+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-33319 | |||||||||||||||||||||
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タイトル | human KCNQ1-CaM-ML277-PIP2 complex in state B | |||||||||||||||||||||
マップデータ | ||||||||||||||||||||||
試料 |
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キーワード | potassium voltage-gated channel / ML277 / PIP2 / MEMBRANE PROTEIN | |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 gastrin-induced gastric acid secretion / corticosterone secretion / voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization / basolateral part of cell / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / lumenal side of membrane / rhythmic behavior / negative regulation of voltage-gated potassium channel activity / regulation of gastric acid secretion / stomach development ...gastrin-induced gastric acid secretion / corticosterone secretion / voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization / basolateral part of cell / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / lumenal side of membrane / rhythmic behavior / negative regulation of voltage-gated potassium channel activity / regulation of gastric acid secretion / stomach development / membrane repolarization during atrial cardiac muscle cell action potential / iodide transport / Phase 3 - rapid repolarisation / detection of mechanical stimulus involved in sensory perception of sound / membrane repolarization during action potential / regulation of atrial cardiac muscle cell membrane repolarization / Phase 2 - plateau phase / intracellular chloride ion homeostasis / membrane repolarization during ventricular cardiac muscle cell action potential / membrane repolarization during cardiac muscle cell action potential / negative regulation of delayed rectifier potassium channel activity / renal sodium ion absorption / potassium ion export across plasma membrane / atrial cardiac muscle cell action potential / auditory receptor cell development / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / regulation of membrane repolarization / protein phosphatase 1 binding / positive regulation of potassium ion transmembrane transport / delayed rectifier potassium channel activity / Voltage gated Potassium channels / potassium ion homeostasis / outward rectifier potassium channel activity / ventricular cardiac muscle cell action potential / non-motile cilium assembly / regulation of ventricular cardiac muscle cell membrane repolarization / cardiac muscle cell contraction / intestinal absorption / inner ear morphogenesis / negative regulation of high voltage-gated calcium channel activity / monoatomic ion channel complex / ciliary base / positive regulation of cyclic-nucleotide phosphodiesterase activity / positive regulation of heart rate / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / regulation of heart contraction / adrenergic receptor signaling pathway / action potential / cochlea development / renal absorption / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-threonine phosphorylation / protein kinase A regulatory subunit binding / negative regulation of ryanodine-sensitive calcium-release channel activity / adenylate cyclase activator activity / protein phosphatase activator activity / potassium ion import across plasma membrane / regulation of heart rate by cardiac conduction / protein kinase A catalytic subunit binding / : / inner ear development / social behavior / adenylate cyclase binding / voltage-gated potassium channel activity / catalytic complex / regulation of cardiac muscle contraction / detection of calcium ion / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / voltage-gated potassium channel complex / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / cardiac muscle contraction / : / phosphatidylinositol-4,5-bisphosphate binding / titin binding / positive regulation of protein autophosphorylation / regulation of calcium-mediated signaling / cellular response to cAMP / sperm midpiece / potassium ion transmembrane transport / transport vesicle / calcium channel complex / positive regulation of cardiac muscle contraction / cellular response to epinephrine stimulus / substantia nigra development / sarcomere / regulation of heart rate / protein serine/threonine kinase activator activity / erythrocyte differentiation / regulation of cytokinesis / positive regulation of peptidyl-threonine phosphorylation / spindle microtubule / sensory perception of sound / response to insulin / cytoplasmic vesicle membrane / positive regulation of protein serine/threonine kinase activity / regulation of blood pressure / spindle pole / response to calcium ion 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | Homo sapiens (ヒト) | |||||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.5 Å | |||||||||||||||||||||
データ登録者 | Ma D / Guo J | |||||||||||||||||||||
