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基本情報
登録情報 | データベース: EMDB / ID: EMD-8652 | |||||||||
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タイトル | Cryo-EM structure of the human ether-a-go-go related K+ channel | |||||||||
![]() | human ether-a-go-go related K+ channel | |||||||||
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![]() | K+ channel / PAS / CNBHD / voltage sensor / selectivity filter / TRANSPORT PROTEIN | |||||||||
機能・相同性 | ![]() inward rectifier potassium channel complex / negative regulation of potassium ion export across plasma membrane / regulation of heart rate by hormone / Phase 3 - rapid repolarisation / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / membrane repolarization during action potential / negative regulation of potassium ion transmembrane transport / membrane repolarization during ventricular cardiac muscle cell action potential / membrane repolarization during cardiac muscle cell action potential / potassium ion export across plasma membrane ...inward rectifier potassium channel complex / negative regulation of potassium ion export across plasma membrane / regulation of heart rate by hormone / Phase 3 - rapid repolarisation / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / membrane repolarization during action potential / negative regulation of potassium ion transmembrane transport / membrane repolarization during ventricular cardiac muscle cell action potential / membrane repolarization during cardiac muscle cell action potential / potassium ion export across plasma membrane / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / C3HC4-type RING finger domain binding / regulation of membrane repolarization / membrane repolarization / positive regulation of potassium ion transmembrane transport / Voltage gated Potassium channels / inward rectifier potassium channel activity / potassium ion homeostasis / membrane depolarization during action potential / ventricular cardiac muscle cell action potential / regulation of potassium ion transmembrane transport / delayed rectifier potassium channel activity / regulation of ventricular cardiac muscle cell membrane repolarization / regulation of heart rate by cardiac conduction / voltage-gated potassium channel activity / potassium ion import across plasma membrane / cardiac muscle contraction / voltage-gated potassium channel complex / potassium ion transmembrane transport / regulation of membrane potential / cellular response to xenobiotic stimulus / scaffold protein binding / transcription cis-regulatory region binding / ubiquitin protein ligase binding / positive regulation of DNA-templated transcription / perinuclear region of cytoplasm / cell surface / protein homodimerization activity / identical protein binding / 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: 4.0 Å | |||||||||
![]() | Wang WW / MacKinnon R | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Cryo-EM Structure of the Open Human Ether-à-go-go-Related K Channel hERG. 著者: Weiwei Wang / Roderick MacKinnon / ![]() 要旨: The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or ...The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or pharmacological inhibition produces Long QT syndrome and the lethal cardiac arrhythmia torsade de pointes. We have determined the molecular structure of hERG to 3.8 Å using cryo-electron microscopy. In this structure, the voltage sensors adopt a depolarized conformation, and the pore is open. The central cavity has an atypically small central volume surrounded by four deep hydrophobic pockets, which may explain hERG's unusual sensitivity to many drugs. A subtle structural feature of the hERG selectivity filter might correlate with its fast inactivation rate, which is key to hERG's role in cardiac action potential repolarization. | |||||||||
履歴 |
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 57 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16.9 KB 16.9 KB | 表示 表示 | ![]() |
画像 | ![]() | 186.6 KB | ||
Filedesc metadata | ![]() | 6.7 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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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 | human ether-a-go-go related K+ channel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X: 0.56563 Å / Y: 0.56563 Å / Z: 0.46445 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
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試料の構成要素
-全体 : human ether-a-go-go related K+ channel hERG
全体 | 名称: human ether-a-go-go related K+ channel hERG |
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要素 |
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-超分子 #1: human ether-a-go-go related K+ channel hERG
超分子 | 名称: human ether-a-go-go related K+ channel hERG / タイプ: organelle_or_cellular_component / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Truncated hERG construct hERGTs (amino acid residues 141-380 and 871-1005 deleted) with S631A mutation |
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由来(天然) | 生物種: ![]() |
-分子 #1: Potassium voltage-gated channel subfamily H member 2
分子 | 名称: Potassium voltage-gated channel subfamily H member 2 タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 88.885664 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MPVRRGHVAP QNTFLDTIIR KFEGQSRKFI IANARVENCA VIYCNDGFCE LCGYSRAEVM QRPCTCDFLH GPRTQRRAAA QIAQALLGA EERKVEIAFY RKDGSCFLCL VDVVPVKNED GAVIMFILNF EVVMEKDMVG SGADVLPEYK LQAPRIHRWT I LHYSPFKA ...文字列: MPVRRGHVAP QNTFLDTIIR KFEGQSRKFI IANARVENCA VIYCNDGFCE LCGYSRAEVM QRPCTCDFLH GPRTQRRAAA QIAQALLGA EERKVEIAFY RKDGSCFLCL VDVVPVKNED GAVIMFILNF EVVMEKDMVG SGADVLPEYK LQAPRIHRWT I LHYSPFKA VWDWLILLLV IYTAVFTPYS AAFLLKETEE GPPATECGYA CQPLAVVDLI VDIMFIVDIL INFRTTYVNA NE EVVSHPG RIAVHYFKGW FLIDMVAAIP FDLLIFGSGS EELIGLLKTA RLLRLVRVAR KLDRYSEYGA AVLFLLMCTF ALI AHWLAC IWYAIGNMEQ PHMDSRIGWL HNLGDQIGKP YNSSGLGGPS IKDKYVTALY FTFSSLTSVG FGNVAPNTNS EKIF SICVM LIGSLMYASI FGNVSAIIQR LYSGTARYHT QMLRVREFIR FHQIPNPLRQ RLEEYFQHAW SYTNGIDMNA VLKGF PECL QADICLHLNR SLLQHCKPFR GATKGCLRAL AMKFKTTHAP PGDTLVHAGD LLTALYFISR GSIEILRGDV VVAILG KND IFGEPLNLYA RPGKSNGDVR ALTYCDLHKI HRDDLLEVLD MYPEFSDHFW SSLEITFNLR DTNMIPGGRQ YQELPRC PA PTPSLLNIPL SSPGRRPRGD VESRLDALQR QLNRLETRLS ADMATVLQLL QRQMTLVPPA YSAVTTPGPG PTSTSPLL P VSPLPTLTLD SLSQVSQFMA CEELPPGAPE LPQEGPTRRL SLPGQLGALT SQPLHRHGSD PGSEASNSLE VLFQ UniProtKB: Potassium voltage-gated channel subfamily H member 2, Potassium voltage-gated channel subfamily H member 2, Potassium voltage-gated channel subfamily H member 2 |
-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 | 6 mg/mL | ||||||||||||||||||||||||
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緩衝液 | pH: 7.4 構成要素:
詳細: pH 7.4, adjusted with NaOH | ||||||||||||||||||||||||
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 400 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: PLASMA CLEANING / 前処理 - 時間: 12 sec. / 前処理 - 雰囲気: AIR / 前処理 - 気圧: 101.325 kPa | ||||||||||||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 98 % / チャンバー内温度: 298 K / 装置: FEI VITROBOT MARK IV / 詳細: one blot: 3 second blot time, 0 blot force. | ||||||||||||||||||||||||
詳細 | A 1 mL peak fraction was collected and concentrated ~3x to obtain the final ~6 mg/mL sample. |
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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: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / デジタル化 - サイズ - 横: 7420 pixel / デジタル化 - サイズ - 縦: 7676 pixel / デジタル化 - 画像ごとのフレーム数: 1-50 / 撮影したグリッド数: 1 / 実像数: 1505 / 平均露光時間: 15.0 sec. / 平均電子線量: 85.0 e/Å2 詳細: 50 0.3-second frames were collected for each movie at a dose rate of ~1.8 e-/A2/frame |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 倍率(補正後): 38461 / 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): 3.5 µm / 最小 デフォーカス(公称値): 0.8 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 |
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画像解析
-原子モデル構築 1
精密化 | 空間: RECIPROCAL / プロトコル: AB INITIO MODEL / 温度因子: 180 / 当てはまり具合の基準: Fourier Shell Correlation |
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得られたモデル | ![]() PDB-5va3: |