+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-7961 | ||||||||||||
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タイトル | Open state GluA2 in complex with STZ and blocked by NASPM, after micelle signal subtraction | ||||||||||||
マップデータ | TMD-directed refinement, micelle signal subtracted | ||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 LGI-ADAM interactions / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / Presynaptic depolarization and calcium channel opening / cerebellar mossy fiber / neurotransmitter receptor transport, postsynaptic endosome to lysosome / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / membrane hyperpolarization ...LGI-ADAM interactions / eye blink reflex / positive regulation of protein localization to basolateral plasma membrane / Presynaptic depolarization and calcium channel opening / cerebellar mossy fiber / neurotransmitter receptor transport, postsynaptic endosome to lysosome / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / membrane hyperpolarization / Trafficking of AMPA receptors / postsynaptic neurotransmitter receptor diffusion trapping / protein targeting to membrane / neurotransmitter receptor localization to postsynaptic specialization membrane / neuromuscular junction development / spine synapse / dendritic spine neck / dendritic spine head / Activation of AMPA receptors / voltage-gated calcium channel complex / response to lithium ion / perisynaptic space / cellular response to glycine / transmission of nerve impulse / AMPA glutamate receptor activity / Trafficking of GluR2-containing AMPA receptors / 脱分極 / immunoglobulin binding / AMPA glutamate receptor complex / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / asymmetric synapse / regulation of receptor recycling / Unblocking of NMDA receptors, glutamate binding and activation / voltage-gated calcium channel activity / glutamate receptor binding / positive regulation of synaptic transmission / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / regulation of synaptic transmission, glutamatergic / cellular response to brain-derived neurotrophic factor stimulus / somatodendritic compartment / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / ionotropic glutamate receptor binding / hippocampal mossy fiber to CA3 synapse / ionotropic glutamate receptor signaling pathway / dendrite cytoplasm / cytoskeletal protein binding / positive regulation of synaptic transmission, glutamatergic / SNARE binding / dendritic shaft / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / postsynaptic density membrane / protein tetramerization / modulation of chemical synaptic transmission / Schaffer collateral - CA1 synapse / establishment of protein localization / terminal bouton / receptor internalization / synaptic vesicle membrane / cerebral cortex development / response to calcium ion / endocytic vesicle membrane / シナプス小胞 / presynapse / signaling receptor activity / presynaptic membrane / amyloid-beta binding / 成長円錐 / perikaryon / chemical synaptic transmission / postsynaptic membrane / scaffold protein binding / 樹状突起スパイン / postsynaptic density / neuron projection / 神経繊維 / 樹状突起 / neuronal cell body / glutamatergic synapse / シナプス / protein-containing complex binding / endoplasmic reticulum membrane / protein kinase binding / 細胞膜 / 小胞体 / protein-containing complex / 生体膜 / identical protein binding / 細胞膜 類似検索 - 分子機能 | ||||||||||||
生物種 | Rattus norvegicus (ドブネズミ) / Homo sapiens (ヒト) | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.2 Å | ||||||||||||
データ登録者 | Twomey EC / Yelshanskaya MV / Vassilevski AA / Sobolevsky AI | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Neuron / 年: 2018 タイトル: Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors. 著者: Edward C Twomey / Maria V Yelshanskaya / Alexander A Vassilevski / Alexander I Sobolevsky / 要旨: AMPA receptors mediate fast excitatory neurotransmission and are critical for CNS development and function. Calcium-permeable subsets of AMPA receptors are strongly implicated in acute and chronic ...AMPA receptors mediate fast excitatory neurotransmission and are critical for CNS development and function. Calcium-permeable subsets of AMPA receptors are strongly implicated in acute and chronic neurological disorders. However, despite the clinical importance, the therapeutic landscape for specifically targeting them, and not the calcium-impermeable AMPA receptors, remains largely undeveloped. To address this problem, we used cryo-electron microscopy and electrophysiology to investigate the mechanisms by which small-molecule blockers selectively inhibit ion channel conductance in calcium-permeable AMPA receptors. We determined the structures of calcium-permeable GluA2 AMPA receptor complexes with the auxiliary subunit stargazin bound to channel blockers, including the orb weaver spider toxin AgTx-636, the spider toxin analog NASPM, and the adamantane derivative IEM-1460. Our structures provide insights into the architecture of the blocker binding site and the mechanism of trapping, which are critical for development of small molecules that specifically target calcium-permeable AMPA receptors. | ||||||||||||
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_7961.map.gz | 9.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-7961-v30.xml emd-7961.xml | 15.5 KB 15.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_7961.png | 295.3 KB | ||
その他 | emd_7961_additional.map.gz | 6.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-7961 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7961 | HTTPS FTP |
-関連構造データ
-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_7961.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | TMD-directed refinement, micelle signal subtracted | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.08 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: Full map, micelle signal subtracted
ファイル | emd_7961_additional.map | ||||||||||||
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注釈 | Full map, micelle signal subtracted | ||||||||||||
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 : Open state GluA2 in complex with STZ and blocked by NASPM, after ...
全体 | 名称: Open state GluA2 in complex with STZ and blocked by NASPM, after micelle signal subtraction |
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要素 |
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-超分子 #1: Open state GluA2 in complex with STZ and blocked by NASPM, after ...
超分子 | 名称: Open state GluA2 in complex with STZ and blocked by NASPM, after micelle signal subtraction タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 詳細: The full-map (non-TMD-directed) is included as a supplemental file |
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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: Homo sapiens (ヒト) / 組換細胞: HEK293 gnti- |
-分子 #1: Glutamate receptor 2,Voltage-dependent calcium channel gamma-2 subunit
分子 | 名称: Glutamate receptor 2,Voltage-dependent calcium channel gamma-2 subunit 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: Homo sapiens (ヒト) |
分子量 | 理論値: 115.178531 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: NSIQIGGLFP RGADQEYSAF RVGMVQFSTS EFRLTPHIDN LEVANSFAVT NAFCSQFSRG VYAIFGFYDK KSVNTITSFC GTLHVSFIT PSFPTDGTHP FVIQMRPDLK GALLSLIEYY QWDKFAYLYD SDRGLSTLQA VLDSAAEKKW QVTAINVGNI N NDKKDETY ...文字列: NSIQIGGLFP RGADQEYSAF RVGMVQFSTS EFRLTPHIDN LEVANSFAVT NAFCSQFSRG VYAIFGFYDK KSVNTITSFC GTLHVSFIT PSFPTDGTHP FVIQMRPDLK GALLSLIEYY QWDKFAYLYD SDRGLSTLQA VLDSAAEKKW QVTAINVGNI N NDKKDETY RSLFQDLELK KERRVILDCE RDKVNDIVDQ VITIGKHVKG YHYIIANLGF TDGDLLKIQF GGAEVSGFQI VD YDDSLVS KFIERWSTLE EKEYPGAHTA TIKYTSALTY DAVQVMTEAF RNLRKQRIEI SRRGNAGDCL ANPAVPWGQG VEI ERALKQ VQVEGLSGNI KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVLTED DTSGLEQKTV VVTTILESPY VMMK KNHEM LEGNERYEGY CVDLAAEIAK HCGFKYKLTI VGDGKYGARD ADTKIWNGMV GELVYGKADI AIAPLTITLV REEVI DFSK PFMSLGISIM IKKPQKSKPG VFSFLDPLAY EIWMCIVFAY IGVSVVLFLV SRFSPYEWHT EEFEDGRETQ SSESTN EFG IFNSLWFSLG AFMQQGCDIS PRSLSGRIVG GVWWFFTLII ISSYTANLAA FLTVERMVSP IESAEDLSKQ TEIAYGT LD SGSTKEFFRR SKIAVFDKMW TYMRSAEPSV FVRTTAEGVA RVRKSKGKYA YLLESTMNEY IEQRKPCDTM KVGGNLDS K GYGIATPKGS SLGTPVNLAV LKLSEQGVLD KLKNKWWYDK GECGAKDSGS KEKTSALSLS NVAGVFYILV GGLGLAMLV ALIEFCYKSR AEAKRMKGTG LFDRGVQMLL TTVGAFAAFS LMTIAVGTDY WLYSRGVCKT KSVSEDETSK KNEEVMTHSG LWRTCCLEG NFKGLCKQID HFPEDADYEA DTAEYFLRAV RASSIFPILS VILLFMGGLC IAASEFYKTR HNIILSAGIF F VSAGLSNI IGIIVYISAN AGDPSKSDSK KNSYSYGWSF YFGALSFIIA EMVGVLAVHM FIDRHKQLTG GAE |
-分子 #2: GLUTAMIC ACID
分子 | 名称: GLUTAMIC ACID / タイプ: ligand / ID: 2 / 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 #3: CYCLOTHIAZIDE
分子 | 名称: CYCLOTHIAZIDE / タイプ: ligand / ID: 3 / コピー数: 4 / 式: CYZ |
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分子量 | 理論値: 389.878 Da |
Chemical component information | ChemComp-CYZ: |
-分子 #4: N-[3-({4-[(3-aminopropyl)amino]butyl}amino)propyl]-2-(naphthalen-...
分子 | 名称: N-[3-({4-[(3-aminopropyl)amino]butyl}amino)propyl]-2-(naphthalen-1-yl)acetamide タイプ: ligand / ID: 4 / コピー数: 1 / 式: GYY |
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分子量 | 理論値: 370.532 Da |
Chemical component information | ChemComp-GYY: |
-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
濃度 | 4 mg/mL |
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緩衝液 | pH: 8 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 295 K / 装置: FEI VITROBOT MARK IV |
詳細 | Open state GluA2 in complex with STZ and blocked by NASPM, after micelle signal subtraction |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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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: SPOT SCAN / 撮影モード: BRIGHT FIELDBright-field microscopy |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 平均露光時間: 8.0 sec. / 平均電子線量: 55.0 e/Å2 |
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: PDB ENTRY PDBモデル - PDB ID: 詳細: Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin |
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初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |
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: 4.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 詳細: Full map (supplemental file) is 4.4 angstrom. / 使用した粒子像数: 39835 |
-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-6dm1: |