+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6uz3 | |||||||||
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タイトル | Cardiac sodium channel | |||||||||
要素 | Sodium channel protein type 5 subunit alpha,Green fluorescent protein | |||||||||
キーワード | METAL TRANSPORT / cardiac sodium channel / ion channel | |||||||||
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 / regulation of ventricular cardiac muscle cell membrane depolarization / cardiac ventricle development / membrane depolarization during atrial cardiac muscle cell action potential / regulation of atrial cardiac muscle cell membrane repolarization / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / regulation of sodium ion transmembrane transport / brainstem development / voltage-gated sodium channel activity involved in cardiac muscle cell action potential / membrane depolarization during AV node 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 / membrane depolarization during action potential / ventricular cardiac muscle cell action potential / sodium ion import across plasma membrane / cardiac muscle cell action potential involved in contraction / regulation of ventricular cardiac muscle cell membrane repolarization / voltage-gated sodium channel complex / regulation of cardiac muscle cell contraction / voltage-gated sodium channel activity / ankyrin binding / positive regulation of heart rate / sodium ion transport / nitric-oxide synthase binding / fibroblast growth factor binding / regulation of heart rate by cardiac conduction / odontogenesis of dentin-containing tooth / membrane depolarization / intercalated disc / neuronal action potential / lateral plasma membrane / sodium ion transmembrane transport / cardiac muscle contraction / positive regulation of epithelial cell proliferation / T-tubule / cellular response to calcium ion / regulation of heart rate / cerebellum development / caveola / response to organic cyclic compound / sarcolemma / Z disc / serine-type endopeptidase inhibitor activity / scaffold protein binding / transmembrane transporter binding / calmodulin binding / protein domain specific binding / axon / ubiquitin protein ligase binding / protein kinase binding / perinuclear region of cytoplasm / enzyme binding / cell surface / endoplasmic reticulum / extracellular space / membrane / metal ion binding / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | Rattus norvegicus (ドブネズミ) Aequorea victoria (オワンクラゲ) | |||||||||
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: 3.5 Å | |||||||||
データ登録者 | Jiang, D. / Shi, H. / Tonggu, L. / Lenaeus, M.J. / Zheng, N. / Catterall, W.A. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Cell / 年: 2020 タイトル: Structure of the Cardiac Sodium Channel. 著者: Daohua Jiang / Hui Shi / Lige Tonggu / Tamer M Gamal El-Din / Michael J Lenaeus / Yan Zhao / Craig Yoshioka / Ning Zheng / William A Catterall / 要旨: Voltage-gated sodium channel Na1.5 generates cardiac action potentials and initiates the heartbeat. Here, we report structures of Na1.5 at 3.2-3.5 Å resolution. Na1.5 is distinguished from other ...Voltage-gated sodium channel Na1.5 generates cardiac action potentials and initiates the heartbeat. Here, we report structures of Na1.5 at 3.2-3.5 Å resolution. Na1.5 is distinguished from other sodium channels by a unique glycosyl moiety and loss of disulfide-bonding capability at the Naβ subunit-interaction sites. The antiarrhythmic drug flecainide specifically targets the central cavity of the pore. The voltage sensors are partially activated, and the fast-inactivation gate is partially closed. Activation of the voltage sensor of Domain III allows binding of the isoleucine-phenylalanine-methionine (IFM) motif to the inactivation-gate receptor. Asp and Ala, in the selectivity motif DEKA, line the walls of the ion-selectivity filter, whereas Glu and Lys are in positions to accept and release Na ions via a charge-delocalization network. Arrhythmia mutation sites undergo large translocations during gating, providing a potential mechanism for pathogenic effects. Our results provide detailed insights into Na1.5 structure, pharmacology, activation, inactivation, ion selectivity, and arrhythmias. | |||||||||
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 | 6uz3.cif.gz | 240.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6uz3.ent.gz | 182.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6uz3.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 | 6uz3_validation.pdf.gz | 1.7 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6uz3_full_validation.pdf.gz | 1.7 MB | 表示 | |
XML形式データ | 6uz3_validation.xml.gz | 54.3 KB | 表示 | |
CIF形式データ | 6uz3_validation.cif.gz | 77.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/uz/6uz3 ftp://data.pdbj.org/pub/pdb/validation_reports/uz/6uz3 | 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
-タンパク質 , 1種, 1分子 A
#1: タンパク質 | 分子量: 209037.781 Da / 分子数: 1 / 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) Aequorea victoria (オワンクラゲ) 遺伝子: Scn5a, GFP / 器官: heart / プラスミド: pEG_BacMam / 細胞株 (発現宿主): HEK293S / 発現宿主: Mammalian 1 orthobornavirus (ウイルス) / 参照: UniProt: P15389, UniProt: P42212 |
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-糖 , 3種, 5分子
#2: 多糖 | #3: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #4: 糖 | |
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-非ポリマー , 2種, 16分子
#5: 化合物 | ChemComp-9Z9 / ( #6: 化合物 | ChemComp-6OU / [( |
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-詳細
研究の焦点であるリガンドがあるか | N |
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-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: cardiac sodium channel apo structure / 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) | 生物種: Rattus norvegicus (ドブネズミ) / 器官: heart | |||||||||||||||
由来(組換発現) | 生物種: Mammalian 1 orthobornavirus (ウイルス) / 株: HEK293 / プラスミド: pEG_BacMam | |||||||||||||||
緩衝液 | pH: 6 | |||||||||||||||
緩衝液成分 |
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試料 | 濃度: 4.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: This sample include channel protein solubilized with GDN detergent. | |||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: UltrAuFoil | |||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K / 詳細: waiting for 20s, blot for 2.5-3.5s before plunging |
-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 詳細: Squares on grids were manually screened before data collection |
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 / 倍率(公称値): 130000 X / 最大 デフォーカス(公称値): 2800 nm / 最小 デフォーカス(公称値): 1200 nm / Calibrated defocus min: 1000 nm / 最大 デフォーカス(補正後): 3000 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER 最高温度: 103 K / 最低温度: 95 K |
撮影 | 平均露光時間: 8 sec. / 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) 撮影したグリッド数: 6 / 実像数: 7400 |
電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 20 eV |
画像スキャン | 動画フレーム数/画像: 40 / 利用したフレーム数/画像: 1-40 |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.15.2_3472: / 分類: 精密化 | ||||||||||||||||||||||||||||||
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EMソフトウェア |
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画像処理 | 詳細: The images were manually inspected. | ||||||||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 2188972 / 詳細: particles were autopicked in relion3 | ||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 106104 / クラス平均像の数: 1 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||
原子モデル構築 | B value: 100 / プロトコル: RIGID BODY FIT / 空間: REAL | ||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 6AGF PDB chain-ID: A | ||||||||||||||||||||||||||||||
拘束条件 |
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