登録情報 データベース : EMDB / ID : EMD-13973 構造の表示 ダウンロードとリンクタイトル Desensitized state of GluA1/2 AMPA receptor in complex with TARP-gamma 8 (TMD) マップデータPostprocessed map obtained after focused refinement of the TMD region of the complex GluA1/2/TARP8 in the desensitised state 詳細 試料複合体 : Complex between GluA1/2 AMPA receptor and auxiliary subunit TARP gamma8タンパク質・ペプチド : AMPA Glutamate Receptor 1, FLIP isoformタンパク質・ペプチド : AMPA Glutamate receptor 2, flip isoform, Q/R editedタンパク質・ペプチド : TARP gamma 8 詳細 キーワード glutamate / AMPA receptor / TARPs / MEMBRANE PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
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 / cellular response to ammonium ion / neurotransmitter receptor transport, postsynaptic endosome to lysosome / L-type voltage-gated calcium channel complex ... 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 / 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 / myosin V binding / Trafficking of AMPA receptors / neuron spine / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / protein phosphatase 2B binding / response to arsenic-containing substance / cellular response to dsRNA / postsynaptic neurotransmitter receptor diffusion trapping / dendritic spine membrane / Synaptic adhesion-like molecules / glutamate-gated calcium ion channel activity / long-term synaptic depression / cellular response to peptide hormone stimulus / protein kinase A binding / spine synapse / spinal cord development / neuronal cell body membrane / dendritic spine neck / dendritic spine head / Activation of AMPA receptors / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / regulation of postsynaptic membrane neurotransmitter receptor levels / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / immunoglobulin binding / AMPA glutamate receptor complex / kainate selective glutamate receptor activity / cellular response to organic cyclic compound / adenylate cyclase binding / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / cellular response to glycine / excitatory synapse / calcium channel regulator activity / asymmetric synapse / regulation of receptor recycling / G-protein alpha-subunit binding / voltage-gated calcium channel activity / Unblocking of NMDA receptors, glutamate binding and activation / neuronal action potential / regulation of postsynaptic membrane potential / postsynaptic density, intracellular component / glutamate receptor binding / positive regulation of synaptic transmission / long-term memory / response to electrical stimulus / glutamate-gated receptor activity / presynaptic active zone membrane / beta-2 adrenergic receptor binding / response to fungicide / regulation of synaptic transmission, glutamatergic / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / dendrite membrane / synapse assembly / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / cytoskeletal protein binding / ionotropic glutamate receptor signaling pathway / dendrite cytoplasm / positive regulation of synaptic transmission, glutamatergic / SNARE binding / response to cocaine / dendritic shaft / 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 / protein tetramerization / cellular response to amino acid stimulus / postsynaptic density membrane / ionotropic glutamate receptor binding / Schaffer collateral - CA1 synapse / modulation of chemical synaptic transmission / establishment of protein localization / regulation of synaptic plasticity / neuromuscular junction / response to organic cyclic compound / terminal bouton / receptor internalization / recycling endosome / response to toxic substance / cerebral cortex development / cellular response to growth factor stimulus 類似検索 - 分子機能 Voltage-dependent calcium channel, gamma-8 subunit / 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 ... Voltage-dependent calcium channel, gamma-8 subunit / 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 類似検索 - ドメイン・相同性 Glutamate receptor 1 / Glutamate receptor 2 / Voltage-dependent calcium channel gamma-8 subunit 類似検索 - 構成要素生物種 Rattus norvegicus (ドブネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.4 Å 詳細 データ登録者Herguedas B / Kohegyi B / Dohrke JN / Watson JF / Zhang D / Ho H / Shaikh SH / Lape R / Krieger JM / Greger IH 資金援助 英国, 3件 詳細 詳細を隠すOrganization Grant number 国 Medical Research Council (MRC, United Kingdom) MC_U105174197 英国 Biotechnology and Biological Sciences Research Council (BBSRC) BB/N002113/1 英国 Spanish Ministry of Science, Innovation, and Universities PID2019-106284GA-I00 英国
引用ジャーナル : Nat Commun / 年 : 2022タイトル : Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor.著者 : Beatriz Herguedas / Bianka K Kohegyi / Jan-Niklas Dohrke / Jake F Watson / Danyang Zhang / Hinze Ho / Saher A Shaikh / Remigijus Lape / James M Krieger / Ingo H Greger / 要旨 : AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory synapses in the brain. Glutamate binding to the receptor's ligand-binding domains (LBDs) leads to ion channel ... AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory synapses in the brain. Glutamate binding to the receptor's ligand-binding domains (LBDs) leads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission and are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs) through currently incompletely resolved mechanisms. Here, electron cryo-microscopy structures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states (at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop ('β1'), elucidating how this TARP stabilizes specific gating states. We further show how TARPs alter channel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we reveal that the Q/R-editing site couples the channel constriction at the filter entrance to the gate, and forms the major cation binding site in the conduction path. Our results provide a mechanistic framework of how TARPs modulate AMPAR gating and conductance. 履歴 登録 2021年12月12日 - ヘッダ(付随情報) 公開 2022年2月23日 - マップ公開 2022年2月23日 - 更新 2023年12月13日 - 現状 2023年12月13日 処理サイト : PDBe / 状態 : 公開
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