+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6usv | |||||||||
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タイトル | Crystal structure of GluN1/GluN2A ligand-binding domain in complex with glycine and SDZ 220-040 | |||||||||
要素 | (Glutamate receptor ionotropic, NMDA ...) x 2 | |||||||||
キーワード | METAL TRANSPORT / NMDARs / LBD / Ion channels | |||||||||
機能・相同性 | 機能・相同性情報 neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / response to environmental enrichment / EPHB-mediated forward signaling ...neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / response to environmental enrichment / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / olfactory learning / serotonin metabolic process / conditioned place preference / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / response to other organism / positive regulation of inhibitory postsynaptic potential / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / cellular response to magnesium ion / response to methylmercury / voltage-gated monoatomic cation channel activity / sleep / cellular response to dsRNA / dendritic spine organization / response to carbohydrate / regulation of monoatomic cation transmembrane transport / cellular response to lipid / locomotion / response to morphine / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / regulation of NMDA receptor activity / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / calcium ion transmembrane import into cytosol / glutamate-gated calcium ion channel activity / glutamate binding / neuromuscular process / cellular response to zinc ion / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / regulation of synapse assembly / action potential / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of dendrite morphogenesis / regulation of axonogenesis / male mating behavior / spinal cord development / dopamine metabolic process / suckling behavior / startle response / response to amine / monoatomic cation transmembrane transport / monoatomic cation transport / regulation of neuronal synaptic plasticity / modulation of excitatory postsynaptic potential / response to lithium ion / associative learning / positive regulation of excitatory postsynaptic potential / social behavior / ligand-gated monoatomic ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / response to light stimulus / positive regulation of protein targeting to membrane / neuron development / Unblocking of NMDA receptors, glutamate binding and activation / regulation of postsynaptic membrane potential / postsynaptic density, intracellular component / phosphatase binding / cellular response to manganese ion / calcium ion homeostasis / glutamate receptor binding / prepulse inhibition / multicellular organismal response to stress / monoatomic cation channel activity / long-term memory / regulation of neuron apoptotic process / synaptic cleft / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / sensory perception of pain / cell adhesion molecule binding / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to amphetamine / ionotropic glutamate receptor signaling pathway / excitatory postsynaptic potential / hippocampal mossy fiber to CA3 synapse 類似検索 - 分子機能 | |||||||||
生物種 | Rattus norvegicus (ドブネズミ) | |||||||||
手法 | X線回折 / シンクロトロン / 分子置換 / 解像度: 2.304 Å | |||||||||
データ登録者 | Romero-Hernandez, A. / Tajima, N. / Chou, T. / 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
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 | 6usv.cif.gz | 129.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6usv.ent.gz | 96 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6usv.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 | 6usv_validation.pdf.gz | 363.6 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6usv_full_validation.pdf.gz | 364.3 KB | 表示 | |
XML形式データ | 6usv_validation.xml.gz | 1.7 KB | 表示 | |
CIF形式データ | 6usv_validation.cif.gz | 7.6 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/us/6usv ftp://data.pdbj.org/pub/pdb/validation_reports/us/6usv | HTTPS FTP |
-関連構造データ
関連構造データ | 6usuC 6whrC 6whsC 6whtC 6whuC 6whvC 6whwC 6whxC 6whyC 6wi0C 6wi1C 4nf8S S: 精密化の開始モデル C: 同じ文献を引用 (文献) |
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類似構造データ |
-リンク
-集合体
登録構造単位 |
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1 |
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単位格子 |
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-要素
-Glutamate receptor ionotropic, NMDA ... , 2種, 2分子 AB
#1: タンパク質 | 分子量: 33340.031 Da / 分子数: 1 / 断片: UNP residues 415-565, 684-821 / 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: Escherichia coli K-12 (大腸菌) / 参照: UniProt: P35439 |
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#2: タンパク質 | 分子量: 31785.299 Da / 分子数: 1 / 断片: UNP residues 402-539, 661-802 / 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: Grin2a / 発現宿主: Escherichia coli K-12 (大腸菌) / 参照: UniProt: Q00959 |
-非ポリマー , 4種, 45分子
#3: 化合物 | ChemComp-GLY / |
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#4: 化合物 | ChemComp-QGP / ( |
#5: 化合物 | ChemComp-GOL / |
#6: 水 | ChemComp-HOH / |
-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: X線回折 / 使用した結晶の数: 1 |
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-試料調製
結晶 | マシュー密度: 2.36 Å3/Da / 溶媒含有率: 47.82 % |
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結晶化 | 温度: 291 K / 手法: 蒸発脱水法 / pH: 7 詳細: 0.2 M HEPES, pH 7.0, 60-90 mM sodium chloride, 15-20% PEG2000 MME |
-データ収集
回折 | 平均測定温度: 100 K / Serial crystal experiment: N |
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放射光源 | 由来: シンクロトロン / サイト: APS / ビームライン: 23-ID-B / 波長: 0.97 Å |
検出器 | タイプ: DECTRIS EIGER X 16M / 検出器: PIXEL / 日付: 2013年11月11日 |
放射 | モノクロメーター: Double crystal cryo-cooled Si(111) プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 波長: 0.97 Å / 相対比: 1 |
反射 | 解像度: 2.3→49.5 Å / Num. obs: 26575 / % possible obs: 95 % / 冗長度: 4.8 % / Biso Wilson estimate: 44.07 Å2 / Rpim(I) all: 0.042 / Rsym value: 0.082 / Net I/σ(I): 9.5 |
反射 シェル | 解像度: 2.3→2.34 Å / Num. unique obs: 1276 / CC1/2: 0.872 / Rpim(I) all: 0.579 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: 分子置換 開始モデル: PDB entry 4NF8 解像度: 2.304→49.497 Å / SU ML: 0.35 / 交差検証法: THROUGHOUT / σ(F): 1.34 / 位相誤差: 28.37
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溶媒の処理 | 減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso max: 86.96 Å2 / Biso mean: 45.8 Å2 / Biso min: 22.81 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: final / 解像度: 2.304→49.497 Å
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拘束条件 |
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LS精密化 シェル | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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