+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6whs | |||||||||
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タイトル | GluN1b-GluN2B NMDA receptor in non-active 1 conformation at 3.95 angstrom resolution | |||||||||
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 | |||||||||
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 / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / 感作 / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration ...neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / 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 / response to hydrogen sulfide / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / 樹状突起 / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / response to other organism / positive regulation of inhibitory postsynaptic potential / apical dendrite / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / fear response / response to methylmercury / voltage-gated monoatomic cation channel activity / positive regulation of cysteine-type endopeptidase activity / cellular response to dsRNA / response to morphine / response to carbohydrate / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / cellular response to lipid / positive regulation of glutamate secretion / response to growth hormone / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / NMDA selective glutamate receptor complex / glutamate-gated calcium ion channel activity / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor signaling pathway / response to manganese ion / calcium ion transmembrane import into cytosol / 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 / regulation of dendrite morphogenesis / male mating behavior / regulation of axonogenesis / heterocyclic compound binding / suckling behavior / startle response / behavioral response to pain / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / response to amine / receptor clustering / regulation of MAPK cascade / social behavior / 学習 / response to magnesium ion / positive regulation of excitatory postsynaptic potential / monoatomic cation transport / ligand-gated monoatomic ion channel activity / excitatory synapse / cellular response to organic cyclic compound / extracellularly glutamate-gated ion channel activity / cellular response to glycine / small molecule binding / positive regulation of dendritic spine maintenance / Unblocking of NMDA receptors, glutamate binding and activation / neuron development / regulation of postsynaptic membrane potential / behavioral fear response / phosphatase binding / glutamate receptor binding / postsynaptic density, intracellular component / calcium ion homeostasis / cellular response to manganese ion / D2 dopamine receptor binding / prepulse inhibition / multicellular organismal response to stress / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / monoatomic cation channel activity / regulation of neuron apoptotic process / response to electrical stimulus / presynaptic active zone membrane / synaptic cleft / glutamate-gated receptor activity 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 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 | 6whs.cif.gz | 526.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6whs.ent.gz | 408.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6whs.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/6whs ftp://data.pdbj.org/pub/pdb/validation_reports/wh/6whs | HTTPS FTP |
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-関連構造データ
関連構造データ | 21674MC 6usuC 6usvC 6whrC 6whtC 6whuC 6whvC 6whwC 6whxC 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) / 遺伝子: Grin1, Nmdar1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P35439 #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) / 遺伝子: Grin2b 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q00960 #3: 多糖 | #4: 糖 | ChemComp-NAG / 研究の焦点であるリガンドがあるか | N | |
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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: 最終オイラー角割当 |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
対称性 | 点対称性: C2 (2回回転対称) |
3次元再構成 | 解像度: 4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 105348 / 対称性のタイプ: POINT |