+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-44586 | |||||||||
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タイトル | Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, glutamate, and EU-1622-A, in open-channel conformation, C1 symmetry | |||||||||
マップデータ | B-factor sharpened map | |||||||||
試料 |
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キーワード | Ionotropic glutamate receptor / synaptic membrane protein / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 organelle / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange ...organelle / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / response to morphine / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / neuromuscular process / glutamate binding / protein heterotetramerization / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / regulation of axonogenesis / regulation of dendrite morphogenesis / positive regulation of calcium ion transport into cytosol / male mating behavior / glycine binding / suckling behavior / startle response / response to amine / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / 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 / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / cellular response to manganese ion / glutamate receptor binding / long-term memory / prepulse inhibition / monoatomic cation channel activity / calcium ion homeostasis / regulation of neuron apoptotic process / synaptic cleft / glutamate-gated receptor activity / response to fungicide / presynaptic active zone membrane / glutamate-gated calcium ion channel activity / 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 / positive regulation of synaptic transmission, glutamatergic / adult locomotory behavior / regulation of membrane potential / excitatory postsynaptic potential / learning / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / visual learning / calcium channel activity / regulation of synaptic plasticity / response to organic cyclic compound / terminal bouton / cerebral cortex development / memory / synaptic vesicle membrane / intracellular calcium ion homeostasis / response to calcium ion / neuron cellular homeostasis / calcium ion transport / rhythmic process / synaptic vesicle / signaling receptor activity / presynaptic membrane / amyloid-beta binding / protein-containing complex assembly / chemical synaptic transmission / postsynaptic membrane / response to ethanol / negative regulation of neuron apoptotic process / transcription by RNA polymerase II / dendritic spine / postsynaptic density 類似検索 - 分子機能 | |||||||||
生物種 | Rattus norvegicus (ドブネズミ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.81 Å | |||||||||
データ登録者 | Chou T-H / Furukawa H | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Nature / 年: 2024 タイトル: Molecular mechanism of ligand gating and opening of NMDA receptor. 著者: Tsung-Han Chou / Max Epstein / Russell G Fritzemeier / Nicholas S Akins / Srinu Paladugu / Elijah Z Ullman / Dennis C Liotta / Stephen F Traynelis / Hiro Furukawa / 要旨: Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor ...Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor (NMDAR) is unique among all ligand-gated channels, requiring two ligands-glutamate and glycine-for activation. These receptors function as heterotetrameric ion channels, with the channel opening dependent on the simultaneous binding of glycine and glutamate to the extracellular ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, respectively. The exact molecular mechanism for channel gating by the two ligands has been unclear, particularly without structures representing the open channel and apo states. Here we show that the channel gate opening requires tension in the linker connecting the LBD and transmembrane domain (TMD) and rotation of the extracellular domain relative to the TMD. Using electron cryomicroscopy, we captured the structure of the GluN1-GluN2B (GluN1-2B) NMDAR in its open state bound to a positive allosteric modulator. This process rotates and bends the pore-forming helices in GluN1 and GluN2B, altering the symmetry of the TMD channel from pseudofourfold to twofold. Structures of GluN1-2B NMDAR in apo and single-liganded states showed that binding of either glycine or glutamate alone leads to distinct GluN1-2B dimer arrangements but insufficient tension in the LBD-TMD linker for channel opening. This mechanistic framework identifies a key determinant for channel gating and a potential pharmacological strategy for modulating NMDAR activity. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_44586.map.gz | 230.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-44586-v30.xml emd-44586.xml | 21.3 KB 21.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_44586.png | 35.6 KB | ||
Filedesc metadata | emd-44586.cif.gz | 7.1 KB | ||
その他 | emd_44586_additional_1.map.gz emd_44586_half_map_1.map.gz emd_44586_half_map_2.map.gz | 230 MB 226.4 MB 226.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-44586 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44586 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_44586_validation.pdf.gz | 924.5 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_44586_full_validation.pdf.gz | 924.1 KB | 表示 | |
