+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-21680 | |||||||||
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タイトル | GluN1b-GluN2B NMDA receptor in complex with GluN1 antagonist L689,560, class 1 | |||||||||
マップデータ | B factor sharpened (-150) | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration ...neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / Assembly and cell surface presentation of NMDA receptors / response to hydrogen sulfide / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / dendritic branch / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / response to other organism / positive regulation of inhibitory postsynaptic potential / apical dendrite / propylene metabolic process / response to glycine / regulation of ARF protein signal transduction / fear response / response to methylmercury / voltage-gated monoatomic cation channel activity / positive regulation of cysteine-type endopeptidase activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / cellular response to lipid / response to morphine / NMDA glutamate receptor activity / positive regulation of glutamate secretion / response to growth hormone / Synaptic adhesion-like molecules / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / response to manganese ion / NMDA selective glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / glutamate-gated calcium ion channel activity / glutamate binding / neuromuscular process / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / regulation of synapse assembly / action potential / glycine binding / positive regulation of calcium ion transport into cytosol / regulation of dendrite morphogenesis / regulation of axonogenesis / male mating behavior / heterocyclic compound binding / suckling behavior / startle response / behavioral response to pain / response to amine / monoatomic cation transmembrane transport / receptor clustering / monoatomic cation transport / regulation of neuronal synaptic plasticity / associative learning / positive regulation of excitatory postsynaptic potential / regulation of MAPK cascade / social behavior / response to magnesium ion / ligand-gated monoatomic ion channel activity / cellular response to organic cyclic compound / extracellularly glutamate-gated ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / small molecule binding / neuron development / Unblocking of NMDA receptors, glutamate binding and activation / behavioral fear response / regulation of postsynaptic membrane potential / postsynaptic density, intracellular component / phosphatase binding / cellular response to manganese ion / calcium ion homeostasis / glutamate receptor binding / D2 dopamine receptor binding / prepulse inhibition / multicellular organismal response to stress / monoatomic cation channel activity / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / regulation of neuron apoptotic process / response to electrical stimulus / synaptic cleft / glutamate-gated receptor activity / presynaptic active zone membrane 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: 4.03 Å | |||||||||
データ登録者 | Chou T / Tajima N / Furukawa H | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Cell / 年: 2020 タイトル: Structural Basis of Functional Transitions in Mammalian NMDA Receptors. 著者: Tsung-Han Chou / Nami Tajima / Annabel Romero-Hernandez / Hiro Furukawa / 要旨: Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of ...Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of GluN1 and GluN2 subunits, which bind glycine and glutamate, respectively, to activate their ion channels. Despite importance in brain physiology, the precise mechanisms by which activation and inhibition occur via subunit-specific binding of agonists and antagonists remain largely unknown. Here, we show the detailed patterns of conformational changes and inter-subunit and -domain reorientation leading to agonist-gating and subunit-dependent competitive inhibition by providing multiple structures in distinct ligand states at 4 Å or better. The structures reveal that activation and competitive inhibition by both GluN1 and GluN2 antagonists occur by controlling the tension of the linker between the ligand-binding domain and the transmembrane ion channel of the GluN2 subunit. Our results provide detailed mechanistic insights into NMDAR pharmacology, activation, and inhibition, which are fundamental to the brain physiology. | |||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_21680.map.gz | 59.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-21680-v30.xml emd-21680.xml | 15.6 KB 15.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_21680.png | 61.6 KB | ||
