+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-3355 | |||||||||
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タイトル | Activation of NMDA receptors and the mechanism of inhibition by ifenprodil - Class X | |||||||||
マップデータ | Class X, unsharpened, unmasked map | |||||||||
試料 |
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キーワード | NMDA receptor / glutamate receptor / GluN1 / GluN2B / ion channel | |||||||||
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 / sensitization / 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 / sensitization / 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 / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / dendritic branch / response to other organism / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / 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 / positive regulation of cysteine-type endopeptidase activity / voltage-gated monoatomic cation channel activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / cellular response to lipid / NMDA glutamate receptor activity / response to morphine / positive regulation of glutamate secretion / response to growth hormone / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / NMDA selective glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / regulation of synapse assembly / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of axonogenesis / regulation of dendrite morphogenesis / male mating behavior / heterocyclic compound binding / receptor clustering / suckling behavior / startle response / behavioral response to pain / response to amine / small molecule binding / regulation of neuronal synaptic plasticity / action potential / monoatomic cation transmembrane transport / monoatomic cation transport / associative learning / positive regulation of excitatory postsynaptic potential / regulation of MAPK cascade / response to magnesium ion / social behavior / ligand-gated monoatomic ion channel activity / cellular response to organic cyclic compound / excitatory synapse / extracellularly glutamate-gated ion channel activity / cellular response to glycine / positive regulation of dendritic spine maintenance / behavioral fear response / neuron development / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / postsynaptic density, intracellular component / cellular response to manganese ion / glutamate receptor binding / multicellular organismal response to stress / D2 dopamine receptor binding / long-term memory / positive regulation of synaptic transmission, glutamatergic / monoatomic cation channel activity / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain / calcium ion homeostasis / regulation of neuron apoptotic process / synaptic cleft / response to electrical stimulus / response to mechanical stimulus / glutamate-gated receptor activity 類似検索 - 分子機能 | |||||||||
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: 6.25 Å | |||||||||
データ登録者 | Tajima N / Karakas E / Grant T / Simorowski N / Diaz-Avalos R / Grigorieff N / Furukawa H | |||||||||
引用 | ジャーナル: Nature / 年: 2016 タイトル: Activation of NMDA receptors and the mechanism of inhibition by ifenprodil. 著者: Nami Tajima / Erkan Karakas / Timothy Grant / Noriko Simorowski / Ruben Diaz-Avalos / Nikolaus Grigorieff / Hiro Furukawa / 要旨: The physiology of N-methyl-d-aspartate (NMDA) receptors is fundamental to brain development and function. NMDA receptors are ionotropic glutamate receptors that function as heterotetramers composed ...The physiology of N-methyl-d-aspartate (NMDA) receptors is fundamental to brain development and function. NMDA receptors are ionotropic glutamate receptors that function as heterotetramers composed mainly of GluN1 and GluN2 subunits. Activation of NMDA receptors requires binding of neurotransmitter agonists to a ligand-binding domain (LBD) and structural rearrangement of an amino-terminal domain (ATD). Recent crystal structures of GluN1-GluN2B NMDA receptors bound to agonists and an allosteric inhibitor, ifenprodil, represent the allosterically inhibited state. However, how the ATD and LBD move to activate the NMDA receptor ion channel remains unclear. Here we applied X-ray crystallography, single-particle electron cryomicroscopy and electrophysiology to rat NMDA receptors to show that, in the absence of ifenprodil, the bi-lobed structure of GluN2 ATD adopts an open conformation accompanied by rearrangement of the GluN1-GluN2 ATD heterodimeric interface, altering subunit orientation in the ATD and LBD and forming an active receptor conformation that gates the ion channel. | |||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_3355.map.gz | 19.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-3355-v30.xml emd-3355.xml | 11.8 KB 11.8 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_3355.png | 434.4 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-3355 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3355 | HTTPS FTP |
-関連構造データ
関連構造データ | 5fxjMC 3352C 3353C 3354C 3356C 5b3jC 5fxgC 5fxhC 5fxiC 5fxkC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_3355.map.gz / 形式: CCP4 / 大きさ: 62.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Class X, unsharpened, unmasked map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.31 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : NMDA Receptor
全体 | 名称: NMDA Receptor |
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要素 |
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-超分子 #1000: NMDA Receptor
超分子 | 名称: NMDA Receptor / タイプ: sample / ID: 1000 詳細: The sample was purified in the presence of agonists Glycine and L-glutamate. 集合状態: One heterotetramer of 2 GluN1 and 2 GluN2B subunits Number unique components: 2 |
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分子量 | 理論値: 370 KDa |
-分子 #1: N-methyl-D-aspartate receptor GluN1
分子 | 名称: N-methyl-D-aspartate receptor GluN1 / タイプ: protein_or_peptide / ID: 1 / Name.synonym: GluN1, NR1 / コピー数: 2 / 集合状態: dimer / 組換発現: Yes |
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由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) / 別称: Rat / 細胞中の位置: Plasma membane |
分子量 | 理論値: 93 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) 組換株: Sf9 CRL-1711 / 組換細胞: Sf9 / 組換プラスミド: Modified pFL and pUCDM |
配列 | UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-分子 #2: N-methyl-D-aspartate receptor GluN2B
分子 | 名称: N-methyl-D-aspartate receptor GluN2B / タイプ: protein_or_peptide / ID: 2 / Name.synonym: GluN2B, NR2B / コピー数: 2 / 集合状態: Dimer / 組換発現: Yes |
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由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) / 別称: Rat / 細胞中の位置: Plasma membane |
分子量 | 理論値: 92 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) 組換株: Sf9 CRL-1711 / 組換細胞: Sf9 / 組換プラスミド: Modified pFL and pUCDM |
配列 | UniProtKB: Glutamate receptor ionotropic, NMDA 2B |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 2 mg/mL |
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緩衝液 | pH: 7 詳細: 200 mM NaCl, 20 mM HEPES pH 7.0, 10 mM Glycine, 10 mM L-Glutamate, 0.002% MNG-3 |
グリッド | 詳細: C-flat 1.2/1.3 Cu 400 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 90 % / 装置: FEI VITROBOT MARK II / 手法: 3s Blot time |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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アライメント法 | Legacy - Electron beam tilt params: 0 |
詳細 | 21s exposure into 70 frames, with an exposure rate of ~8 electrons/pixel/s on the camera. |
日付 | 2015年8月10日 |
撮影 | カテゴリ: CCD フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 実像数: 1200 / 平均電子線量: 100 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 倍率(補正後): 38168 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm / 倍率(公称値): 22500 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
CTF補正 | 詳細: Each Particle |
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最終 再構成 | 想定した対称性 - 点群: C2 (2回回転対称) / アルゴリズム: OTHER / 解像度のタイプ: BY AUTHOR / 解像度: 6.25 Å / 解像度の算出法: OTHER / ソフトウェア - 名称: Unblur, CTFFIND4, FREALIGN 詳細: The highest resolution included in the refinement was 8A. 使用した粒子像数: 14000 |
-原子モデル構築 1
初期モデル | PDB ID: Chain - #0 - Chain ID: A / Chain - #1 - Chain ID: B / Chain - #2 - Chain ID: C / Chain - #3 - Chain ID: D |
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ソフトウェア | 名称: Coot |
詳細 | The individual domains were initially fitted using coot and real space refinement was performed using Phenix |
精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT / 当てはまり具合の基準: Real Space |
得られたモデル | PDB-5fxj: |