+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-22621 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cardiac Sodium channel with toxin bound | |||||||||
マップデータ | cryo-EM map of sodium channel with toxin | |||||||||
試料 |
| |||||||||
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 atrial cardiac muscle cell membrane repolarization / regulation of ventricular cardiac muscle cell membrane depolarization / membrane depolarization during atrial cardiac muscle cell action potential / cardiac ventricle development / regulation of sodium ion transmembrane transport / voltage-gated sodium channel activity involved in Purkinje myocyte action potential / telencephalon development / 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 / 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 / sodium channel inhibitor activity / ventricular cardiac muscle cell action potential / cardiac muscle cell action potential involved in contraction / membrane depolarization during action potential / voltage-gated sodium channel complex / regulation of ventricular cardiac muscle cell membrane repolarization / regulation of cardiac muscle cell contraction / voltage-gated sodium channel activity / ankyrin binding / positive regulation of heart rate / fibroblast growth factor binding / sodium ion transport / odontogenesis of dentin-containing tooth / nitric-oxide synthase binding / regulation of heart rate by cardiac conduction / 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 / defense response / toxin 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 region / membrane / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | Rattus norvegicus (ドブネズミ) / Leiurus hebraeus (サソリ) / Aequorea victoria (オワンクラゲ) / Deathstalker scorpion (unknown) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | |||||||||
データ登録者 | Jiang D / Catterall WA | |||||||||
資金援助 | 米国, 2件
| |||||||||
引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Structural basis for voltage-sensor trapping of the cardiac sodium channel by a deathstalker scorpion toxin. 著者: Daohua Jiang / Lige Tonggu / Tamer M Gamal El-Din / Richard Banh / Régis Pomès / Ning Zheng / William A Catterall / 要旨: Voltage-gated sodium (Na) channels initiate action potentials in excitable cells, and their function is altered by potent gating-modifier toxins. The α-toxin LqhIII from the deathstalker scorpion ...Voltage-gated sodium (Na) channels initiate action potentials in excitable cells, and their function is altered by potent gating-modifier toxins. The α-toxin LqhIII from the deathstalker scorpion inhibits fast inactivation of cardiac Na1.5 channels with IC = 11.4 nM. Here we reveal the structure of LqhIII bound to Na1.5 at 3.3 Å resolution by cryo-EM. LqhIII anchors on top of voltage-sensing domain IV, wedged between the S1-S2 and S3-S4 linkers, which traps the gating charges of the S4 segment in a unique intermediate-activated state stabilized by four ion-pairs. This conformational change is propagated inward to weaken binding of the fast inactivation gate and favor opening the activation gate. However, these changes do not permit Na permeation, revealing why LqhIII slows inactivation of Na channels but does not open them. Our results provide important insights into the structural basis for gating-modifier toxin binding, voltage-sensor trapping, and fast inactivation of Na channels. | |||||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
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_22621.map.gz | 59.9 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-22621-v30.xml emd-22621.xml | 16.8 KB 16.8 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_22621_fsc.xml | 9.1 KB | 表示 | FSCデータファイル |
画像 | emd_22621.png | 141.4 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-22621 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22621 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_22621_validation.pdf.gz | 499.9 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_22621_full_validation.pdf.gz | 499.4 KB | 表示 | |
XML形式データ | emd_22621_validation.xml.gz | 10.7 KB | 表示 | |
CIF形式データ | emd_22621_validation.cif.gz | 14 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22621 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22621 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「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_22621.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | cryo-EM map of sodium channel with toxin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.056 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-試料の構成要素
-全体 : Cryo-EM map for sodium channel and scorpion toxin complex
全体 | 名称: Cryo-EM map for sodium channel and scorpion toxin complex |
---|---|
要素 |
|
-超分子 #1: Cryo-EM map for sodium channel and scorpion toxin complex
超分子 | 名称: Cryo-EM map for sodium channel and scorpion toxin complex タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
---|---|
分子量 | 理論値: 250 KDa |
-超分子 #2: Sodium channel protein type 5 subunit alpha
超分子 | 名称: Sodium channel protein type 5 subunit alpha / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1 |
---|---|
由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
組換発現 | 生物種: Homo sapiens (ヒト) |
-超分子 #3: Alpha-like toxin Lqh3
超分子 | 名称: Alpha-like toxin Lqh3 / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #2 |
---|---|
由来(天然) | 生物種: Leiurus hebraeus (サソリ) |
-分子 #1: Sodium channel protein type 5 subunit alpha, Enhanced Green fluor...
分子 | 名称: Sodium channel protein type 5 subunit alpha, Enhanced Green fluorescent protein タイプ: protein_or_peptide / ID: 1 詳細: Loops truncated sodium channel with EGFP and FLAG tag fused at the C-terminus コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Aequorea victoria (オワンクラゲ) |
分子量 | 理論値: 209.037781 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
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 #2: Alpha-like toxin Lqh3
分子 | 名称: Alpha-like toxin Lqh3 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Deathstalker scorpion (unknown) |
分子量 | 理論値: 7.065984 KDa |
配列 | 文字列: VRDGYIAQPE NCVYHCFPGS SGCDTLCKEK GGTSGHCGFK VGHGLACWCN ALPDNVGIIV EGEKCHS |
-分子 #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 5 / コピー数: 1 / 式: NAG |
---|---|
分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-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 |
---|---|
分子量 | 理論値: 717.996 Da |
Chemical component information | ChemComp-6OU: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 4.5 mg/mL | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
緩衝液 | pH: 6 構成要素:
| ||||||||||||
グリッド | モデル: UltrAuFoil / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE | ||||||||||||
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 |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
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: 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: 100.0 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): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
+画像解析
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: RIGID BODY FIT / 温度因子: 59 |
---|---|
得られたモデル | PDB-7k18: |