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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Human GluN1a-GluN2A-GluN2C triheteromeric NMDA receptor in complex with Nb-4 | |||||||||
![]() | B-factor sharpened map | |||||||||
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機能・相同性 | ![]() excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / serotonin metabolic process / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / sleep / activation of cysteine-type endopeptidase activity / glutamate receptor signaling pathway ...excitatory chemical synaptic transmission / directional locomotion / Synaptic adhesion-like molecules / serotonin metabolic process / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / sleep / activation of cysteine-type endopeptidase activity / glutamate receptor signaling pathway / 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 / dopamine metabolic process / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / startle response / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / positive regulation of excitatory postsynaptic potential / Long-term potentiation / ligand-gated monoatomic ion channel activity / neuromuscular process controlling balance / excitatory synapse / glutamate-gated calcium ion channel activity / calcium ion homeostasis / synaptic cleft / MECP2 regulates neuronal receptors and channels / sensory perception of pain / EPHB-mediated forward signaling / response to amphetamine / Ras activation upon Ca2+ influx through NMDA receptor / ionotropic glutamate receptor signaling pathway / positive regulation of synaptic transmission, glutamatergic / neurogenesis / 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 / cytoplasmic vesicle membrane / regulation of synaptic plasticity / protein catabolic process / brain development / negative regulation of protein catabolic process / terminal bouton / memory / response to wounding / synaptic vesicle / signaling receptor activity / presynaptic membrane / amyloid-beta binding / RAF/MAP kinase cascade / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / postsynaptic density / learning or memory / calmodulin binding / neuron projection / response to xenobiotic stimulus / positive regulation of apoptotic process / glutamatergic synapse / dendrite / synapse / calcium ion binding / endoplasmic reticulum membrane / protein-containing complex binding / cell surface / positive regulation of transcription by RNA polymerase II / zinc ion binding / 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: 4.24 Å | |||||||||
![]() | Chou T-H / Furukawa H | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs. 著者: Tsung-Han Chou / Hyunook Kang / Noriko Simorowski / Stephen F Traynelis / Hiro Furukawa / ![]() 要旨: Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. ...Neurotransmission mediated by diverse subtypes of N-methyl-D-aspartate receptors (NMDARs) is fundamental for basic brain functions and development as well as neuropsychiatric diseases and disorders. NMDARs are glycine- and glutamate-gated ion channels that exist as heterotetramers composed of obligatory GluN1 and GluN2(A-D) and/or GluN3(A-B). The GluN2C and GluN2D subunits form ion channels with distinct properties and spatio-temporal expression patterns. Here, we provide the structures of the agonist-bound human GluN1-2C NMDAR in the presence and absence of the GluN2C-selective positive allosteric potentiator (PAM), PYD-106, the agonist-bound GluN1-2A-2C tri-heteromeric NMDAR, and agonist-bound GluN1-2D NMDARs by single-particle electron cryomicroscopy. Our analysis shows unique inter-subunit and domain arrangements of the GluN2C NMDARs, which contribute to functional regulation and formation of the PAM binding pocket and is distinct from GluN2D NMDARs. Our findings here provide the fundamental blueprint to study GluN2C- and GluN2D-containing NMDARs, which are uniquely involved in neuropsychiatric disorders. | |||||||||
履歴 |
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構造の表示
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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 | ![]() | 226.9 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 21.4 KB 21.4 KB | 表示 表示 | ![]() |
画像 | ![]() | 32.3 KB | ||
その他 | ![]() ![]() | 59.1 MB 59.1 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 752.5 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 752.1 KB | 表示 | |
XML形式データ | ![]() | 16.4 KB | 表示 | |
CIF形式データ | ![]() | 19.2 KB | 表示 | |
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 | ![]() 8e99MC ![]() 8e92C ![]() 8e93C ![]() 8e94C ![]() 8e96C ![]() 8e97C ![]() 8e98C 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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注釈 | B-factor sharpened map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.856 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
-ハーフマップ: Half map 1
ファイル | emd_27961_half_map_1.map | ||||||||||||
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注釈 | Half map 1 | ||||||||||||
