+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7fbs | ||||||
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タイトル | structure of a channel | ||||||
要素 | Sodium channel protein type 5 subunit alpha,Sodium channel protein type 5 subunit alpha,Sodium channel protein type 5 subunit alpha,G protein/GFP fusion protein | ||||||
キーワード | MEMBRANE PROTEIN / ion channel / four-domain | ||||||
機能・相同性 | 機能・相同性情報 voltage-gated sodium channel activity involved in AV node cell action potential / voltage-gated sodium channel activity involved in bundle of His cell action potential / voltage-gated sodium channel activity involved in SA node cell action potential / bundle of His cell action potential / AV node cell action potential / sodium channel complex / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential / response to denervation involved in regulation of muscle adaptation ...voltage-gated sodium channel activity involved in AV node cell action potential / voltage-gated sodium channel activity involved in bundle of His cell action potential / voltage-gated sodium channel activity involved in SA node cell action potential / bundle of His cell action potential / AV node cell action potential / sodium channel complex / SA node cell action potential / AV node cell to bundle of His cell communication / membrane depolarization during SA node cell action potential / response to denervation involved in regulation of muscle adaptation / cardiac ventricle development / regulation of ventricular cardiac muscle cell membrane depolarization / regulation of atrial cardiac muscle cell membrane repolarization / membrane depolarization during atrial cardiac muscle cell action potential / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transport / brainstem development / membrane depolarization during AV node cell action potential / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / membrane depolarization during bundle of His cell action potential / positive regulation of action potential / atrial cardiac muscle cell action potential / membrane depolarization during Purkinje myocyte cell action potential / telencephalon development / regulation of atrial cardiac muscle cell membrane depolarization / membrane depolarization during cardiac muscle cell action potential / positive regulation of sodium ion transport / sodium ion import across plasma membrane / ventricular cardiac muscle cell action potential / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / regulation of cardiac muscle cell contraction / voltage-gated sodium channel complex / membrane depolarization during action potential / voltage-gated sodium channel activity / ankyrin binding / sodium ion transport / positive regulation of heart rate / nitric-oxide synthase binding / fibroblast growth factor binding / regulation of heart rate by cardiac conduction / odontogenesis of dentin-containing tooth / membrane depolarization / intercalated disc / sodium ion transmembrane transport / lateral plasma membrane / neuronal action potential / cardiac muscle contraction / T-tubule / cellular response to calcium ion / regulation of heart rate / bioluminescence / cerebellum development / generation of precursor metabolites and energy / caveola / positive regulation of epithelial cell proliferation / response to organic cyclic compound / sarcolemma / Z disc / scaffold protein binding / transmembrane transporter binding / calmodulin binding / symbiont entry into host cell / protein domain specific binding / axon / viral envelope / ubiquitin protein ligase binding / virion attachment to host cell / protein kinase binding / perinuclear region of cytoplasm / enzyme binding / cell surface / endoplasmic reticulum / membrane / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Rattus norvegicus (ドブネズミ) Recombinant vesicular stomatitis Indiana virus rVSV-G/GFP (ウイルス) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.4 Å | ||||||
データ登録者 | Jiang, D.J. / Catterall, W.A. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Cell / 年: 2021 タイトル: Open-state structure and pore gating mechanism of the cardiac sodium channel. 著者: Daohua Jiang / Richard Banh / Tamer M Gamal El-Din / Lige Tonggu / Michael J Lenaeus / Régis Pomès / Ning Zheng / William A Catterall / 要旨: The heartbeat is initiated by voltage-gated sodium channel Na1.5, which opens rapidly and triggers the cardiac action potential; however, the structural basis for pore opening remains unknown. Here, ...The heartbeat is initiated by voltage-gated sodium channel Na1.5, which opens rapidly and triggers the cardiac action potential; however, the structural basis for pore opening remains unknown. Here, we blocked fast inactivation with a mutation and captured the elusive open-state structure. The fast inactivation gate moves away from its receptor, allowing asymmetric opening of pore-lining S6 segments, which bend and rotate at their intracellular ends to dilate the activation gate to ∼10 Å diameter. Molecular dynamics analyses predict physiological rates of Na conductance. The open-state pore blocker propafenone binds in a high-affinity pose, and drug-access pathways are revealed through the open activation gate and fenestrations. Comparison with mutagenesis results provides a structural map of arrhythmia mutations that target the activation and fast inactivation gates. These results give atomic-level insights into molecular events that underlie generation of the action potential, open-state drug block, and fast inactivation of cardiac sodium channels, which initiate the heartbeat. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7fbs.cif.gz | 230.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7fbs.ent.gz | 179 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7fbs.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7fbs_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7fbs_full_validation.pdf.gz | 1.3 MB | 表示 | |
XML形式データ | 7fbs_validation.xml.gz | 49.1 KB | 表示 | |
CIF形式データ | 7fbs_validation.cif.gz | 71.5 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/fb/7fbs ftp://data.pdbj.org/pub/pdb/validation_reports/fb/7fbs | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 209030.625 Da / 分子数: 1 / 変異: I1487Q,F1488Q,M1489Q / 由来タイプ: 組換発現 由来: (組換発現) Rattus norvegicus (ドブネズミ), (組換発現) Recombinant vesicular stomatitis Indiana virus rVSV-G/GFP (ウイルス) 遺伝子: Scn5a, G, GFP / 発現宿主: Mammalian 1 orthobornavirus (ウイルス) / 参照: UniProt: P15389, UniProt: B7UCZ6 | ||||||||
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#2: 糖 | #3: 化合物 | ChemComp-6OU / [( #4: 化合物 | ChemComp-4Y4 / | #5: 化合物 | 研究の焦点であるリガンドがあるか | Y | |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: sodium channel with four homologous domains / タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT | ||||||||||||
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分子量 | 値: 0.25 MDa / 実験値: NO | ||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 6 | ||||||||||||
試料 | 濃度: 5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. | ||||||||||||
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / Cs: 2.7 mm |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 60 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
電子光学装置 | エネルギーフィルター名称: GIF Quantum ER / エネルギーフィルタースリット幅: 20 eV |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.17.1_3660: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 287306 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT / 空間: REAL | ||||||||||||||||||||||||
拘束条件 |
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