その他 | emd_21680_additional.map.gz | 59.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-21680 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21680 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_21680_validation.pdf.gz | 528 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_21680_full_validation.pdf.gz | 527.6 KB | 表示 | |
XML形式データ | emd_21680_validation.xml.gz | 6.4 KB | 表示 | |
CIF形式データ | emd_21680_validation.cif.gz | 7.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21680 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21680 | HTTPS FTP |
-関連構造データ
関連構造データ | 6whyMC 6usuC 6usvC 6whrC 6whsC 6whtC 6whuC 6whvC 6whwC 6whxC 6wi0C 6wi1C M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ |
-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_21680.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | B factor sharpened (-150) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.37 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
-追加マップ: Unsharpened map
ファイル | emd_21680_additional.map | ||||||||||||
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注釈 | Unsharpened map | ||||||||||||
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 : NMDA receptor GluN1b/2B functional ion channel complex
全体 | 名称: NMDA receptor GluN1b/2B functional ion channel complex |
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要素 |
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-超分子 #1: NMDA receptor GluN1b/2B functional ion channel complex
超分子 | 名称: NMDA receptor GluN1b/2B functional ion channel complex 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) |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
-分子 #1: Ionotropic glutamate receptor , NMDA receptor GluN1b
分子 | 名称: Ionotropic glutamate receptor , NMDA receptor GluN1b 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: 108.085633 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 SKSKKRNYEN LDQLSYDNKR GPKAEKVLQF DPGTKNVTAL LMEARELEAR VI ILSASED DAATVYRAAA MLDMTGSGYV WLVGEREISG NALRYAPDGI IGLQLINGKN ESAHISDAVG VVAQAVHELL EKE NITDPP RGCVGNTNIW KTGPLFKRVL MSSKYADGVT GRVEFNEDGD RKFAQYSIMN LQNRKLVQVG IYNGTHVIPN DRKI IWPGG ETEKPRGYQM STRLKIVTIH QEPFVYVKPT MSDGTCKEEF TVNGDPVKKV ICTGPNDTSP GSPRHTVPQC CYGFC IDLL IKLARTMQFT YEVHLVADGK FGTQERVQNS NKKEWNGMMG ELLSGQADMI VAPLTINNER AQYIEFSKPF KYQGLT ILV KKEIPRSTLD SFMQPFQSTL WLLVGLSVHV VAVMLYLLDR FSPFGRFKVN SQSESTDALT LSSAMWFSWG VLLNSGI GE GAPRSFSARI LGMVWAGFAM IIVASYTANL AAFLVLDRPE ERITGINDPR LRNPSDKFIY ATVKQSSVDI YFRRQVEL S TMYRHMEKHN YESAAEAIQA VRDNKLHAFI WDSAVLEFEA SQKCDLVTTG ELFFRSGFGI GMRKDSPWKQ QVSLSILKS HENGFMEDLD KTWVRYQECD SRSNAPATLT CENMAGVFML VAGGIVAGIF LIFIEIAYKR HKDARRKQMQ LAFAAVNVWR KNLQDRKSG RAEPDPKKKA TFRAITSTLA SSFKRRRSSK DTSTGGGRGA LQNQKDTVLP RRAIEREEGQ LQLCSRHRES |
-分子 #2: Ionotropic glutamate receptor , NMDA receptor GluN2B
分子 | 名称: Ionotropic glutamate receptor , NMDA receptor GluN2B 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: 98.845859 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 GRDLSFSEDG YQMHPKLVII LLNK ERKWE RVGKWKDKSL QMKYYVWPRM CPETEEQEDD HLSIVTLEEA PFVIVESVDP LSGTCMRNTV PCQKRIISEN KTDEE PGYI KKCCKGFCID ILKKISKSVK FTYDLYLVTN GKHGKKINGT WNGMIGEVVM KRAYMAVGSL TINEERSEVV DFSVPF IET GISVMVSRSN GTVSPSAFLE PFSACVWVMM FVMLLIVSAV AVFVFEYFSP VGYNRSLADG 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 ALSLITFISE HLFYWQFRHS FMG |
-分子 #4: (2R,4S)-5,7-dichloro-4-[(phenylcarbamoyl)amino]-1,2,3,4-tetrahydr...
分子 | 名称: (2R,4S)-5,7-dichloro-4-[(phenylcarbamoyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid タイプ: ligand / ID: 4 / コピー数: 2 / 式: QGM |
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分子量 | 理論値: 380.225 Da |
Chemical component information | ChemComp-QGM: |
-分子 #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 5 / コピー数: 2 / 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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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 85 % / チャンバー内温度: 295 K / 装置: FEI VITROBOT MARK IV |
-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 SUMMIT (4k x 4k) 平均電子線量: 64.5 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 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: OTHER / 詳細: Ab initio reconstruction |
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最終 再構成 | 想定した対称性 - 点群: C2 (2回回転対称) / 解像度のタイプ: BY AUTHOR / 解像度: 4.03 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cisTEM (ver. 1.0.0) / 使用した粒子像数: 194228 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |