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基本情報
登録情報 | ![]() | ||||||||||||||||||
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タイトル | Structure of GluN1a-GluN2D NMDA receptor in complex with agonists glycine and glutamate. | ||||||||||||||||||
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![]() | ion channel / cryo-EM structure / glutamate receptor / synaptic protein / ELECTRON TRANSPORT | ||||||||||||||||||
機能・相同性 | ![]() excitatory chemical synaptic transmission / regulation of sensory perception of pain / cellular response to L-glutamate / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity ...excitatory chemical synaptic transmission / regulation of sensory perception of pain / cellular response to L-glutamate / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / voltage-gated monoatomic cation channel activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / Neurexins and neuroligins / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / glycine binding / positive regulation of calcium ion transport into cytosol / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / startle response / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / monoatomic cation transport / positive regulation of excitatory postsynaptic potential / Long-term potentiation / ligand-gated monoatomic ion channel activity / excitatory synapse / calcium ion homeostasis / synaptic cleft / glutamate-gated calcium ion channel activity / glutamate-gated receptor activity / presynaptic active zone membrane / EPHB-mediated forward signaling / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / Ras activation upon Ca2+ influx through NMDA receptor / ionotropic glutamate receptor signaling pathway / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic / adult locomotory behavior / excitatory postsynaptic potential / regulation of membrane potential / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / long-term synaptic potentiation / postsynaptic density membrane / visual learning / regulation of synaptic plasticity / brain development / terminal bouton / synaptic vesicle / signaling receptor activity / amyloid-beta binding / RAF/MAP kinase cascade / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / postsynaptic density / calmodulin binding / neuron projection / glutamatergic synapse / synapse / dendrite / calcium ion binding / endoplasmic reticulum membrane / protein-containing complex binding / cell surface / positive regulation of transcription by RNA polymerase II / plasma membrane / cytoplasm 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: 3.9 Å | ||||||||||||||||||
![]() | Zhang JL / Zhu SJ / Zhang M | ||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits. 著者: Jilin Zhang / Ming Zhang / Qinrui Wang / Han Wen / Zheyi Liu / Fangjun Wang / Yuhang Wang / Fenyong Yao / Nan Song / Zengwei Kou / Yang Li / Fei Guo / Shujia Zhu / ![]() 要旨: N-methyl-D-aspartate (NMDA) receptors are heterotetramers comprising two GluN1 and two alternate GluN2 (N2A-N2D) subunits. Here we report full-length cryo-EM structures of the human N1-N2D di- ...N-methyl-D-aspartate (NMDA) receptors are heterotetramers comprising two GluN1 and two alternate GluN2 (N2A-N2D) subunits. Here we report full-length cryo-EM structures of the human N1-N2D di-heterotetramer (di-receptor), rat N1-N2C di-receptor and N1-N2A-N2C tri-heterotetramer (tri-receptor) at a best resolution of 3.0 Å. The bilobate N-terminal domain (NTD) in N2D intrinsically adopts a closed conformation, leading to a compact NTD tetramer in the N1-N2D receptor. Additionally, crosslinking the ligand-binding domain (LBD) of two N1 protomers significantly elevated the channel open probability (Po) in N1-N2D di-receptors. Surprisingly, the N1-N2C di-receptor adopted both symmetric (minor) and asymmetric (major) conformations, the latter further locked by an allosteric potentiator, PYD-106, binding to a pocket between the NTD and LBD in only one N2C protomer. Finally, the N2A and N2C subunits in the N1-N2A-N2C tri-receptor display a conformation close to one protomer in the N1-N2A and N1-N2C di-receptors, respectively. These findings provide a comprehensive structural understanding of diverse function in major NMDA receptor subtypes. | ||||||||||||||||||
履歴 |
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構造の表示
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-EMDBアーカイブ
マップデータ | ![]() | 34.5 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 21.8 KB 21.8 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.3 KB | 表示 | ![]() |