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 2
ファイル | emd_27961_half_map_2.map | ||||||||||||
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注釈 | Half map 2 | ||||||||||||
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 : Hetero-tetrameric GluN1a-GluN2C NMDA receptors
全体 | 名称: Hetero-tetrameric GluN1a-GluN2C NMDA receptors |
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要素 |
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-超分子 #1: Hetero-tetrameric GluN1a-GluN2C NMDA receptors
超分子 | 名称: Hetero-tetrameric GluN1a-GluN2C NMDA receptors / タイプ: complex / キメラ: Yes / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 |
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由来(天然) | 生物種: ![]() |
-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: 95.081688 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSTMHLLTFA LLFSCSFARA ASDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYS W NHIILLVS ...文字列: MSTMHLLTFA LLFSCSFARA ASDPKIVNIG 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 KDANGAQ |
-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: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 97.770867 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: GSGATNFSLL KQAGDVEENP GPMGTMRLFL LAVLFLFSFA RATGGPPALN IAVMLGHSHD VTERELRTLW GPEQAAGLPL DVNVVALLM NRTDPKSLIT HVCDLMSGAR IHGLVFGDDT DQEAVAQMLD FISSHTFVPI LGIHGGASMI MADKDPTSTF F QFGASIQQ ...文字列: GSGATNFSLL KQAGDVEENP GPMGTMRLFL LAVLFLFSFA RATGGPPALN IAVMLGHSHD VTERELRTLW GPEQAAGLPL DVNVVALLM NRTDPKSLIT HVCDLMSGAR IHGLVFGDDT DQEAVAQMLD FISSHTFVPI LGIHGGASMI MADKDPTSTF F QFGASIQQ QATVMLKIMQ DYDWHVFSLV TTIFPGYREF ISFVKTTVDN SFVGWDMQNV ITLDTSFEDA KTQVQLKKIH SS VILLYSS KDEAVLILSE ARSLGLTGYD FFWIVPSLVS GNTELIPKEF PSGLISVSYD DWDYSLEARV RDGIGILTTA ASS MLEKFS YIPEAKASCY GQMERPEVPM HTLHPFMVNV TWDGKDLSFT EEGYQVHPRL VVIVLNKDRE WEKVGKWENH TLSL RHAVW PRYKSFSDSE PDDNHLSIVT LEEAPFVIVE DIDPLTETCV RNTVPCRKFV KINNSTNEGM NVKKCCKGFS IDILK KLSR TVKFTYDLYL VTNGKHGKKV NNVWNGMIGE VVYQRAVMAV GSLTINEERS EVVDFSVPFV ETGISVMVSR SNGTVS PSA FLEPFSASVW VMMFVMLLIV SAIAVFVFEY FSPVGYNRNL AKGKAPHGPS FTIGKAIWLL WGLVFNNSVP VQNPKGT TS KIMVSVWAFF AVIFLASYTA NLAAFMIQEE FVDQVTGLSD KKFQRPHDYS PPFRFGTVPN GSTERNIRNN YPYMHQYM T KFNQKGVEDA LVSLKTGKLD AFIYDAAVLN YKAGRDEGCK LVTIGSGYIF ATTGYGIALQ KGSPWKRQID LALLQFVGD GEMEELETLW LTGICHNEKN EVMSSQLDID NMAGVFYMLA AAMALSLITF IWEHLFYWKL RFSFTGTETS QVAPA |
-分子 #3: Glutamate receptor ionotropic, NMDA 2C
分子 | 名称: Glutamate receptor ionotropic, NMDA 2C / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 96.958406 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGTMRLFLLA VLFLFSFARA TGWSHPQFEK GGGSGGGSGG SAWSHPQFEK GALVPRGEQG MTVAVVFSSS GPPQAQFRAR LTPQSFLDL PLEIQPLTVG VNTTNPSSLL TQICGLLGAA HVHGIVFEDN VDTEAVAQIL DFISSQTHVP ILSISGGSAV V LTPKEPGS ...文字列: MGTMRLFLLA VLFLFSFARA TGWSHPQFEK GGGSGGGSGG SAWSHPQFEK GALVPRGEQG MTVAVVFSSS GPPQAQFRAR LTPQSFLDL PLEIQPLTVG VNTTNPSSLL TQICGLLGAA HVHGIVFEDN VDTEAVAQIL DFISSQTHVP ILSISGGSAV V LTPKEPGS AFLQLGVSLE QQLQVLFKVL EEYDWSAFAV ITSLHPGHAL FLEGVRAVAD ASHVSWRLLD VVTLELGPGG PR ARTQRLL RQLDAPVFVA YCSREEAEVL FAEAAQAGLV GPGHVWLVPN LALGSTDAPP ATFPVGLISV VTESWRLSLR QKV RDGVAI LALGAHSYWR QHGTLPAPAG DCRVHPGPVS PAREAFYRHL LNVTWEGRDF SFSPGGYLVQ PTMVVIALNR HRLW EMVGR WEHGVLYMKY PVWPRYSASL QPVVDSRHLT VATLEERPFV IVESPDPGTG GCVPNTVPCR RQSNHTFSSG DVAPY TKLC CKGFCIDILK KLARVVKFSY DLYLVTNGKH GKRVRGVWNG MIGEVYYKRA DMAIGSLTIN EERSEIVDFS VPFVET GIS VMVARSNGTV SPSAFLEPYS PAVWVMMFVM CLTVVAITVF MFEYFSPVSY NQNLTRGKKS GGPAFTIGKS VWLLWAL VF NNSVPIENPR GTTSKIMVLV WAFFAVIFLA SYTANLAAFM IQEQYIDTVS GLSDKKFQRP QDQYPPFRFG TVPNGSTE R NIRSNYRDMH THMVKFNQRS VEDALTSLKM GKLDAFIYDA AVLNYMAGKD EGCKLVTIGS GKVFATTGYG IAMQKDSHW KRAIDLALLQ FLGDGETQKL ETVWLSGICQ NEKNEVMSSK LDIDNMAGVF YMLLVAMGLA LLVFAWEHLV YWKLRHSVPN |
-分子 #4: Nanobody 4
分子 | 名称: Nanobody 4 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 16.549539 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MKYLLPTAAA GLLLLAAQPA MAQVQLQESG GGLVQAGGSL RLSCAASAAA AAAAAAGWYR QAPGKERAAA AAAAAAAAAA AADSVKGRF TISRDNAKNT VYLQMNSLKP EDTAVYYCAA AAAAAAAAAY WGQGTQVTVS SGSGSSRLEE ELRRRLTEHH H HHH |
-分子 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 6 / 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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![]() | 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 mg/mL |
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緩衝液 | pH: 7.5 |
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 / 装置: FEI VITROBOT MARK IV |
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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 K3 BIOQUANTUM (6k x 4k) 平均電子線量: 57.6 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): 2.8000000000000003 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 |
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画像解析
初期モデル | モデルのタイプ: EMDB MAP EMDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 4.24 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cisTEM (ver. 1.0.2) / 使用した粒子像数: 375086 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |