+
データを開く
-
基本情報
登録情報 | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Gly-,PPDA- bound GluN1a-2B-2D NMDAR | |||||||||
![]() | Composite map | |||||||||
![]() |
| |||||||||
![]() | NMDAR / PPDA-bound / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() glycine-gated cation channel activity / regulation of sensory perception of pain / excitatory chemical synaptic transmission / Activated NTRK2 signals through FYN / Synaptic adhesion-like molecules / cellular response to L-glutamate / response to glycine / propylene metabolic process / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport ...glycine-gated cation channel activity / regulation of sensory perception of pain / excitatory chemical synaptic transmission / Activated NTRK2 signals through FYN / Synaptic adhesion-like molecules / cellular response to L-glutamate / response to glycine / propylene metabolic process / negative regulation of dendritic spine maintenance / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / voltage-gated monoatomic cation channel activity / Neurexins and neuroligins / neurotransmitter receptor complex / NMDA selective glutamate receptor complex / ligand-gated sodium channel activity / calcium ion transmembrane import into cytosol / glutamate receptor signaling pathway / glutamate binding / protein heterotetramerization / glycine binding / positive regulation of reactive oxygen species biosynthetic process / positive regulation of calcium ion transport into cytosol / Negative regulation of NMDA receptor-mediated neuronal transmission / startle response / Unblocking of NMDA receptors, glutamate binding and activation / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / Long-term potentiation / monoatomic cation transport / excitatory synapse / positive regulation of excitatory postsynaptic potential / monoatomic ion channel complex / synaptic cleft / glutamate-gated receptor activity / calcium ion homeostasis / MECP2 regulates neuronal receptors and channels / presynaptic active zone membrane / glutamate-gated calcium ion channel activity / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / EPHB-mediated forward signaling / sodium ion transmembrane transport / Ras activation upon Ca2+ influx through NMDA receptor / ionotropic glutamate receptor signaling pathway / positive regulation of synaptic transmission, glutamatergic / hippocampal mossy fiber to CA3 synapse / adult locomotory behavior / regulation of membrane potential / excitatory postsynaptic potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic transmission, glutamatergic / synaptic membrane / postsynaptic density membrane / terminal bouton / brain development / visual learning / calcium ion transmembrane transport / regulation of synaptic plasticity / long-term synaptic potentiation / late endosome / synaptic vesicle / signaling receptor activity / amyloid-beta binding / RAF/MAP kinase cascade / chemical synaptic transmission / dendritic spine / response to ethanol / postsynaptic membrane / cytoskeleton / learning or memory / lysosome / calmodulin binding / neuron projection / postsynaptic density / synapse / dendrite / calcium ion binding / endoplasmic reticulum membrane / protein-containing complex binding / glutamatergic synapse / 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: 3.65 Å | |||||||||
![]() | Hyunook K / Hiro F | |||||||||
資金援助 | ![]()
| |||||||||
![]() | ![]() タイトル: Structural basis for channel gating and blockade in tri-heteromeric GluN1-2B-2D NMDA receptor. 著者: Hyunook Kang / Max Epstein / Tue G Banke / Riley Perszyk / Noriko Simorowski / Srinu Paladugu / Dennis C Liotta / Stephen F Traynelis / Hiro Furukawa / ![]() 要旨: Discrete activation of N-methyl-D-aspartate receptor (NMDAR) subtypes by glutamate and the co-agonist glycine is fundamental to neuroplasticity. A distinct variant, the tri-heteromeric receptor, ...Discrete activation of N-methyl-D-aspartate receptor (NMDAR) subtypes by glutamate and the co-agonist glycine is fundamental to neuroplasticity. A distinct variant, the tri-heteromeric receptor, comprising glycine-binding GluN1 and two types of glutamate-binding GluN2 subunits, exhibits unique pharmacological characteristics, notably enhanced sensitivity to the anti-depressant channel blocker S-(+)-ketamine. Despite its significance, the structural mechanisms underlying ligand gating and channel blockade of tri-heteromeric NMDARs remain poorly understood. Here, we identify and characterize tri-heteromeric GluN1-2B-2D NMDAR in the adult brain, resolving its structures in the activated, inhibited, and S-(+)-ketamine-blocked states. These structures reveal the ligand-dependent conformational dynamics that modulate the tension between the extracellular domain and transmembrane channels, governing channel gating and blockade. Additionally, we demonstrate that the inhibitor (S)-DQP-997-74 selectively decouples linker tension in GluN2D, offering insights into subtype-selective targeting for cognitive modulation. | |||||||||
履歴 |
|
-
構造の表示
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 | ![]() | 229.2 MB | ![]() | |
---|---|---|---|---|
ヘッダ (付随情報) | ![]() ![]() | 28.7 KB 28.7 KB | 表示 表示 | ![]() |
画像 | ![]() | 40.4 KB | ||
Filedesc metadata | ![]() | 8.4 KB | ||
その他 | ![]() ![]() ![]() | 230.4 MB 230.3 MB 230.4 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 | ![]() 9d39MC ![]() 9d37C ![]() 9d38C ![]() 9d3aC ![]() 9d3bC ![]() 9d3cC ![]() 46513 ![]() 46514 ![]() 46515 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 ( |
---|---|
類似構造データ | 類似検索 - 機能・相同性 ![]() |
-
リンク
EMDBのページ | ![]() ![]() |
---|---|
「今月の分子」の関連する項目 |
-
マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Composite 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: 0.827 Å | ||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-追加マップ: ECD local refined map
ファイル | emd_46528_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | ECD local refined map | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-追加マップ: TMD local refined map
ファイル | emd_46528_additional_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | TMD local refined map | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-追加マップ: consensus map
ファイル | emd_46528_additional_3.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | consensus map | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-
試料の構成要素
-全体 : Tri-heteromeric GluN1a-2B-2D NMDAR
全体 | 名称: Tri-heteromeric GluN1a-2B-2D NMDAR |
---|---|
要素 |
|
-超分子 #1: Tri-heteromeric GluN1a-2B-2D NMDAR
超分子 | 名称: Tri-heteromeric GluN1a-2B-2D NMDAR / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 377 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 |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 92.691828 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DPKIVNIGAV LSTRKHEQMF REAVNQANKR HGSWKIQLNA TSVTHKPNAI QMALSVCEDL ISSQVYAILV SHPPTPNDHF TPTPVSYTA GFYRIPVLGL TTRMSIYSDK SIHLSFLRTV PPYSHQSSVW FEMMRVYSWN HIILLVSDDH EGRAAQKRLE T LLEERESK ...文字列: DPKIVNIGAV LSTRKHEQMF REAVNQANKR HGSWKIQLNA TSVTHKPNAI QMALSVCEDL ISSQVYAILV SHPPTPNDHF TPTPVSYTA GFYRIPVLGL TTRMSIYSDK SIHLSFLRTV PPYSHQSSVW FEMMRVYSWN HIILLVSDDH EGRAAQKRLE T LLEERESK AEKVLQFDPG TKNVTALLME AKELEARVII LSASEDDAAT VYRAAAMLNM TGSGYVWLVG EREISGNALR YA PDGILGL QLINGKNESA HISDAVGVVA QAVHELLEKE NITDPPRGCV GNTNIWKTGP LFKRVLMSSK YADGVTGRVE FNE DGDRKF ANYSIMNLQN RKLVQVGIYN GTHVIPNDRK IIWPGGETEK PRGYQMSTRL KIVTIHQEPF VYVKPTLSDG TCKE EFTVN GDPVKKVICT GPNDTSPGSP RHTVPQCCYG FCIDLLIKLA RTMNFTYEVH LVADGKFGTQ ERVNNSNKKE WNGMM GELL SGQADMIVAP LTINNERAQY IEFSKPFKYQ GLTILVKKEI PRSTLDSFMQ PFQSTLWLLV GLSVHVVAVM LYLLDR FSP FGRFKVNSEE EEEDALTLSS AMWFSWGVLL NSGIGEGAPR SFSARILGMV WAGFAMIIVA SYTANLAAFL VLDRPEE RI TGINDPRLRN PSDKFIYATV KQSSVDIYFR RQVELSTMYR HMEKHNYESA AEAIQAVRDN KLHAFIWDSA VLEFEASQ K CDLVTTGELF FRSGFGIGMR KDSPWKQNVS LSILKSHENG FMEDLDKTWV RYQECDSRSN APATLTFENM AGVFMLVAG GIVAGIFLIF IEIAYKRHKD ANGAQ UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-分子 #2: Glutamate receptor ionotropic, NMDA 2B
分子 | 名称: Glutamate receptor ionotropic, NMDA 2B / タイプ: protein_or_peptide / ID: 2 詳細: Twin-strep tag WSHPQFEKGGGSGGGSGGSAWSHPQFEKGALVPRG C-terminal p2A tag GSGATNFSLLKQAGDVEENPG コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 98.622172 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: WSHPQFEKGG GSGGGSGGSA WSHPQFEKGA LVPRGRSQKS PPSIGIAVIL VGTSDEVAIK DAHEKDDFHH LSVVPRVELV AMNETDPKS IITRICDLMS DRKIQGVVFA DDTDQEAIAQ ILDFISAQTL TPILGIHGGS SMIMADKDES SMFFQFGPSI E QQASVMLN ...文字列: WSHPQFEKGG GSGGGSGGSA WSHPQFEKGA LVPRGRSQKS PPSIGIAVIL VGTSDEVAIK DAHEKDDFHH LSVVPRVELV AMNETDPKS IITRICDLMS DRKIQGVVFA DDTDQEAIAQ ILDFISAQTL TPILGIHGGS SMIMADKDES SMFFQFGPSI E QQASVMLN IMEEYDWYIF SIVTTYFPGY QDFVNKIRST IENSFVGWEL EEVLLLDMSL DDGDSKIQNQ LKKLQSPIIL LY CTKEEAT YIFEVANSVG LTGYGYTWIV PSLVAGDTDT VPAEFPTGLI SVSYDEWDYG LPARVRDGIA IITTAASDML SEH SFIPEP KSSCYNTHEK RIYQSNMLNR YLINVTFEGR NLSFSEDGYQ MHPKLVIILL NKERKWERVG KWKDKSLQMK YYVW PRMCP ETEEQEDDHL SIVTLEEAPF VIVESVDPLS GTCMRNTVPC QKRIVTENKT DEEPGYIKKC CKGFCIDILK KISKS VKFT YDLYLVTNGK HGKKINGTWN GMIGEVVMKR AYMAVGSLTI NEERSEVVDF SVPFIETGIS VMVSRSNGTV SPSAFL EPF SADVWVMMFV MLLIVSAVAV FVFEYFSPVG YNRSLADGRE PGGPSFTIGK AIWLLWGLVF NNSVPVQNPK GTTSKIM VS VWAFFAVIFL ASYTANLAAF MIQEEYVDQV SGLSDKKFQR PNDFSPPFRF GTVPNGSTER NIRNNYAEMH AYMGKFNQ R GVDDALLSLK TGKLDAFIYD AAVLNYMAGR DEGCKLVTIG SGKVFASTGY GIAIQKDSGW KRQVDLAILQ LFGDGEMEE LEALWLTGIC HNEKNEVMSS QLDIDNMAGV FYMLGAAMAL SLITFISEHL FYWQFRHSFM GGPGSGATNF SLLKQAGDVE ENPG UniProtKB: Glutamate receptor ionotropic, NMDA 2B |
-分子 #3: Glutamate receptor ionotropic, NMDA 2D
分子 | 名称: Glutamate receptor ionotropic, NMDA 2D / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 94.120609 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: FPEEAPGPGG AGGPGGGLGG ARPLNVALVF SGPAYAAEAA RLGPAVAAAV RSPGLDVRPV ALVLNGSDPR SLVLQLCDLL SGLRVHGVV FEDDSRAPAV APILDFLSAQ TSLPIVAVHG GAALVLTPKE KGSTFLQLGS STEQQLQVIF EVLEEYDWTS F VAVTTRAP ...文字列: FPEEAPGPGG AGGPGGGLGG ARPLNVALVF SGPAYAAEAA RLGPAVAAAV RSPGLDVRPV ALVLNGSDPR SLVLQLCDLL SGLRVHGVV FEDDSRAPAV APILDFLSAQ TSLPIVAVHG GAALVLTPKE KGSTFLQLGS STEQQLQVIF EVLEEYDWTS F VAVTTRAP GHRAFLSYIE VLTDGSLVGW EHRGALTLDP GAGEAVLSAQ LRSVSAQIRL LFCAREEAEP VFRAAEEAGL TG SGYVWFM VGPQLAGGGG SGAPGEPPLL PGGAPLPAGL FAVRSAGWRD DLARRVAAGV AVVARGAQAL LRDYGFLPEL GHD CRAQNR THRGESLHRY FMNITWDNRD YSFNEDGFLV NPSLVVISLT RDRTWEVVGS WEQQTLRLKY PLWSRYGRFL QPVD DTQHL TVATLEERPF VIVEPADPIS GTCIRDSVPC RSQLNRTHSP PPDAPRPEKR CCKGFCIDIL KRLAHTIGFS YDLYL VTNG KHGKKIDGVW NGMIGEVFYQ RADMAIGSLT INEERSEIVD FSVPFVETGI SVMVARSNGT VSPSAFLEPY SPAVWV MMF VMCLTVVAVT VFIFEYLSPV GYNRSLATGK RPGGSTFTIG KSIWLLWALV FNNSVPVENP RGTTSKIMVL VWAFFAV IF LASYTANLAA FMIQEEYVDT VSGLSDRKFQ RPQEQYPPLK FGTVPNGSTE KNIRSNYPDM HSYMVRYNQP RVEEALTQ L KAGKLDAFIY DAAVLNYMAR KDEGCKLVTI GSGKVFATTG YGIALHKGSR WKRPIDLALL QFLGDDEIEM LERLWLSGI CHNDKIEVMS SKLDIDNMAG VFYMLLVAMG LSLLVFAWEH LVYWRLRHCL GPTETSQVAP A 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 |
---|---|
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: 3 / 式: NAG |
---|---|
分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-分子 #6: (2S,3R)-1-(phenanthren-2-ylcarbonyl)piperazine-2,3-dicarboxylic acid
分子 | 名称: (2S,3R)-1-(phenanthren-2-ylcarbonyl)piperazine-2,3-dicarboxylic acid タイプ: ligand / ID: 6 / コピー数: 2 / 式: 2JL |
---|---|
分子量 | 理論値: 378.378 Da |
Chemical component information | ![]() ChemComp-2JL: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
![]() | 単粒子再構成法 |
試料の集合状態 | particle |
-
試料調製
濃度 | 2 mg/mL |
---|---|
緩衝液 | pH: 7.5 |
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 278 K |
-
電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
特殊光学系 | エネルギーフィルター - 名称: GIF Bioquantum / エネルギーフィルター - スリット幅: 14 eV |
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: 59.1 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): 2.4 µm / 最小 デフォーカス(公称値): 1.0 µm |
試料ステージ | ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
+
画像解析
-原子モデル構築 1
初期モデル |
| ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
精密化 | 空間: REAL / プロトコル: RIGID BODY FIT | ||||||||||
得られたモデル | ![]() PDB-9d39: |