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基本情報
登録情報 | データベース: PDB / ID: 8.0E+96 | |||||||||
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タイトル | Glycine and glutamate bound Human GluN1a-GluN2D NMDA receptor | |||||||||
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![]() | TRANSPORT PROTEIN / Ligand-gated ion channel / ionotropic glutamate receptor / synaptic protein / voltage-gate ion channel | |||||||||
機能・相同性 | ![]() excitatory chemical synaptic transmission / regulation of sensory perception of pain / cellular response to L-glutamate / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity ...excitatory chemical synaptic transmission / regulation of sensory perception of pain / cellular response to L-glutamate / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / Neurexins and neuroligins / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / glycine binding / positive regulation of calcium ion transport into cytosol / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / startle response / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / positive regulation of excitatory postsynaptic potential / Long-term potentiation / ligand-gated monoatomic ion channel activity / excitatory synapse / glutamate-gated calcium ion channel activity / calcium ion homeostasis / synaptic cleft / glutamate-gated receptor activity / presynaptic active zone membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / EPHB-mediated forward signaling / Ras activation upon Ca2+ influx through NMDA receptor / ionotropic glutamate receptor signaling pathway / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic / adult locomotory behavior / excitatory postsynaptic potential / regulation of membrane potential / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / long-term synaptic potentiation / postsynaptic density membrane / visual learning / regulation of synaptic plasticity / brain development / terminal bouton / synaptic vesicle / signaling receptor activity / amyloid-beta binding / RAF/MAP kinase cascade / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / postsynaptic density / calmodulin binding / neuron projection / glutamatergic synapse / dendrite / synapse / calcium ion binding / endoplasmic reticulum membrane / protein-containing complex binding / cell surface / positive regulation of transcription by RNA polymerase II / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
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: 3.38 Å | |||||||||
![]() | Kang, H. / Furukawa, H. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs. 著者: Tsung-Han Chou / Hyunook Kang / Noriko Simorowski / Stephen F Traynelis / Hiro Furukawa / ![]() 要旨: Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. ...Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. NMDARs are glycine- and glutamate-gated ion channels that exist as heterotetramers composed of obligatory GluN1 and GluN2(A-D) and/or GluN3(A-B). The GluN2C and GluN2D subunits form ion channels with distinct properties and spatio-temporal expression patterns. Here, we provide the structures of the agonist-bound human GluN1-2C NMDAR in the presence and absence of the GluN2C-selective positive allosteric potentiator (PAM), PYD-106, the agonist-bound GluN1-2A-2C tri-heteromeric NMDAR, and agonist-bound GluN1-2D NMDARs by single-particle electron cryomicroscopy. Our analysis shows unique inter-subunit and domain arrangements of the GluN2C NMDARs, which contribute to functional regulation and formation of the PAM binding pocket and is distinct from GluN2D NMDARs. Our findings here provide the fundamental blueprint to study GluN2C- and GluN2D-containing NMDARs, which are uniquely involved in neuropsychiatric disorders. | |||||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 499.7 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 919.6 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 955.4 KB | 表示 | |
XML形式データ | ![]() | 77.4 KB | 表示 | |
CIF形式データ | ![]() | 116.1 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 27957MC ![]() 8e92C ![]() 8e93C ![]() 8e94C ![]() 8e97C ![]() 8e98C ![]() 8e99C 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 93078.250 Da / 分子数: 2 / 変異: C22S, R844N, R845G, K846A / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q05586 #2: タンパク質 | 分子量: 96760.492 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: O15399 #3: 化合物 | #4: 糖 | ChemComp-NAG / #5: 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 |
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試料調製
構成要素 | 名称: Hetero-tetrameric GluN1a-GluN2D NMDA receptors / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.5 |
試料 | 濃度: 4 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
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: 285 K |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2400 nm / 最小 デフォーカス(公称値): 600 nm |
試料ホルダ | 凍結剤: NITROGEN |
撮影 | 電子線照射量: 74.7 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 20 eV |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.2_4158: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 8012932 | ||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.38 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 199693 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT | ||||||||||||||||||||||||
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