+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-3356 | |||||||||
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タイトル | Activation of NMDA receptors and the mechanism of inhibition by ifenprodil - Class Y | |||||||||
マップデータ | Class Y, unsharpened, unmasked map | |||||||||
試料 |
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キーワード | NMDA receptor (NMDA型グルタミン酸受容体) / glutamate receptor (グルタミン酸受容体) / GluN1 / GluN2B / ion channel (イオンチャネル) | |||||||||
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 / cellular response to dsRNA / glutamate-gated calcium ion channel activity / 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 / regulation of postsynaptic membrane potential / long-term memory / glutamate receptor binding / behavioral fear response / phosphatase binding / D2 dopamine receptor binding / multicellular organismal response to stress / 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 / response to electrical stimulus / regulation of neuron apoptotic process / presynaptic active zone membrane / glutamate-gated receptor activity / 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 | 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_3356.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-3356-v30.xml emd-3356.xml | 11.8 KB 11.8 KB | 表示 表示 | EMDBヘッダ |
画像 | image_3356.png | 408.7 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-3356 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3356 | HTTPS FTP |
-関連構造データ
関連構造データ | 5fxkMC 3352C 3353C 3354C 3355C 5b3jC 5fxgC 5fxhC 5fxiC 5fxjC 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_3356.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 Y, unsharpened, unmasked map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 ReceptorNMDA型グルタミン酸受容体 |
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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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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 FIELDBright-field microscopy / 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 |
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 |
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: 15000 |
-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-5fxk: |