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基本情報
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タイトル | Structure of AMPA receptor GluA2 complex with auxiliary subunit TARP gamma-5 bound to competitive antagonist ZK and antiepileptic drug perampanel (closed state) | |||||||||||||||
![]() | Structure of AMPA receptor GluA2 complex with auxiliary subunit TARP gamma-5 bound to competitive antagonist ZK and antiepileptic drug perampanel (closed state) | |||||||||||||||
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![]() | AMPA receptor / neurotransmission / TARP gamma-5 / perampanel / SIGNALING PROTEIN | |||||||||||||||
機能・相同性 | ![]() neurotransmitter receptor transport, postsynaptic endosome to lysosome / regulation of AMPA receptor activity / neurotransmitter receptor internalization / postsynaptic neurotransmitter receptor diffusion trapping / spine synapse / dendritic spine neck / dendritic spine head / Activation of AMPA receptors / perisynaptic space / transmission of nerve impulse ...neurotransmitter receptor transport, postsynaptic endosome to lysosome / regulation of AMPA receptor activity / neurotransmitter receptor internalization / postsynaptic neurotransmitter receptor diffusion trapping / spine synapse / dendritic spine neck / dendritic spine head / Activation of AMPA receptors / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / channel regulator activity / ligand-gated monoatomic cation channel activity / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / immunoglobulin binding / AMPA glutamate receptor complex / kainate selective glutamate receptor activity / ionotropic glutamate receptor complex / extracellularly glutamate-gated ion channel activity / cellular response to glycine / asymmetric synapse / regulation of receptor recycling / voltage-gated calcium channel activity / Unblocking of NMDA receptors, glutamate binding and activation / positive regulation of synaptic transmission / glutamate receptor binding / extracellular ligand-gated monoatomic ion channel activity / glutamate-gated calcium ion channel activity / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / regulation of synaptic transmission, glutamatergic / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / cytoskeletal protein binding / dendrite cytoplasm / ionotropic glutamate receptor signaling pathway / positive regulation of synaptic transmission, glutamatergic / SNARE binding / dendritic shaft / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / protein tetramerization / postsynaptic density membrane / ionotropic glutamate receptor binding / modulation of chemical synaptic transmission / establishment of protein localization / Schaffer collateral - CA1 synapse / terminal bouton / receptor internalization / cerebral cortex development / synaptic vesicle membrane / synaptic vesicle / presynapse / signaling receptor activity / presynaptic membrane / amyloid-beta binding / growth cone / scaffold protein binding / chemical synaptic transmission / postsynaptic membrane / perikaryon / dendritic spine / postsynaptic density / neuron projection / axon / neuronal cell body / glutamatergic synapse / synapse / dendrite / protein-containing complex binding / protein kinase binding / cell surface / endoplasmic reticulum / protein-containing complex / 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: 2.81 Å | |||||||||||||||
![]() | Gangwar SP / Yen LY / Yelshanskaya MV / Sobolevsky AI | |||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Modulation of GluA2-γ5 synaptic complex desensitization, polyamine block and antiepileptic perampanel inhibition by auxiliary subunit cornichon-2. 著者: Shanti Pal Gangwar / Laura Y Yen / Maria V Yelshanskaya / Aryeh Korman / Drew R Jones / Alexander I Sobolevsky / ![]() 要旨: Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat ...Synaptic complexes of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) with auxiliary subunits mediate most excitatory neurotransmission and can be targeted to treat neuropsychiatric and neurological disorders, including epilepsy. Here we present cryogenic-electron microscopy structures of rat GluA2 AMPAR complexes with inhibitory mouse γ5 and potentiating human cornichon-2 (CNIH2) auxiliary subunits. CNIH2 appears to destabilize the desensitized state of the complex by reducing the separation of the upper lobes in ligand-binding domain dimers. At the same time, CNIH2 stabilizes binding of polyamine spermidine to the selectivity filter of the closed ion channel. Nevertheless, CNIH2, and to a lesser extent γ5, attenuate polyamine block of the open channel and reduce the potency of the antiepileptic drug perampanel that inhibits the synaptic complex allosterically by binding to sites in the ion channel extracellular collar. These findings illustrate the fine-tuning of synaptic complex structure and function in an auxiliary subunit-dependent manner, which is critical for the study of brain region-specific neurotransmission and design of therapeutics for disease treatment. | |||||||||||||||
