+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6whx | |||||||||
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タイトル | GluN1b-GluN2B NMDA receptor in complex with GluN2B antagonist SDZ 220-040, class 2 | |||||||||
要素 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / NMDARs / Ligand-gated ion channels (リガンド依存性イオンチャネル) / METAL TRANSPORT / Ionotropic glutamate receptor / GluN2B antagonist | |||||||||
機能・相同性 | 機能・相同性情報 neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / NMDA selective glutamate receptor signaling pathway / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / 感作 / pons maturation / regulation of cell communication ...neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / NMDA selective glutamate receptor signaling pathway / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / 感作 / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / protein localization to postsynaptic membrane / apical dendrite / 樹状突起 / regulation of respiratory gaseous exchange / propylene metabolic process / response to glycine / response to other organism / fear response / response to methylmercury / voltage-gated monoatomic cation channel activity / positive regulation of cysteine-type endopeptidase activity / response to morphine / glutamate-gated calcium ion channel activity / cellular response to dsRNA / response to carbohydrate / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / negative regulation of dendritic spine maintenance / cellular response to lipid / positive regulation of glutamate secretion / NMDA glutamate receptor activity / response to growth hormone / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / Synaptic adhesion-like molecules / parallel fiber to Purkinje cell synapse / calcium ion transmembrane import into cytosol / response to manganese ion / protein heterotetramerization / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / neuromuscular process / regulation of synapse assembly / 活動電位 / glycine binding / positive regulation of calcium ion transport into cytosol / male mating behavior / regulation of neuronal synaptic plasticity / regulation of dendrite morphogenesis / regulation of axonogenesis / heterocyclic compound binding / receptor clustering / suckling behavior / behavioral response to pain / startle response / response to amine / monoatomic cation transmembrane transport / social behavior / small molecule binding / regulation of MAPK cascade / positive regulation of excitatory postsynaptic potential / ligand-gated monoatomic ion channel activity / response to magnesium ion / 学習 / monoatomic cation transport / excitatory synapse / positive regulation of dendritic spine maintenance / extracellularly glutamate-gated ion channel activity / cellular response to organic cyclic compound / neuron development / Unblocking of NMDA receptors, glutamate binding and activation / long-term memory / glutamate receptor binding / regulation of postsynaptic membrane potential / behavioral fear response / multicellular organismal response to stress / phosphatase binding / D2 dopamine receptor binding / calcium ion homeostasis / synaptic cleft / cellular response to manganese ion / prepulse inhibition / positive regulation of synaptic transmission / detection of mechanical stimulus involved in sensory perception of pain / response to mechanical stimulus / regulation of neuron apoptotic process / response to electrical stimulus / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / monoatomic cation channel activity / cellular response to forskolin / sensory perception of pain 類似検索 - 分子機能 | |||||||||
生物種 | Rattus norvegicus (ドブネズミ) | |||||||||
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: 4.09 Å | |||||||||
データ登録者 | Chou, T. / Tajima, N. / Furukawa, H. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Cell / 年: 2020 タイトル: Structural Basis of Functional Transitions in Mammalian NMDA Receptors. 著者: Tsung-Han Chou / Nami Tajima / Annabel Romero-Hernandez / Hiro Furukawa / 要旨: Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of ...Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of GluN1 and GluN2 subunits, which bind glycine and glutamate, respectively, to activate their ion channels. Despite importance in brain physiology, the precise mechanisms by which activation and inhibition occur via subunit-specific binding of agonists and antagonists remain largely unknown. Here, we show the detailed patterns of conformational changes and inter-subunit and -domain reorientation leading to agonist-gating and subunit-dependent competitive inhibition by providing multiple structures in distinct ligand states at 4 Å or better. The structures reveal that activation and competitive inhibition by both GluN1 and GluN2 antagonists occur by controlling the tension of the linker between the ligand-binding domain and the transmembrane ion channel of the GluN2 subunit. Our results provide detailed mechanistic insights into NMDAR pharmacology, activation, and inhibition, which are fundamental to the brain physiology. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6whx.cif.gz | 524.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6whx.ent.gz | 405.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6whx.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/wh/6whx ftp://data.pdbj.org/pub/pdb/validation_reports/wh/6whx | HTTPS FTP |
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-関連構造データ
関連構造データ | 21679MC 6usuC 6usvC 6whrC 6whsC 6whtC 6whuC 6whvC 6whwC 6whyC 6wi0C 6wi1C M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 108085.633 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P35439*PLUS #2: タンパク質 | 分子量: 98845.859 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q00960*PLUS #3: 糖 | #4: 化合物 | 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: NMDA receptor GluN1b/2B functional ion channel complex タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 85 % / 凍結前の試料温度: 295 K |
-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: FEI TITAN 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 FIELDBright-field microscopy |
撮影 | 電子線照射量: 64.5 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
EMソフトウェア | 名称: cisTEM / バージョン: 1.0.0 / カテゴリ: 3次元再構成 |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
対称性 | 点対称性: C1 (非対称) |
3次元再構成 | 解像度: 4.09 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 109232 / 対称性のタイプ: POINT |