Entry Database : PDB / ID : 8c1p Structure visualization Downloads & linksTitle Active state homomeric GluA1 AMPA receptor in complex with TARP gamma 3 ComponentsGlutamate receptor 1 flip isoform Voltage-dependent calcium channel gamma-3 subunit DetailsKeywords MEMBRANE PROTEIN / AMPAR / ion channels / neurotransmissionFunction / homology Function and homology informationFunction Domain/homology Component
Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / 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 / myosin V binding ... Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / 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 / myosin V binding / neuron spine / Trafficking of AMPA receptors / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / response to arsenic-containing substance / cellular response to dsRNA / dendritic spine membrane / postsynaptic neurotransmitter receptor diffusion trapping / Synaptic adhesion-like molecules / glutamate-gated calcium ion channel activity / neurotransmitter receptor localization to postsynaptic specialization membrane / long-term synaptic depression / cellular response to peptide hormone stimulus / beta-2 adrenergic receptor binding / protein kinase A binding / neuronal cell body membrane / spinal cord development / Activation of AMPA receptors / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / immunoglobulin binding / AMPA glutamate receptor complex / adenylate cyclase binding / excitatory synapse / cellular response to organic cyclic compound / ionotropic glutamate receptor complex / asymmetric synapse / G-protein alpha-subunit binding / regulation of receptor recycling / neuronal action potential / voltage-gated calcium channel activity / Unblocking of NMDA receptors, glutamate binding and activation / regulation of postsynaptic membrane potential / glutamate receptor binding / postsynaptic density, intracellular component / protein targeting / positive regulation of synaptic transmission / long-term memory / response to electrical stimulus / presynaptic active zone membrane / glutamate-gated receptor activity / response to fungicide / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / synapse assembly / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / ionotropic glutamate receptor binding / positive regulation of synaptic transmission, glutamatergic / dendritic shaft / response to cocaine / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / long-term synaptic potentiation / cellular response to amino acid stimulus / postsynaptic density membrane / Schaffer collateral - CA1 synapse / regulation of synaptic plasticity / modulation of chemical synaptic transmission / neuromuscular junction / protein localization / receptor internalization / response to organic cyclic compound / recycling endosome / response to toxic substance / cerebral cortex development / synaptic vesicle membrane / cellular response to growth factor stimulus / small GTPase binding / response to peptide hormone / recycling endosome membrane / G-protein beta-subunit binding / cell-cell junction / synaptic vesicle / presynapse / response to estradiol / presynaptic membrane / amyloid-beta binding / cell body / early endosome membrane / scaffold protein binding / postsynapse / chemical synaptic transmission / postsynaptic membrane Similarity search - Function PMP-22/EMP/MP20/Claudin family / Voltage-dependent calcium channel, gamma subunit / PMP-22/EMP/MP20/Claudin superfamily / Bacterial extracellular solute-binding proteins, family 3 / Solute-binding protein family 3/N-terminal domain of MltF / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / : / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain ... PMP-22/EMP/MP20/Claudin family / Voltage-dependent calcium channel, gamma subunit / PMP-22/EMP/MP20/Claudin superfamily / Bacterial extracellular solute-binding proteins, family 3 / Solute-binding protein family 3/N-terminal domain of MltF / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / : / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I Similarity search - Domain/homology CYCLOTHIAZIDE / GLUTAMIC ACID / (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate / PALMITIC ACID / Chem-POV / Glutamate receptor 1 / Voltage-dependent calcium channel gamma-3 subunit Similarity search - ComponentBiological species Rattus norvegicus (Norway rat)Method ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution : 2.9 Å DetailsAuthors Zhang, D. / Ivica, J. / Krieger, J.M. / Ho, H. / Yamashita, K. / Cais, O. / Greger, I. Funding support United Kingdom, 2items Details Hide detailsOrganization Grant number Country Wellcome Trust 223194/Z/21/Z United Kingdom Medical Research Council (MRC, United Kingdom) MC_U105174197 United Kingdom
CitationJournal : Nature / Year : 2023Title : 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 Deposition Dec 21, 2022 Deposition site : PDBE / Processing site : PDBERevision 1.0 Aug 30, 2023 Provider : repository / Type : Initial releaseRevision 1.1 Sep 13, 2023 Group : Database references / Category : citation / citation_authorItem : _citation.country / _citation.journal_abbrev ... _citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.title / _citation.year Revision 1.2 Sep 20, 2023 Group : Database references / Category : citation / citation_authorItem : _citation.pdbx_database_id_PubMed / _citation.title ... _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _citation_author.name Revision 1.3 Oct 11, 2023 Group : Database references / Category : citation / citation_authorItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
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