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マップデータ | ![]() | 259.2 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 22.6 KB 22.6 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 13.7 KB | 表示 | ![]() |
画像 | ![]() | 62.5 KB | ||
Filedesc metadata | ![]() | 7.2 KB | ||
その他 | ![]() ![]() | 255.2 MB 255.2 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 | ![]() 8ss8MC ![]() 8bhfC ![]() 8ss2C ![]() 8ss3C ![]() 8ss4C ![]() 8ss5C ![]() 8ss6C ![]() 8ss7C ![]() 8ss9C ![]() 8ssaC ![]() 8ssbC 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 | Structure of AMPA receptor GluA2 complex with auxiliary subunit TARP gamma-5 bound to competitive antagonist ZK and antiepileptic drug perampanel (closed state) | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.925 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: #1
ファイル | emd_40747_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: #2
ファイル | emd_40747_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 : GluA2-TARP gamma5
全体 | 名称: GluA2-TARP gamma5 |
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要素 |
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-超分子 #1: GluA2-TARP gamma5
超分子 | 名称: GluA2-TARP gamma5 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 詳細: AMPA receptor GluA2 complex with auxiliary subunit TARP gamma-5 bound to competitive antagonist ZK and antiepileptic drug perampanel (closed state) |
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由来(天然) | 生物種: ![]() ![]() |
-分子 #1: Glutamate receptor 2, Voltage-dependent calcium channel gamma-5 s...
分子 | 名称: Glutamate receptor 2, Voltage-dependent calcium channel gamma-5 subunit chimera 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: 114.978859 KDa |
組換発現 | 生物種: ![]() |
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 SACGRKALTL LSSVFAVCGL GLLGIAVSTD YWLYLEEGII LPQNQSTEVK MSLHSGLWRV CFLAGEERG RCFTIEYVMP MNSQMTSEST VNVLKMIRSA TPFPLVSLFF MFIGFILSNI GHIRPHRTIL AFVSGIFFIL S GLSLVVGL VLYISSINDE MLNRTKDAET YFNYKYGWSF AFAAISFLLT ESAGVMSVYL FMKRYTAE UniProtKB: Glutamate receptor 2, Voltage-dependent calcium channel gamma-5 subunit |
-分子 #2: 2-(6'-oxo-1'-phenyl[1',6'-dihydro[2,3'-bipyridine]]-5'-yl)benzonitrile
分子 | 名称: 2-(6'-oxo-1'-phenyl[1',6'-dihydro[2,3'-bipyridine]]-5'-yl)benzonitrile タイプ: ligand / ID: 2 / コピー数: 4 / 式: 6ZP |
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分子量 | 理論値: 349.385 Da |
Chemical component information | ![]() ChemComp-6ZP: |
-分子 #3: {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquino...
分子 | 名称: {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid タイプ: ligand / ID: 3 / コピー数: 4 / 式: ZK1 |
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分子量 | 理論値: 409.254 Da |
Chemical component information | ![]() ChemComp-ZK1: |
-分子 #4: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
分子 | 名称: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / タイプ: ligand / ID: 4 / コピー数: 14 / 式: PCW |
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分子量 | 理論値: 787.121 Da |
Chemical component information | ![]() ChemComp-PCW: |
-分子 #5: SODIUM ION
分子 | 名称: SODIUM ION / タイプ: ligand / ID: 5 / コピー数: 2 |
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分子量 | 理論値: 22.99 Da |
-分子 #6: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 6 / コピー数: 2 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-分子 #7: water
分子 | 名称: water / タイプ: ligand / ID: 7 / コピー数: 11 / 式: HOH |
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分子量 | 理論値: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-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 | 4.5 mg/mL | |||||||||||||||
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緩衝液 | pH: 8 構成要素:
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グリッド | モデル: UltrAuFoil / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 25 sec. / 前処理 - 雰囲気: AIR | |||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV / 詳細: vitrification carried out in nitrogen atmosphere. | |||||||||||||||
詳細 | Protein extracted and purified in detergent micelle. |
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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: FEI FALCON IV (4k x 4k) 平均電子線量: 45.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 100.0 µm / 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 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |