+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-31959 | |||||||||
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タイトル | Human N-type voltage gated calcium channel CaV2.2-alpha2/delta1-beta1 complex, bound to ziconotide | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / positive regulation of muscle contraction / membrane depolarization during bundle of His cell action potential / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / host cell presynaptic membrane ...regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / positive regulation of muscle contraction / membrane depolarization during bundle of His cell action potential / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / host cell presynaptic membrane / cardiac muscle cell action potential involved in contraction / NCAM1 interactions / regulation of ventricular cardiac muscle cell membrane repolarization / calcium ion transport into cytosol / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / ion channel inhibitor activity / neuromuscular junction development / calcium ion import across plasma membrane / Phase 0 - rapid depolarisation / neuronal dense core vesicle / regulation of heart rate by cardiac conduction / response to amyloid-beta / regulation of calcium ion transport / calcium channel regulator activity / voltage-gated calcium channel activity / T-tubule / sarcoplasmic reticulum / calcium ion transmembrane transport / modulation of chemical synaptic transmission / cellular response to amyloid-beta / calcium ion transport / amyloid-beta binding / toxin activity / chemical synaptic transmission / neuronal cell body / calcium ion binding / synapse / extracellular exosome / extracellular region / ATP binding / metal ion binding / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Conus magus (ヤキイモ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.0 Å | |||||||||
データ登録者 | Dong Y / Gao Y / Wang Y / Zhao Y | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Cell Rep / 年: 2021 タイトル: Closed-state inactivation and pore-blocker modulation mechanisms of human Ca2.2. 著者: Yanli Dong / Yiwei Gao / Shuai Xu / Yuhang Wang / Zhuoya Yu / Yue Li / Bin Li / Tian Yuan / Bei Yang / Xuejun Cai Zhang / Daohua Jiang / Zhuo Huang / Yan Zhao / 要旨: N-type voltage-gated calcium (Ca) channels mediate Ca influx at presynaptic terminals in response to action potentials and play vital roles in synaptogenesis, release of neurotransmitters, and ...N-type voltage-gated calcium (Ca) channels mediate Ca influx at presynaptic terminals in response to action potentials and play vital roles in synaptogenesis, release of neurotransmitters, and nociceptive transmission. Here, we elucidate a cryo-electron microscopy (cryo-EM) structure of the human Ca2.2 complex in apo, ziconotide-bound, and two Ca2.2-specific pore blockers-bound states. The second voltage-sensing domain (VSD) is captured in a resting-state conformation, trapped by a phosphatidylinositol 4,5-bisphosphate (PIP) molecule, which is distinct from the other three VSDs of Ca2.2, as well as activated VSDs observed in previous structures of Ca channels. This structure reveals the molecular basis for the unique inactivation process of Ca2.2 channels, in which the intracellular gate formed by S6 helices is closed and a W-helix from the domain II-III linker stabilizes closed-state inactivation. The structures of this inactivated, drug-bound complex lay a solid foundation for developing new state-dependent blockers for treatment of chronic pain. | |||||||||
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_31959.map.gz | 118.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-31959-v30.xml emd-31959.xml | 18.7 KB 18.7 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_31959.png | 113.3 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-31959 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31959 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_31959_validation.pdf.gz | 447.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_31959_full_validation.pdf.gz | 446.8 KB | 表示 | |
XML形式データ | emd_31959_validation.xml.gz | 6.7 KB | 表示 | |
CIF形式データ | emd_31959_validation.cif.gz | 7.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31959 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31959 | 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_31959.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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: 1.04 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
-試料の構成要素
+全体 : CaV2.2-alpha2delta1-beta1 complex
+超分子 #1: CaV2.2-alpha2delta1-beta1 complex
+分子 #1: Voltage-dependent N-type calcium channel subunit alpha-1B
+分子 #2: Omega-conotoxin MVIIA
+分子 #3: Voltage-dependent L-type calcium channel subunit beta-1
+分子 #4: Voltage-dependent calcium channel subunit alpha-2/delta-1
+分子 #7: HEXADECANE
+分子 #8: CHOLESTEROL HEMISUCCINATE
+分子 #9: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tr...
+分子 #10: CALCIUM ION
+分子 #11: 2-acetamido-2-deoxy-beta-D-glucopyranose
-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
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-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 K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 9.6 e/Å2 |
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: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |