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基本情報
登録情報 | データベース: EMDB / ID: EMD-9147 | |||||||||
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タイトル | Diheteromeric NMDA receptor GluN1/GluN2A in the '1-Knuckle' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 6.1 | |||||||||
![]() | GluN1/GluN2A diheteromeric NMDAR, at pH 6.1, in 1 micromolar zinc, in the 1-knuckle conformation | |||||||||
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機能・相同性 | ![]() neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / response to environmental enrichment / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling ...neurotransmitter receptor transport, plasma membrane to endosome / regulation of response to alcohol / response to ammonium ion / receptor recycling / directional locomotion / response to environmental enrichment / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / serotonin metabolic process / conditioned place preference / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / response to other organism / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / positive regulation of inhibitory postsynaptic potential / propylene metabolic process / response to glycine / cellular response to magnesium ion / regulation of ARF protein signal transduction / sleep / response to methylmercury / voltage-gated monoatomic cation channel activity / dendritic spine organization / cellular response to dsRNA / response to carbohydrate / regulation of monoatomic cation transmembrane transport / cellular response to lipid / response to morphine / NMDA glutamate receptor activity / locomotion / regulation of NMDA receptor activity / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / calcium ion transmembrane import into cytosol / cellular response to zinc ion / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / regulation of synapse assembly / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of axonogenesis / regulation of dendrite morphogenesis / male mating behavior / dopamine metabolic process / spinal cord development / suckling behavior / action potential / startle response / response to amine / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / modulation of excitatory postsynaptic potential / monoatomic cation transport / response to lithium ion / associative learning / positive regulation of excitatory postsynaptic potential / social behavior / ligand-gated monoatomic ion channel activity / excitatory synapse / cellular response to glycine / positive regulation of dendritic spine maintenance / response to light stimulus / positive regulation of protein targeting to membrane / neuron development / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / postsynaptic density, intracellular component / phosphatase binding / cellular response to manganese ion / glutamate receptor binding / multicellular organismal response to stress / long-term memory / prepulse inhibition / monoatomic cation channel activity / calcium ion homeostasis / regulation of neuron apoptotic process / synaptic cleft / glutamate-gated calcium ion channel activity / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / cell adhesion molecule binding / sensory perception of pain / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / response to amphetamine / ionotropic glutamate receptor signaling pathway / hippocampal mossy fiber to CA3 synapse / neurogenesis 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 5.97 Å | |||||||||
![]() | Jalali-Yazdi F / Chowdhury S / Yoshioka C / Gouaux E | |||||||||
資金援助 | ![]()
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![]() | ![]() 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 |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 25.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 26.6 KB 26.6 KB | 表示 表示 | ![]() |
画像 | ![]() | 160.7 KB | ||
マスクデータ | ![]() | 27 MB | ![]() | |
その他 | ![]() ![]() | 11 MB 11 MB | ||
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 | ![]() 6mm9MC ![]() 9148C ![]() 9149C ![]() 9150C ![]() 9151C ![]() 9152C ![]() 9153C ![]() 9154C ![]() 9155C ![]() 9156C ![]() 9157C ![]() 9158C ![]() 9159C ![]() 9160C ![]() 9161C ![]() 9162C ![]() 9163C ![]() 9164C ![]() 9165C ![]() 6mmaC ![]() 6mmbC ![]() 6mmgC ![]() 6mmhC ![]() 6mmiC ![]() 6mmjC ![]() 6mmkC ![]() 6mmlC ![]() 6mmmC ![]() 6mmnC ![]() 6mmpC ![]() 6mmrC ![]() 6mmsC ![]() 6mmtC ![]() 6mmuC ![]() 6mmvC ![]() 6mmwC ![]() 6mmxC C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
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類似構造データ |
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EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | GluN1/GluN2A diheteromeric NMDAR, at pH 6.1, in 1 micromolar zinc, in the 1-knuckle conformation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.71 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
-マスク #1
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密度ヒストグラム |
-ハーフマップ: half-map for resolution estimation
ファイル | emd_9147_half_map_1.map | ||||||||||||
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注釈 | half-map for resolution estimation | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half-map for resolution estimation
ファイル | emd_9147_half_map_2.map | ||||||||||||
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注釈 | half-map for resolution estimation | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : Diheteromeric NMDA receptor GluN1/GluN2A in the '1-Knuckle' confo...
全体 | 名称: Diheteromeric NMDA receptor GluN1/GluN2A in the '1-Knuckle' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 6.1 |
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要素 |
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-超分子 #1: Diheteromeric NMDA receptor GluN1/GluN2A in the '1-Knuckle' confo...
