+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7xnn | |||||||||||||||||||||
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タイトル | human KCNQ1-CaM-ML277-PIP2 complex in state B | |||||||||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / potassium voltage-gated channel / ML277 / PIP2 | |||||||||||||||||||||
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 | 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: 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
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7xnn.cif.gz | 606.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7xnn.ent.gz | 489.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7xnn.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 | 7xnn_validation.pdf.gz | 1.6 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7xnn_full_validation.pdf.gz | 1.7 MB | 表示 | |
XML形式データ | 7xnn_validation.xml.gz | 66.7 KB | 表示 | |
CIF形式データ | 7xnn_validation.cif.gz | 93.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/xn/7xnn ftp://data.pdbj.org/pub/pdb/validation_reports/xn/7xnn | 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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-要素
#1: タンパク質 | 分子量: 19615.445 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CALM3, CALML2, CAM3, CAMC, CAMIII / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DP25 #2: タンパク質 | 分子量: 76487.297 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: KCNQ1, KCNA8, KCNA9, KVLQT1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P51787 #3: 化合物 | ChemComp-K / #4: 化合物 | ChemComp-I0S / ( #5: 化合物 | ChemComp-PIO / [( 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: human KCNQ1-CaM-ML277-PIP2 complex in state B / タイプ: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1-#2 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 8 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
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 / 最大 デフォーカス(公称値): -1300 nm / 最小 デフォーカス(公称値): -1100 nm |
撮影 | 電子線照射量: 64 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 2.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 257550 / 対称性のタイプ: POINT |