+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-20949 | |||||||||
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タイトル | Cardiac sodium channel with flecainide | |||||||||
マップデータ | CryoEM map for a drug binding structure | |||||||||
試料 |
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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 / T-tubule / cellular response to calcium ion / regulation of heart rate / bioluminescence / cerebellum development / positive regulation of epithelial cell proliferation / generation of precursor metabolites and energy / caveola / response to organic cyclic compound / sarcolemma / Z disc / 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 / membrane / 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 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.24 Å | |||||||||
データ登録者 | Jiang D / Shi H / Tonggu L / Lenaeus MJ / Zheng N / Catterall WA | |||||||||
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 | 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_20949.map.gz | 59.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-20949-v30.xml emd-20949.xml | 19.2 KB 19.2 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_20949_fsc.xml | 7.1 KB | 表示 | FSCデータファイル |
画像 | emd_20949.png | 63.2 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-20949 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20949 | 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_20949.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | CryoEM map for a drug binding structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.056 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 : cardiac sodium channel complex with flecainide
全体 | 名称: cardiac sodium channel complex with flecainide |
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要素 |
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-超分子 #1: cardiac sodium channel complex with flecainide
超分子 | 名称: cardiac sodium channel complex with flecainide / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) / 器官: heart |
組換発現 | 生物種: Mammalian 1 orthobornavirus (ウイルス) / 組換株: HEK293 / 組換プラスミド: pEG_BacMam |
分子量 | 理論値: 250 KDa |
-分子 #1: Sodium channel protein type 5 subunit alpha,Green fluorescent protein
分子 | 名称: Sodium channel protein type 5 subunit alpha,Green fluorescent protein 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: Aequorea victoria (オワンクラゲ) / 器官: HEART |
分子量 | 理論値: 209.037781 KDa |
組換発現 | 生物種: Mammalian 1 orthobornavirus (ウイルス) |
配列 | 文字列: MANLLLPRGT SSFRRFTRES LAAIEKRMAE KQARGGSATS QESREGLQEE EAPRPQLDLQ ASKKLPDLYG NPPRELIGEP LEDLDPFYS TQKTFIVLNK GKTIFRFSAT NALYVLSPFH PVRRAAVKIL VHSLFSMLIM CTILTNCVFM AQHDPPPWTK Y VEYTFTAI ...文字列: MANLLLPRGT SSFRRFTRES LAAIEKRMAE KQARGGSATS QESREGLQEE EAPRPQLDLQ ASKKLPDLYG NPPRELIGEP LEDLDPFYS TQKTFIVLNK GKTIFRFSAT NALYVLSPFH PVRRAAVKIL VHSLFSMLIM CTILTNCVFM AQHDPPPWTK Y VEYTFTAI YTFESLVKIL ARGFCLHAFT FLRDPWNWLD FSVIVMAYTT EFVDLGNVSA LRTFRVLRAL KTISVISGLK TI VGALIQS VKKLADVMVL TVFCLSVFAL IGLQLFMGNL RHKCVRNFTE LNGTNGSVEA DGLVWNSLDV YLNDPANYLL KNG TTDVLL CGNSSDAGTC PEGYRCLKAG ENPDHGYTSF DSFAWAFLAL FRLMTQDCWE RLYQQTLRSA GKIYMIFFML VIFL GSFYL VNLILAVVAM AYEEQNQATI AETEEKEKRF QEAMEMLKKE HEALTIRGVD TVSRSSARQR ALSAVSVLTS ALEEL EESH RKCPPCWNRF AQHYLIWECC PLWMSIKQKV KFVVMDPFAD LTITMCIVLN TLFMALEHYN MTAEFEEMLQ VGNLVF TGI FTAEMTFKII ALDPYYYFQQ GWNIFDSIIV ILSLMELGLS RMGNLSVLRS FRLLRVFKLA KSWPTLNTLI KIIGNSV GA LGNLTLVLAI IVFIFAVVGM QLFGKNYSEL RHRISDSGLL PRWHMMDFFH AFLIIFRILC GEWIETMWDC MEVSGQSL C LLVFLLVMVI GNLVVLNLFL ALLLSSFSAD NLTAPDEDGE MNNLQLALAR IQRGLRFVKR TTWDFCCGIL RRRPKKPAA LATHSQLPSC ITAPRSPPPP EVEKVPPARK ETRFEEDKRP GQGTPGDSEP VCVPIAVAES DTEDQEEDEE NGKVWWRLRK TCYRIVEHS WFETFIIFMI LLSSGALAFE DIYLEERKTI KVLLEYADKM FTYVFVLEML LKWVAYGFKK YFTNAWCWLD F LIVDVSLV SLVANTLGFA EMGPIKSLRT LRALRPLRAL SRFEGMRVVV NALVGAIPSI MNVLLVCLIF WLIFSIMGVN LF AGKFGRC INQTEGDLPL NYTIVNNKSE CESFNVTGEL YWTKVKVNFD NVGAGYLALL QVATFKGWMD IMYAAVDSRG YEE QPQWED NLYMYIYFVV FIIFGSFFTL NLFIGVIIDN FNQQKKKLGG QDIFMTEEQK KYYNAMKKLG SKKPQKPIPR PLNK YQGFI FDIVTKQAFD VTIMFLICLN MVTMMVETDD QSPEKVNILA KINLLFVAIF TGECIVKMAA LRHYYFTNSW NIFDF VVVI LSIVGTVLSD IIQKYFFSPT LFRVIRLARI GRILRLIRGA KGIRTLLFAL MMSLPALFNI GLLLFLVMFI YSIFGM ANF AYVKWEAGID DMFNFQTFAN SMLCLFQITT SAGWDGLLSP ILNTGPPYCD PNLPNSNGSR GNCGSPAVGI LFFTTYI II SFLIVVNMYI AIILENFSVA TEESTEPLSE DDFDMFYEIW EKFDPEATQF IEYLALSDFA DALSEPLRIA KPNQISLI N MDLPMVSGDR IHCMDILFAF TKRVLGESGE MDALKIQMEE KFMAANPSKI SYEPITTTLE VLFQGPGSMV SKGEELFTG VVPILVELDG DVNGHKFSVS GEGEGDATYG KLTLKFICTT GKLPVPWPTL VTTLTYGVQC FSRYPDHMKQ HDFFKSAMPE GYVQERTIF FKDDGNYKTR AEVKFEGDTL VNRIELKGID FKEDGNILGH KLEYNYNSHN VYIMADKQKN GIKVNFKIRH N IEDGSVQL ADHYQQNTPI GDGPVLLPDN HYLSTQSALS KDPNEKRDHM VLLEFVTAAG ITLGMDELYK GSDYKDDDDK |
-分子 #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 4 / コピー数: 2 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-分子 #5: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]sp...
分子 | 名称: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en タイプ: ligand / ID: 5 / コピー数: 5 / 式: 9Z9 |
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分子量 | 理論値: 544.805 Da |
Chemical component information | ChemComp-9Z9: |
-分子 #6: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyl...
分子 | 名称: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate タイプ: ligand / ID: 6 / コピー数: 11 / 式: 6OU |
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分子量 | 理論値: 717.996 Da |
Chemical component information | ChemComp-6OU: |
-分子 #7: Flecainide
分子 | 名称: Flecainide / タイプ: ligand / ID: 7 / コピー数: 1 / 式: K4D |
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分子量 | 理論値: 414.343 Da |
Chemical component information | ChemComp-K4D: |
-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
濃度 | 5.0 mg/mL | |||||||||
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緩衝液 | pH: 6 構成要素:
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グリッド | モデル: UltrAuFoil / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 雰囲気: AIR / 前処理 - 気圧: 0.133 kPa | |||||||||
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: waiting for 20s, blot for 2.5-3.5s before plunging. | |||||||||
詳細 | This sample include channel protein solubilized with GDN detergent. |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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温度 | 最低: 90.0 K / 最高: 103.0 K |
特殊光学系 | 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 |
詳細 | Squares on grids were manually screened before data collection |
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: 3838 pixel / デジタル化 - サイズ - 縦: 3710 pixel / デジタル化 - 画像ごとのフレーム数: 1-40 / 撮影したグリッド数: 2 / 実像数: 5000 / 平均露光時間: 8.0 sec. / 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 50.0 µm / 最大 デフォーカス(補正後): 3.0 µm / 最小 デフォーカス(補正後): 0.8 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): 2.8 µm / 最小 デフォーカス(公称値): 1.0 µm / 倍率(公称値): 130000 |
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 |