+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6mmx | |||||||||
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タイトル | Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* in the 'Extended' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4 | |||||||||
要素 |
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キーワード | TRANSPORT PROTEIN (運搬体タンパク質) / Ligand-gated Ion Channel (リガンド依存性イオンチャネル) / NMDA Receptor (NMDA型グルタミン酸受容体) / ionotropic Glutamate Receptors / membrane protein (膜タンパク質) | |||||||||
機能・相同性 | 機能・相同性情報 response to ammonium ion / directional locomotion / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / serotonin metabolic process / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion ...response to ammonium ion / directional locomotion / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / serotonin metabolic process / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / protein localization to postsynaptic membrane / 樹状突起 / regulation of respiratory gaseous exchange / propylene metabolic process / response to glycine / response to other organism / 睡眠 / cellular response to magnesium ion / response to methylmercury / voltage-gated monoatomic cation channel activity / locomotion / response to morphine / glutamate-gated calcium ion channel activity / cellular response to dsRNA / response to carbohydrate / dendritic spine organization / regulation of monoatomic cation transmembrane transport / cellular response to lipid / NMDA glutamate receptor activity / 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 / cellular response to zinc ion / 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 / dopamine metabolic process / regulation of axonogenesis / spinal cord development / suckling behavior / startle response / response to amine / monoatomic cation transmembrane transport / regulation of NMDA receptor activity / social behavior / positive regulation of excitatory postsynaptic potential / ligand-gated monoatomic ion channel activity / 学習 / monoatomic cation transport / excitatory synapse / response to light stimulus / positive regulation of dendritic spine maintenance / neuron development / Unblocking of NMDA receptors, glutamate binding and activation / long-term memory / glutamate receptor binding / regulation of postsynaptic membrane potential / phosphatase binding / calcium ion homeostasis / synaptic cleft / cellular response to manganese ion / prepulse inhibition / regulation of neuron apoptotic process / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / monoatomic cation channel activity / sensory perception of pain / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to amphetamine / excitatory postsynaptic potential / hippocampal mossy fiber to CA3 synapse / ionotropic glutamate receptor signaling pathway / regulation of membrane potential / cell adhesion molecule binding / 神経発生 / positive regulation of synaptic transmission, glutamatergic / adult locomotory behavior / response to cocaine / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / 学習 / synaptic transmission, glutamatergic / long-term synaptic potentiation / hippocampus development / cellular response to amino acid stimulus / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity 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: 6.99 Å | |||||||||
データ登録者 | Jalali-Yazdi, F. / Chowdhury, S. / Yoshioka, C. / Gouaux, E. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Cell / 年: 2018 タイトル: Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor. 著者: Farzad Jalali-Yazdi / Sandipan Chowdhury / Craig Yoshioka / Eric Gouaux / 要旨: N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory formation, neuronal plasticity, and brain development, with their dysfunction linked to a range of disorders from ischemia to ...N-methyl-D-aspartate receptors (NMDARs) play essential roles in memory formation, neuronal plasticity, and brain development, with their dysfunction linked to a range of disorders from ischemia to schizophrenia. Zinc and pH are physiological allosteric modulators of NMDARs, with GluN2A-containing receptors inhibited by nanomolar concentrations of divalent zinc and by excursions to low pH. Despite the widespread importance of zinc and proton modulation of NMDARs, the molecular mechanism by which these ions modulate receptor activity has proven elusive. Here, we use cryoelectron microscopy to elucidate the structure of the GluN1/GluN2A NMDAR in a large ensemble of conformations under a range of physiologically relevant zinc and proton concentrations. We show how zinc binding to the amino terminal domain elicits structural changes that are transduced though the ligand-binding domain and result in constriction of the ion channel gate. | |||||||||
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 | 6mmx.cif.gz | 547.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6mmx.ent.gz | 458.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6mmx.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/mm/6mmx ftp://data.pdbj.org/pub/pdb/validation_reports/mm/6mmx | HTTPS FTP |
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-関連構造データ
関連構造データ | 9165MC 9147C 9148C 9149C 9150C 9151C 9152C 9153C 9154C 9155C 9156C 9157C 9158C 9159C 9160C 9161C 9162C 9163C 9164C 6mm9C 6mmaC 6mmbC 6mmgC 6mmhC 6mmiC 6mmjC 6mmkC 6mmlC 6mmmC 6mmnC 6mmpC 6mmrC 6mmsC 6mmtC 6mmuC 6mmvC 6mmwC 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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-要素
#1: タンパク質 | 分子量: 94189.781 Da / 分子数: 2 / 断片: UNP residues 1-838 / 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 / 細胞株 (発現宿主): TSA-201 / 器官 (発現宿主): Kidney / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P35439 #2: タンパク質 | 分子量: 93630.258 Da / 分子数: 2 / 断片: UNP residues 1-837 / Mutation: H128S, N687Q / 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 / 細胞株 (発現宿主): TSA-201 / 器官 (発現宿主): Kidney / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q00959 #3: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #4: 糖 | ChemComp-NAG / |
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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: Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* in the 'Extended' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 7.4 タイプ: COMPLEX 詳細: Sample was heterologously expressed in TSA-201 cells, detergent solubilized, and affinity purified serially to obtain the triheteromeric receptor Entity ID: #1-#2 / 由来: RECOMBINANT | |||||||||||||||||||||||||
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分子量 | 値: 0.5 MDa / 実験値: NO | |||||||||||||||||||||||||
由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) | |||||||||||||||||||||||||
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: TSA-201 | |||||||||||||||||||||||||
緩衝液 | pH: 7.4 | |||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 4 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES / 詳細: This sample was monodisperse | |||||||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / 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: 100 % / 凍結前の試料温度: 291 K / 詳細: Sample was blotted for 3 seconds at blot force 1. |
-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 / Cs: 2.7 mm |
撮影 | 平均露光時間: 22 sec. / 電子線照射量: 52 e/Å2 フィルム・検出器のモデル: GATAN K2 BASE (4k x 4k) 撮影したグリッド数: 1 / 実像数: 1891 |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.13_2998: / 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 | |||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | |||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 6.99 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 40881 / アルゴリズム: FOURIER SPACE / 対称性のタイプ: POINT | |||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT | |||||||||||||||||||||||||||||||||
原子モデル構築 |
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