超分子 | 名称: Diheteromeric NMDA receptor GluN1/GluN2A in the '1-Knuckle' conformation, in complex with glycine and glutamate, in the presence of 1 micromolar zinc chloride, and at pH 6.1 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 詳細: Sample was heterologously expressed in TSA-201 cells, detergent solubilized, and affinity purified |
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由来(天然) | 生物種: ![]() ![]() |
組換発現 | 生物種: ![]() |
分子量 | 理論値: 500 KDa |
-分子 #1: Glutamate receptor ionotropic, NMDA 1
分子 | 名称: Glutamate receptor ionotropic, NMDA 1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 94.189781 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS ...文字列: MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS DDHEGRAAQK RLETLLEERE SKAEKVLQFD PGTKNVTALL MEARELEARV IILSASEDDA ATVYRAAAML NM TGSGYVW LVGEREISGN ALRYAPDGII GLQLINGKNE SAHISDAVGV VAQAVHELLE KENITDPPRG CVGNTNIWKT GPL FKRVLM SSKYADGVTG RVEFNEDGDR KFANYSIMNL QNRKLVQVGI YNGTHVIPND RKIIWPGGET EKPRGYQMST RLKI VTIHQ EPFVYVKPTM SDGTCKEEFT VNGDPVKKVI CTGPNDTSPG SPRHTVPQCC YGFCIDLLIK LARTMNFTYE VHLVA DGKF GTQERVNNSN KKEWNGMMGE LLSGQADMIV APLTINNERA QYIEFSKPFK YQGLTILVKK EIPRSTLDSF MQPFQS TLW LLVGLSVHVV AVMLYLLDRF SPFGRFKVNS EEEEEDALTL SSAMWFSWGV LLNSGIGEGA PRSFSARILG MVWAGFA MI IVASYTANLA AFLVLDRPEE RITGINDPRL RNPSDKFIYA TVKQSSVDIY FRRQVELSTM YRHMEKHNYE SAAEAIQA V RDNKLHAFIW DSAVLEFEAS QKCDLVTTGE LFFRSGFGIG MRKDSPWKQN VSLSILKSHE NGFMEDLDKT WVRYQECDS RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYK |
-分子 #2: Glutamate receptor ionotropic, NMDA 2A
分子 | 名称: Glutamate receptor ionotropic, NMDA 2A / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 93.740352 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MGRLGYWTLL VLPALLVWRD PAQNAAAEKG PPALNIAVLL GHSHDVTERE LRNLWGPEQA TGLPLDVNVV ALLMNRTDPK SLITHVCDL MSGARIHGLV FGDDTDQEAV AQMLDFISSQ TFIPILGIHG GASMIMADKD PTSTFFQFGA SIQQQATVML K IMQDYDWH ...文字列: MGRLGYWTLL VLPALLVWRD PAQNAAAEKG PPALNIAVLL GHSHDVTERE LRNLWGPEQA TGLPLDVNVV ALLMNRTDPK SLITHVCDL MSGARIHGLV FGDDTDQEAV AQMLDFISSQ TFIPILGIHG GASMIMADKD PTSTFFQFGA SIQQQATVML K IMQDYDWH VFSLVTTIFP GYRDFISFIK TTVDNSFVGW DMQNVITLDT SFEDAKTQVQ LKKIHSSVIL LYCSKDEAVL IL SEARSLG LTGYDFFWIV PSLVSGNTEL IPKEFPSGLI SVSYDDWDYS LEARVRDGLG ILTTAASSML EKFSYIPEAK ASC YGQAEK PETPLHTLHQ FMVNVTWDGK DLSFTEEGYQ VHPRLVVIVL NKDREWEKVG KWENQTLSLR HAVWPRYKSF SDCE PDDNH LSIVTLEEAP FVIVEDIDPL TETCVRNTVP CRKFVKINNS TNEGMNVKKC CKGFCIDILK KLSRTVKFTY DLYLV TNGK HGKKVNNVWN GMIGEVVYQR AVMAVGSLTI NEERSEVVDF SVPFVETGIS VMVSRSNGTV SPSAFLEPFS ASVWVM MFV MLLIVSAIAV FVFEYFSPVG YNRNLAKGKA PHGPSFTIGK AIWLLWGLVF NNSVPVQNPK GTTSKIMVSV WAFFAVI FL ASYTANLAAF MIQEEFVDQV TGLSDKKFQR PHDYSPPFRF GTVPNGSTER NIRNNYPYMH QYMTRFNQRG VEDALVSL K TGKLDAFIYD AAVLNYKAGR DEGCKLVTIG SGYIFATTGY GIALQKGSPW KRQIDLALLQ FVGDGEMEEL ETLWLTGIC HNEKNEVMSS QLDIDNMAGV FYMLAAAMAL SLITFIW |
-分子 #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 3 / コピー数: 34 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 4.0 mg/mL | |||||||||||||||
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緩衝液 | pH: 6.1 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 雰囲気: AIR | |||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 291 K / 装置: FEI VITROBOT MARK IV / 詳細: Sample was blotted for 3 seconds at blot force 1.. | |||||||||||||||
詳細 | This sample was monodisperse |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | 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: 2163 / 平均露光時間: 22.0 sec. / 平均電子線量: 52.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
初期モデル |
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精密化 | プロトコル: RIGID BODY FIT | ||||||||||
得られたモデル | ![]() PDB-6mm9: |