資金援助 | 中国, 6件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2022 タイトル: Structural mechanisms for the activation of human cardiac KCNQ1 channel by electro-mechanical coupling enhancers. 著者: Demin Ma / Ling Zhong / Zhenzhen Yan / Jing Yao / Yan Zhang / Fan Ye / Yuan Huang / Dongwu Lai / Wei Yang / Panpan Hou / Jiangtao Guo / 要旨: The cardiac KCNQ1 potassium channel carries the important current and controls the heart rhythm. Hundreds of mutations in KCNQ1 can cause life-threatening cardiac arrhythmia. Although KCNQ1 ...The cardiac KCNQ1 potassium channel carries the important current and controls the heart rhythm. Hundreds of mutations in KCNQ1 can cause life-threatening cardiac arrhythmia. Although KCNQ1 structures have been recently resolved, the structural basis for the dynamic electro-mechanical coupling, also known as the voltage sensor domain-pore domain (VSD-PD) coupling, remains largely unknown. In this study, utilizing two VSD-PD coupling enhancers, namely, the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP) and a small-molecule ML277, we determined 2.5-3.5 Å resolution cryo-electron microscopy structures of full-length human KCNQ1-calmodulin (CaM) complex in the apo closed, ML277-bound open, and ML277-PIP-bound open states. ML277 binds at the "elbow" pocket above the S4-S5 linker and directly induces an upward movement of the S4-S5 linker and the opening of the activation gate without affecting the C-terminal domain (CTD) of KCNQ1. PIP binds at the cleft between the VSD and the PD and brings a large structural rearrangement of the CTD together with the CaM to activate the PD. These findings not only elucidate the structural basis for the dynamic VSD-PD coupling process during KCNQ1 gating but also pave the way to develop new therapeutics for anti-arrhythmia. | |||||||||||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_33319.map.gz | 41.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-33319-v30.xml emd-33319.xml | 17.5 KB 17.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_33319.png | 67.3 KB | ||
Filedesc metadata | emd-33319.cif.gz | 6.1 KB | ||
その他 | emd_33319_half_map_1.map.gz emd_33319_half_map_2.map.gz | 37.1 MB 37.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-33319 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33319 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_33319_validation.pdf.gz | 731.7 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_33319_full_validation.pdf.gz | 731.3 KB | 表示 | |
XML形式データ | emd_33319_validation.xml.gz | 11.5 KB | 表示 | |
CIF形式データ | emd_33319_validation.cif.gz | 13.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33319 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33319 | 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_33319.map.gz / 形式: CCP4 / 大きさ: 52.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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: 1.014 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #1
ファイル | emd_33319_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_33319_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : human KCNQ1-CaM-ML277-PIP2 complex in state B
全体 | 名称: human KCNQ1-CaM-ML277-PIP2 complex in state B |
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要素 |
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-超分子 #1: human KCNQ1-CaM-ML277-PIP2 complex in state B
超分子 | 名称: human KCNQ1-CaM-ML277-PIP2 complex in state B / タイプ: organelle_or_cellular_component / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Calmodulin-3
分子 | 名称: Calmodulin-3 / タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 19.615445 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK LEGGSSGGLV P RGSGGSSG GHHHHHHHH UniProtKB: Calmodulin-3 |
-分子 #2: Potassium voltage-gated channel subfamily KQT member 1
分子 | 名称: Potassium voltage-gated channel subfamily KQT member 1 タイプ: protein_or_peptide / ID: 2 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 76.487297 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MAAASSPPRA ERKRWGWGRL PGARRGSAGL AKKCPFSLEL AEGGPAGGAL YAPIAPGAPG PAPPASPAAP AAPPVASDLG PRPPVSLDP RVSIYSTRRP VLARTHVQGR VYNFLERPTG WKCFVYHFAV FLIVLVCLIF SVLSTIEQYA ALATGTLFWM E IVLVVFFG ...文字列: MAAASSPPRA ERKRWGWGRL PGARRGSAGL AKKCPFSLEL AEGGPAGGAL YAPIAPGAPG PAPPASPAAP AAPPVASDLG PRPPVSLDP RVSIYSTRRP VLARTHVQGR VYNFLERPTG WKCFVYHFAV FLIVLVCLIF SVLSTIEQYA ALATGTLFWM E IVLVVFFG TEYVVRLWSA GCRSKYVGLW GRLRFARKPI SIIDLIVVVA SMVVLCVGSK GQVFATSAIR GIRFLQILRM LH VDRQGGT WRLLGSVVFI HRQELITTLY IGFLGLIFSS YFVYLAEKDA VNESGRVEFG SYADALWWGV VTVTTIGYGD KVP QTWVGK TIASCFSVFA ISFFALPAGI LGSGFALKVQ QKQRQKHFNR QIPAAASLIQ TAWRCYAAEN PDSSTWKIYI RKAP RSHTL LSPSPKPKKS VVVKKKKFKL DKDNGVTPGE KMLTVPHITC DPPEERRLDH FSVDGYDSSV RKSPTLLEVS MPHFM RTNS FAEDLDLEGE TLLTPITHIS QLREHHRATI KVIRRMQYFV AKKKFQQARK PYDVRDVIEQ YSQGHLNLMV RIKELQ RRL DQSIGKPSLF ISVSEKSKDR GSNTIGARLN RVEDKVTQLD QRLALITDML HQLLSLHGGS TPGSGGPPRE GGAHITQ PC GSGGSVDPEL FLPSNTLPTY EQLTVPRRGP DEGSLEGGSS GGWSHPQFEK UniProtKB: Potassium voltage-gated channel subfamily KQT member 1 |
-分子 #3: POTASSIUM ION
分子 | 名称: POTASSIUM ION / タイプ: ligand / ID: 3 / コピー数: 4 / 式: K |
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分子量 | 理論値: 39.098 Da |
-分子 #4: (2R)-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-1-(4-methylbenzene-...
分子 | 名称: (2R)-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-1-(4-methylbenzene-1-sulfonyl)piperidine-2-carboxamide タイプ: ligand / ID: 4 / コピー数: 4 / 式: I0S |
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分子量 | 理論値: 471.592 Da |
Chemical component information | ChemComp-I0S: |
-分子 #5: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(o...
分子 | 名称: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate タイプ: ligand / ID: 5 / コピー数: 4 / 式: PIO |
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分子量 | 理論値: 746.566 Da |
Chemical component information | ChemComp-PIO: |
-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
緩衝液 | pH: 8 |
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凍結 | 凍結剤: ETHANE |
-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) 平均電子線量: 64.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): -1.3 µm / 最小 デフォーカス(公称値): -1.1 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 257550 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |