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基本情報
登録情報 | ![]() | |||||||||||||||
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タイトル | Open state of kainate receptor GluK2 in complex with agonist glutamate and positive allosteric modulator BPAM344 bound to two concanavalin A dimers. Composite map. | |||||||||||||||
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![]() | kainate receptor / GluK2 / positive allosteric modulator / BPAM344 / open / concanavalin A / ConA / glutamate / MEMBRANE PROTEIN | |||||||||||||||
機能・相同性 | ![]() mossy fiber rosette / detection of cold stimulus involved in thermoception / Activation of Na-permeable kainate receptors / kainate selective glutamate receptor complex / Activation of Ca-permeable Kainate Receptor / negative regulation of synaptic transmission, glutamatergic / D-glucose binding / regulation of short-term neuronal synaptic plasticity / inhibitory postsynaptic potential / glutamate receptor activity ...mossy fiber rosette / detection of cold stimulus involved in thermoception / Activation of Na-permeable kainate receptors / kainate selective glutamate receptor complex / Activation of Ca-permeable Kainate Receptor / negative regulation of synaptic transmission, glutamatergic / D-glucose binding / regulation of short-term neuronal synaptic plasticity / inhibitory postsynaptic potential / glutamate receptor activity / ubiquitin conjugating enzyme binding / receptor clustering / modulation of excitatory postsynaptic potential / D-mannose binding / regulation of JNK cascade / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / neuronal action potential / behavioral fear response / positive regulation of synaptic transmission / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / presynaptic modulation of chemical synaptic transmission / dendrite cytoplasm / hippocampal mossy fiber to CA3 synapse / regulation of membrane potential / SNARE binding / excitatory postsynaptic potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic transmission, glutamatergic / PDZ domain binding / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / modulation of chemical synaptic transmission / terminal bouton / intracellular calcium ion homeostasis / vasodilation / positive regulation of neuron apoptotic process / presynaptic membrane / manganese ion binding / scaffold protein binding / chemical synaptic transmission / postsynaptic membrane / perikaryon / neuron apoptotic process / negative regulation of neuron apoptotic process / postsynaptic density / axon / neuronal cell body / glutamatergic synapse / ubiquitin protein ligase binding / synapse / dendrite / calcium ion binding / identical protein binding / membrane / plasma membrane 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: 4.29 Å | |||||||||||||||
![]() | Nadezhdin KD / Gangwar SP / Sobolevsky AI | |||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Kainate receptor channel opening and gating mechanism. 著者: Shanti Pal Gangwar / Maria V Yelshanskaya / Kirill D Nadezhdin / Laura Y Yen / Thomas P Newton / Muhammed Aktolun / Maria G Kurnikova / Alexander I Sobolevsky / ![]() 要旨: Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and ...Kainate receptors, a subclass of ionotropic glutamate receptors, are tetrameric ligand-gated ion channels that mediate excitatory neurotransmission. Kainate receptors modulate neuronal circuits and synaptic plasticity during the development and function of the central nervous system and are implicated in various neurological and psychiatric diseases, including epilepsy, depression, schizophrenia, anxiety and autism. Although structures of kainate receptor domains and subunit assemblies are available, the mechanism of kainate receptor gating remains poorly understood. Here we present cryo-electron microscopy structures of the kainate receptor GluK2 in the presence of the agonist glutamate and the positive allosteric modulators lectin concanavalin A and BPAM344. Concanavalin A and BPAM344 inhibit kainate receptor desensitization and prolong activation by acting as a spacer between the amino-terminal and ligand-binding domains and a stabilizer of the ligand-binding domain dimer interface, respectively. Channel opening involves the kinking of all four pore-forming M3 helices. Our structures reveal the molecular basis of kainate receptor gating, which could guide the development of drugs for treatment of neurological disorders. | |||||||||||||||
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-EMDBアーカイブ
マップデータ | ![]() | 55.9 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 19.1 KB 19.1 KB | 表示 表示 | ![]() |
画像 | ![]() | 122.7 KB | ||
Filedesc metadata | ![]() | 7.8 KB | ||
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 | ![]() 9b36MC ![]() 9b33C ![]() 9b34C ![]() 9b35C ![]() 9b37C ![]() 9b38C ![]() 9b39C 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: 1.3487 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
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試料の構成要素
-全体 : full-length rat GluK2 tetramer in complex with two concanavalin A...
全体 | 名称: full-length rat GluK2 tetramer in complex with two concanavalin A dimers |
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要素 |
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-超分子 #1: full-length rat GluK2 tetramer in complex with two concanavalin A...
超分子 | 名称: full-length rat GluK2 tetramer in complex with two concanavalin A dimers 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: 510 KDa |
-分子 #1: Glutamate receptor ionotropic, kainate 2
分子 | 名称: Glutamate receptor ionotropic, kainate 2 / タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 102.976586 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MKIISPVLSN LVFSRSIKVL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA VNTINRNRTL LPNTTLTYDT QKINLYDSF EASKKACDQL SLGVAAIFGP SHSSSANAVQ SICNALGVPH IQTRWKHQVS DNKDSFYVSL YPDFSSLSRA I LDLVQFFK ...文字列: MKIISPVLSN LVFSRSIKVL LCLLWIGYSQ GTTHVLRFGG IFEYVESGPM GAEELAFRFA VNTINRNRTL LPNTTLTYDT QKINLYDSF EASKKACDQL SLGVAAIFGP SHSSSANAVQ SICNALGVPH IQTRWKHQVS DNKDSFYVSL YPDFSSLSRA I LDLVQFFK WKTVTVVYDD STGLIRLQEL IKAPSRYNLR LKIRQLPADT KDAKPLLKEM KRGKEFHVIF DCSHEMAAGI LK QALAMGM MTEYYHYIFT TLDLFALDVE PYRYSGVNMT GFRILNTENT QVSSIIEKWS MERLQAPPKP DSGLLDGFMT TDA ALMYDA VHVVSVAVQQ FPQMTVSSLQ CNRHKPWRFG TRFMSLIKEA HWEGLTGRIT FNKTNGLRTD FDLDVISLKE EGLE KIGTW DPASGLNMTE SQKGKPANIT DSLSNRSLIV TTILEEPYVL FKKSDKPLYG NDRFEGYCID LLRELSTILG FTYEI RLVE DGKYGAQDDV NGQWNGMVRE LIDHKADLAV APLAITYVRE KVIDFSKPFM TLGISILYRK PNGTNPGVFS FLNPLS PDI WMYVLLACLG VSCVLFVIAR FSPYEWYNPH PCNPDSDVVE NNFTLLNSFW FGVGALMQQG SELMPKALST RIVGGIW WF FTLIIISSYT ANLAAFLTVE RMESPIDSAD DLAKQTKIEY GAVEDGATMT FFKKSKISTY DKMWAFMSSR RQSVLVKS N EEGIQRVLTS DYAFLMESTT IEFVTQRNCN LTQIGGLIDS KGYGVGTPMG SPYRDKITIA ILQLQEEGKL HMMKEKWWR GNGCPEEESK EASALGVQNI GGIFIVLAAG LVLSVFVAVG EFLYKSKKNA QLEKRSFCSA MVEELRMSLK CQRRLKHKPQ APVIVKTEE VINMHTFNDR RLPGKETMAL VPR UniProtKB: Glutamate receptor ionotropic, kainate 2 |
-分子 #2: Concanavalin A
分子 | 名称: Concanavalin A / タイプ: protein_or_peptide / ID: 2 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 25.622385 KDa |
配列 | 文字列: ADTIVAVELD TYPNTDIGDP SYPHIGIDIK SVRSKKTAKW NMQNGKVGTA HIIYNSVDKR LSAVVSYPNA DSATVSYDVD LDNVLPEWV RVGLSASTGL YKETNTILSW SFTSKLKSNS THETNALHFM FNQFSKDQKD LILQGDATTG TDGNLELTRV S SNGSPQGS ...文字列: ADTIVAVELD TYPNTDIGDP SYPHIGIDIK SVRSKKTAKW NMQNGKVGTA HIIYNSVDKR LSAVVSYPNA DSATVSYDVD LDNVLPEWV RVGLSASTGL YKETNTILSW SFTSKLKSNS THETNALHFM FNQFSKDQKD LILQGDATTG TDGNLELTRV S SNGSPQGS SVGRALFYAP VHIWESSAVV ASFEATFTFL IKSPDSHPAD GIAFFISNID SSIPSGSTGR LLGLFPDAN UniProtKB: Concanavalin V |
-分子 #10: 4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-...
分子 | 名称: 4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide タイプ: ligand / ID: 10 / コピー数: 4 / 式: 2J9 |
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分子量 | 理論値: 242.27 Da |
Chemical component information | ![]() ChemComp-2J9: |
-分子 #11: GLUTAMIC ACID
分子 | 名称: GLUTAMIC ACID / タイプ: ligand / ID: 11 / コピー数: 4 / 式: GLU |
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分子量 | 理論値: 147.129 Da |
Chemical component information | ![]() ChemComp-GLU: |
-分子 #12: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
分子 | 名称: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate タイプ: ligand / ID: 12 / コピー数: 14 / 式: POV |
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分子量 | 理論値: 760.076 Da |
Chemical component information | ![]() ChemComp-POV: |
-分子 #13: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 13 / コピー数: 8 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-分子 #14: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 14 / コピー数: 4 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-分子 #15: CALCIUM ION
分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 15 / コピー数: 4 / 式: CA |
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分子量 | 理論値: 40.078 Da |
-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
緩衝液 | pH: 8 構成要素:
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グリッド | モデル: UltrAuFoil R1.2/1.3 / 材質: GOLD / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY | ||||||||||||||||||||||||
凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / デジタル化 - サイズ - 横: 5760 pixel / デジタル化 - サイズ - 縦: 4092 pixel / 撮影したグリッド数: 5 / 実像数: 22990 / 平均露光時間: 2.5 sec. / 平均電子線量: 58.0 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 / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
精密化 | 空間: REAL |
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得られたモデル | ![]() PDB-9b36: |