XML形式データ | emd_44586_validation.xml.gz | 15.9 KB | 表示 | |
CIF形式データ | emd_44586_validation.cif.gz | 18.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44586 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44586 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_44586.map.gz / 形式: CCP4 / 大きさ: 244.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | B-factor sharpened map | ||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.861 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-追加マップ: Local refined map focused on TMD
ファイル | emd_44586_additional_1.map | ||||||||||||
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注釈 | Local refined map focused on TMD | ||||||||||||
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 B
ファイル | emd_44586_half_map_1.map | ||||||||||||
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注釈 | Half map B | ||||||||||||
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 A
ファイル | emd_44586_half_map_2.map | ||||||||||||
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注釈 | Half map A | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Di-heterotetrameric GluN1-GluN2B NMDA receptors
全体 | 名称: Di-heterotetrameric GluN1-GluN2B NMDA receptors |
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要素 |
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-超分子 #1: Di-heterotetrameric GluN1-GluN2B NMDA receptors
超分子 | 名称: Di-heterotetrameric GluN1-GluN2B NMDA receptors / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
分子量 | 理論値: 400 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: Rattus norvegicus (ドブネズミ) |
分子量 | 理論値: 95.225883 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MSTMHLLTFA LLFSCSFARA ASDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL QATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS ...文字列: MSTMHLLTFA LLFSCSFARA ASDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL QATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS DDHEGRAAQK RLETLLEERE SKAEKVLQFD PGTKNVTALL MEARELEARV IILSASEDDA ATVYRAAAML DM TGSGYVW LVGEREISGN ALRYAPDGII GLQLINGKNE SAHISDAVGV VAQAVHELLE KENITDPPRG CVGNTNIWKT GPL FKRVLM SSKYADGVTG RVEFNEDGDR KFAQYSIMNL QNRKLVQVGI YNGTHVIPND RKIIWPGGET EKPRGYQMST RLKI VTIHQ EPFVYVKPTM SDGTCKEEFT VNGDPVKKVI CTGPNDTSPG SPRHTVPQCC YGFCIDLLIK LARTMQFTYE VHLVA DGKF GTQERVQNSN 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 MRKDSPWKQQ VSLSILKSHE NGFMEDLDKT WVRYQECDS RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYKRH KDANGAQ UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-分子 #2: Glutamate receptor
分子 | 名称: Glutamate receptor / 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: Rattus norvegicus (ドブネズミ) |
分子量 | 理論値: 98.888945 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGTMRLFLLA VLFLFSFARA TGWSHPQFEK GGGSGGGSGG SAWSHPQFEK GALVPRGRSQ KSPPSIGIAV ILVGTSDEVA IKDAHEKDD FHHLSVVPRV ELVAMNETDP KSIITRICDL MSDRKIQGVV FADDTDQEAI AQILDFISAQ TLTPILGIHG G SSMIMADK ...文字列: MGTMRLFLLA VLFLFSFARA TGWSHPQFEK GGGSGGGSGG SAWSHPQFEK GALVPRGRSQ KSPPSIGIAV ILVGTSDEVA IKDAHEKDD FHHLSVVPRV ELVAMNETDP KSIITRICDL MSDRKIQGVV FADDTDQEAI AQILDFISAQ TLTPILGIHG G SSMIMADK DESSMFFQFG PSIEQQASVM LNIMEEYDWY IFSIVTTYFP GYQDFVNKIR STIENSFVGW ELEEVLLLDM SL DDGDSKI QNQLKKLQSP IILLYCTKEE ATYIFEVANS VGLTGYGYTW IVPSLVAGDT DTVPSEFPTG LISVSYDEWD YGL PARVRD GIAIITTAAS DMLSEHSFIP EPKSSCYNTH EKRIYQSNML NRYLINVTFE GRNLSFSEDG YQMHPKLVII LLNK ERKWE RVGKWKDKSL QMKYYVWPRM CPETEEQEDD HLSIVTLEEA PFVIVESVDP LSGTCMRNTV PCQKRIISEN KTDEE PGYI KKCCKGFCID ILKKISKSVK FTYDLYLVTN GKHGKKINGT WNGMIGEVVM KRAYMAVGSL TINEERSEVV DFSVPF IET GISVMVSRSN GTVSPSAFLE PFSADVWVMM FVMLLIVSAV AVFVFEYFSP VGYNRCLADG REPGGPSFTI GKAIWLL WG LVFNNSVPVQ NPKGTTSKIM VSVWAFFAVI FLASYTANLA AFMIQEEYVD QVSGLSDKKF QRPNDFSPPF RFGTVPNG S TERNIRNNYA EMHAYMGKFN QRGVDDALLS LKTGKLDAFI YDAAVLNYMA GRDEGCKLVT IGSGKVFAST GYGIAIQKD SGWKRQVDLA ILQLFGDGEM EELEALWLTG ICHNEKNEVM SSQLDIDNMA GVFYMLGAAM ALSLITFICE HLFYWQFRHS FMG UniProtKB: Glutamate receptor |
-分子 #3: GLYCINE
分子 | 名称: GLYCINE / タイプ: ligand / ID: 3 / コピー数: 2 / 式: GLY |
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分子量 | 理論値: 75.067 Da |
Chemical component information | ChemComp-GLY: |
-分子 #4: GLUTAMIC ACID
分子 | 名称: GLUTAMIC ACID / タイプ: ligand / ID: 4 / コピー数: 2 / 式: GLU |
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分子量 | 理論値: 147.129 Da |
Chemical component information | ChemComp-GLU: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 4 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | モデル: UltrAuFoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 35 sec. |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 85 % / チャンバー内温度: 285 K |
-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 K3 BIOQUANTUM (6k x 4k) 平均電子線量: 66.3 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD 最大 デフォーカス(公称値): 2.8000000000000003 µm 最小 デフォーカス(公称値): 1.4000000000000001 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |