+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 9b36 | |||||||||||||||
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タイトル | Open state of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to two concanavalin A dimers. Composite map. | |||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / kainate receptor / GluK2 / positive allosteric modulator / BPAM344 / open / concanavalin A / ConA / glutamate | |||||||||||||||
機能・相同性 | 機能・相同性情報 mossy fiber rosette / detection of cold stimulus involved in thermoception / Activation of Na-permeable kainate receptors / kainate selective glutamate receptor complex / Activation of Ca-permeable Kainate Receptor / D-glucose binding / negative regulation of synaptic transmission, glutamatergic / regulation of short-term neuronal synaptic plasticity / inhibitory postsynaptic potential / glutamate receptor activity ...mossy fiber rosette / detection of cold stimulus involved in thermoception / Activation of Na-permeable kainate receptors / kainate selective glutamate receptor complex / Activation of Ca-permeable Kainate Receptor / D-glucose binding / negative regulation of synaptic transmission, glutamatergic / regulation of short-term neuronal synaptic plasticity / inhibitory postsynaptic potential / glutamate receptor activity / ubiquitin conjugating enzyme binding / receptor clustering / modulation of excitatory postsynaptic potential / extracellularly glutamate-gated ion channel activity / D-mannose binding / regulation of JNK cascade / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / behavioral fear response / neuronal action potential / positive regulation of synaptic transmission / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / presynaptic modulation of chemical synaptic transmission / dendrite cytoplasm / hippocampal mossy fiber to CA3 synapse / regulation of membrane potential / SNARE binding / excitatory postsynaptic potential / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / modulation of chemical synaptic transmission / terminal bouton / intracellular calcium ion homeostasis / vasodilation / positive regulation of neuron apoptotic process / manganese ion binding / presynaptic membrane / scaffold protein binding / chemical synaptic transmission / perikaryon / postsynaptic membrane / neuron apoptotic process / negative regulation of neuron apoptotic process / postsynaptic density / axon / neuronal cell body / glutamatergic synapse / dendrite / ubiquitin protein ligase binding / calcium ion binding / synapse / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 | |||||||||||||||
生物種 | Rattus norvegicus (ドブネズミ) Canavalia ensiformis (タチナタマメ) | |||||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.29 Å | |||||||||||||||
データ登録者 | Nadezhdin, K.D. / Gangwar, S.P. / Sobolevsky, A.I. | |||||||||||||||
資金援助 | 米国, 4件
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引用 | ジャーナル: Nature / 年: 2024 タイトル: Kainate receptor channel opening and gating mechanism. 著者: Shanti Pal Gangwar / Maria V Yelshanskaya / Kirill D Nadezhdin / Laura Y Yen / Thomas P Newton / Muhammed Aktolun / Maria G Kurnikova / Alexander I Sobolevsky / 要旨: Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and ...Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and synaptic plasticity during the development and function of the central nervous system and are implicated in various neurological and psychiatric diseases, including epilepsy, depression, schizophrenia, anxiety and autism. Although structures of kainate receptor domains and subunit assemblies are available, the mechanism of kainate receptor gating remains poorly understood. Here we present cryo-electron microscopy structures of the kainate receptor GluK2 in the presence of the agonist glutamate and the positive allosteric modulators lectin concanavalin A and BPAM344. Concanavalin A and BPAM344 inhibit kainate receptor desensitization and prolong activation by acting as a spacer between the amino-terminal and ligand-binding domains and a stabilizer of the ligand-binding domain dimer interface, respectively. Channel opening involves the kinking of all four pore-forming M3 helices. Our structures reveal the molecular basis of kainate receptor gating, which could guide the development of drugs for treatment of neurological disorders. | |||||||||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 9b36.cif.gz | 799.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb9b36.ent.gz | 669.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 9b36.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 9b36_validation.pdf.gz | 3.5 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 9b36_full_validation.pdf.gz | 3.6 MB | 表示 | |
XML形式データ | 9b36_validation.xml.gz | 125.5 KB | 表示 | |
CIF形式データ | 9b36_validation.cif.gz | 182.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/b3/9b36 ftp://data.pdbj.org/pub/pdb/validation_reports/b3/9b36 | HTTPS FTP |
-関連構造データ
関連構造データ | 44129MC 9b33C 9b34C 9b35C 9b37C 9b38C 9b39C C: 同じ文献を引用 (文献) M: このデータのモデリングに利用したマップデータ |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-タンパク質 , 2種, 8分子 ABCDEFGH
#1: タンパク質 | 分子量: 102976.586 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 遺伝子: Grik2, Glur6 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P42260 #2: タンパク質 | 分子量: 25622.385 Da / 分子数: 4 / 由来タイプ: 天然 / 由来: (天然) Canavalia ensiformis (タチナタマメ) / 参照: UniProt: C0HJY1 |
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-糖 , 7種, 28分子
#3: 多糖 | #4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 多糖 | beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose- ...beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #6: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #7: 多糖 | #8: 多糖 | #9: 多糖 | |
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-非ポリマー , 6種, 38分子
#10: 化合物 | ChemComp-2J9 / #11: 化合物 | ChemComp-GLU / #12: 化合物 | ChemComp-POV / ( #13: 化合物 | ChemComp-CLR / #14: 化合物 | ChemComp-ZN / #15: 化合物 | ChemComp-CA / |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: full-length rat GluK2 tetramer in complex with two concanavalin A dimers タイプ: COMPLEX / Entity ID: #1-#2 / 由来: MULTIPLE SOURCES | ||||||||||||||||||||||||||||||||||||||||
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分子量 | 値: 0.51 MDa / 実験値: NO | ||||||||||||||||||||||||||||||||||||||||
由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) | ||||||||||||||||||||||||||||||||||||||||
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: Human embryonic kidney 293 / プラスミド: pEG BacMam | ||||||||||||||||||||||||||||||||||||||||
緩衝液 | pH: 8 | ||||||||||||||||||||||||||||||||||||||||
緩衝液成分 |
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試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのタイプ: UltrAuFoil R1.2/1.3 | ||||||||||||||||||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: TFS KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 1000 nm / Cs: 2.7 mm |
撮影 | 平均露光時間: 2.5 sec. / 電子線照射量: 58 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 5 / 実像数: 22990 |
画像スキャン | 横: 5760 / 縦: 4092 |
-解析
EMソフトウェア |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 8660229 | ||||||||||||||||||||||||||||
対称性 | 点対称性: C2 (2回回転対称) | ||||||||||||||||||||||||||||
3次元再構成 | 解像度: 4.29 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 109827 詳細: This is composite map. Reference map: 4.29 A ATD: 3.5 A LBD-TMD: 3.4 A ConA: 3.58 A 対称性のタイプ: POINT | ||||||||||||||||||||||||||||
原子モデル構築 | 空間: REAL | ||||||||||||||||||||||||||||
拘束条件 |
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