画像 | ![]() | 38.7 KB | ||
マスクデータ | ![]() | 67 MB | ![]() | |
その他 | ![]() ![]() | 61.8 MB 61.8 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 | ![]() 7yflMC ![]() 7yffC ![]() 7yfgC ![]() 7yfhC ![]() 7yfiC ![]() 7yfmC ![]() 7yfoC ![]() 7yfrC ![]() 8hdkC 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 | 類似検索 - 機能・相同性 ![]() |
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リンク
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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ボクセルのサイズ | X=Y=Z: 1.06 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
-マスク #1
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_33792_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_33792_half_map_2.map | ||||||||||||
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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 : NMDA receptor with NMDA 1 incorperated with NMDA 2D
全体 | 名称: NMDA receptor with NMDA 1 incorperated with NMDA 2D |
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要素 |
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-超分子 #1: NMDA receptor with NMDA 1 incorperated with NMDA 2D
超分子 | 名称: NMDA receptor with NMDA 1 incorperated with NMDA 2D / 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: ![]() |
分子量 | 理論値: 384.54 kDa/nm |
-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: 95.236078 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MSTMRLLTLA LLFSCSVARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYS W NHIILLVS ...文字列: MSTMRLLTLA LLFSCSVARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYS W NHIILLVS DDHEGRAAQK RLETLLEERE SKAEKVLQFD PGTKNVTALL MEAKELEARV IILSASEDDA ATVYRAAAML NM TGSGYVW LVGEREISGN ALRYAPDGIL GLQLINGKNE SAHISDAVGV VAQAVHELLE KENITDPPRG CVGNTNIWKT GPL FKRVLM SSKYADGVTG RVEFNEDGDR KFANYSIMNL QNRKLVQVGI YNGTHVIPND RKIIWPGGET EKPRGYQMST RLKI VTIHQ EPFVYVKPTL 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 IFIEIAYKRH KDARRKQ UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-分子 #2: Glutamate receptor ionotropic, NMDA 2D
分子 | 名称: Glutamate receptor ionotropic, NMDA 2D / 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: 97.226414 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MRGAGGPRGP RGPAKMLLLL ALACASPFPE EAPGPGGAGG PGGGLGGARP LNVALVFSGP AYAAEAARLG PAVAAAVRSP GLDVRPVAL VLNGSDPRSL VLQLCDLLSG LRVHGVVFED DSRAPAVAPI LDFLSAQTSL PIVAVHGGAA LVLTPKEKGS T FLQLGSST ...文字列: MRGAGGPRGP RGPAKMLLLL ALACASPFPE EAPGPGGAGG PGGGLGGARP LNVALVFSGP AYAAEAARLG PAVAAAVRSP GLDVRPVAL VLNGSDPRSL VLQLCDLLSG LRVHGVVFED DSRAPAVAPI LDFLSAQTSL PIVAVHGGAA LVLTPKEKGS T FLQLGSST EQQLQVIFEV LEEYDWTSFV AVTTRAPGHR AFLSYIEVLT DGSLVGWEHR GALTLDPGAG EAVLSAQLRS VS AQIRLLF CAREEAEPVF RAAEEAGLTG SGYVWFMVGP QLAGGGGSGA PGEPPLLPGG APLPAGLFAV RSAGWRDDLA RRV AAGVAV VARGAQALLR DYGFLPELGH DCRAQNRTHR GESLHRYFMN ITWDNRDYSF NEDGFLVNPS LVVISLTRDR TWEV VGSWE QQTLRLKYPL WSRYGRFLQP VDDTQHLTVA TLEERPFVIV EPADPISGTC IRDSVPCRSQ LNRTHSPPPD APRPE KRCC KGFCIDILKR LAHTIGFSYD LYLVTNGKHG KKIDGVWNGM IGEVFYQRAD MAIGSLTINE ERSEIVDFSV PFVETG ISV MVARSNGTVS PSAFLEPYSP AVWVMMFVMC LTVVAVTVFI FEYLSPVGYN RSLATGKRPG GSTFTIGKSI WLLWALV FN NSVPVENPRG TTSKIMVLVW AFFAVIFLAS YTANLAAFMI QEEYVDTVSG LSDRKFQRPQ EQYPPLKFGT VPNGSTEK N IRSNYPDMHS YMVRYNQPRV EEALTQLKAG KLDAFIYDAA VLNYMARKDE GCKLVTIGSG KVFATTGYGI ALHKGSRWK RPIDLALLQF LGDDEIEMLE RLWLSGICHN DKIEVMSSKL DIDNMAGVFY MLLVAMGLSL LVFAWEHLVY WRLRHCLGPA ASAWSHPQF EK UniProtKB: Glutamate receptor ionotropic, NMDA 2D |
-分子 #4: GLYCINE
分子 | 名称: GLYCINE / タイプ: ligand / ID: 4 / 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 #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: 10 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-分子 #6: GLUTAMIC ACID
分子 | 名称: GLUTAMIC ACID / タイプ: ligand / ID: 6 / 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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![]() | 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: 8 |
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 60 sec. / 前処理 - 雰囲気: AIR / 前処理 - 気圧: 101.325 kPa |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 281 K / 装置: FEI VITROBOT MARK IV / 詳細: Blot for 3 seconds before plunging. |
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: DIRECT ELECTRON DE-10 (5k x 4k) 検出モード: SUPER-RESOLUTION / デジタル化 - 画像ごとのフレーム数: 1-40 / 撮影したグリッド数: 1 / 実像数: 3840 / 平均電子線量: 60.0 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 / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.5 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |