors / response to lithium ion / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / Trafficking of GluR2-containing AMPA receptors / immunoglobulin binding / AMPA glutamate receptor complex / neuronal action potential / excitatory synapse / ionotropic glutamate receptor complex / adenylate cyclase binding / cellular response to organic cyclic compound / asymmetric synapse / G-protein alpha-subunit binding / protein targeting / regulation of receptor recycling / Unblocking of NMDA receptors, glutamate binding and activation / long-term memory / voltage-gated calcium channel activity / glutamate receptor binding / regulation of postsynaptic membrane potential / positive regulation of synaptic transmission / response to electrical stimulus / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / 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 / monoatomic ion transmembrane transport / positive regulation of synaptic transmission, glutamatergic / dendritic shaft / response to cocaine / 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 / regulation of synaptic plasticity / modulation of chemical synaptic transmission / neuromuscular junction / Schaffer collateral - CA1 synapse / protein localization / receptor internalization / synaptic vesicle membrane / response to organic cyclic compound / cerebral cortex development / response to peptide hormone / response to toxic substance / cellular response to growth factor stimulus / recycling endosome / small GTPase binding / recycling endosome membrane / G-protein beta-subunit binding / cell-cell junction / synaptic vesicle / presynapse / response to estradiol / presynaptic membrane / cell body / amyloid-beta binding / chemical synaptic transmission / postsynaptic membrane / early endosome membrane / postsynapse / scaffold protein binding / dendritic spine 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
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/p3/8p3u ftp://data.pdbj.org/pub/pdb/validation_reports/p3/8p3u | HTTPS FTP |
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-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 FIELDBright-field microscopy / 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 |