+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6mmv | |||||||||
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タイトル | Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* Extracellular Domain in the '2-Knuckle-Asymmetric' 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 / Ligand-gated Ion Channel / NMDA Receptor / ionotropic Glutamate Receptors / membrane protein | |||||||||
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 / response to hydrogen sulfide / positive regulation of inhibitory postsynaptic potential / directional locomotion / response to environmental enrichment / response to other organism / response to methylmercury ...neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / response to hydrogen sulfide / positive regulation of inhibitory postsynaptic potential / directional locomotion / response to environmental enrichment / response to other organism / response to methylmercury / regulation of ARF protein signal transduction / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / serotonin metabolic process / olfactory learning / response to carbohydrate / dendritic branch / cellular response to dsRNA / conditioned taste aversion / cellular response to lipid / regulation of respiratory gaseous exchange / cellular response to magnesium ion / protein localization to postsynaptic membrane / conditioned place preference / propylene metabolic process / response to glycine / sleep / locomotion / dendritic spine organization / response to manganese ion / regulation of monoatomic cation transmembrane transport / voltage-gated monoatomic cation channel activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / NMDA glutamate receptor activity / regulation of NMDA receptor activity / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor complex / response to morphine / cellular response to zinc ion / calcium ion transmembrane import into cytosol / glutamate receptor signaling pathway / glutamate binding / neuromuscular process / protein heterotetramerization / positive regulation of calcium ion transport into cytosol / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / glycine binding / regulation of axonogenesis / regulation of dendrite morphogenesis / male mating behavior / spinal cord development / action potential / suckling behavior / dopamine metabolic process / startle response / response to amine / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / modulation of excitatory postsynaptic potential / response to lithium ion / associative learning / monoatomic cation transport / social behavior / excitatory synapse / ligand-gated monoatomic ion channel activity / positive regulation of excitatory postsynaptic potential / regulation of postsynaptic membrane potential / cellular response to glycine / neuron development / postsynaptic density, intracellular component / positive regulation of dendritic spine maintenance / response to light stimulus / positive regulation of protein targeting to membrane / multicellular organismal response to stress / Unblocking of NMDA receptors, glutamate binding and activation / cellular response to manganese ion / phosphatase binding / glutamate receptor binding / long-term memory / regulation of neuron apoptotic process / monoatomic cation channel activity / prepulse inhibition / calcium ion homeostasis / synaptic cleft / glutamate-gated receptor activity / cell adhesion molecule binding / response to fungicide / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / sensory perception of pain / response to amphetamine / ionotropic glutamate receptor signaling pathway / protein tyrosine kinase binding 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: 4.71 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 | 6mmv.cif.gz | 483.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6mmv.ent.gz | 390.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6mmv.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 | 6mmv_validation.pdf.gz | 1.7 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6mmv_full_validation.pdf.gz | 1.8 MB | 表示 | |
XML形式データ | 6mmv_validation.xml.gz | 81.4 KB | 表示 | |
CIF形式データ | 6mmv_validation.cif.gz | 116.9 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/mm/6mmv ftp://data.pdbj.org/pub/pdb/validation_reports/mm/6mmv | HTTPS FTP |
-関連構造データ
関連構造データ | 9163MC 9147C 9148C 9149C 9150C 9151C 9152C 9153C 9154C 9155C 9156C 9157C 9158C 9159C 9160C 9161C 9162C 9164C 9165C 6mm9C 6mmaC 6mmbC 6mmgC 6mmhC 6mmiC 6mmjC 6mmkC 6mmlC 6mmmC 6mmnC 6mmpC 6mmrC 6mmsC 6mmtC 6mmuC 6mmwC 6mmxC 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: 89853.656 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 / Variant: 1a / 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: 89580.523 Da / 分子数: 1 / 断片: UNP residues 1-800 / 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: タンパク質 | | 分子量: 89543.477 Da / 分子数: 1 / 断片: UNP residues 1-800 / 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 #4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 糖 | ChemComp-NAG / Has protein modification | 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 |
-試料調製
構成要素 | 名称: Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* Extracellular Domain in the '2-Knuckle-Asymmetric' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc ...名称: Triheteromeric NMDA receptor GluN1/GluN2A/GluN2A* Extracellular Domain in the '2-Knuckle-Asymmetric' 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-#3 / 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 FIELD / 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: 4.71 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 68275 / 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 | 3D fitting-ID: 1 / Source name: PDB / タイプ: experimental model
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