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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 7byl | ||||||
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タイトル | Cryo-EM structure of human KCNQ4 | ||||||
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![]() | MEMBRANE PROTEIN / KCNQ / Channel / Calmodulin / PIP2 | ||||||
機能・相同性 | ![]() Voltage gated Potassium channels / Sensory processing of sound by outer hair cells of the cochlea / Sensory processing of sound by inner hair cells of the cochlea / negative regulation of high voltage-gated calcium channel activity / positive regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of calcium ion export across plasma membrane / inner ear morphogenesis / regulation of cardiac muscle cell action potential / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction ...Voltage gated Potassium channels / Sensory processing of sound by outer hair cells of the cochlea / Sensory processing of sound by inner hair cells of the cochlea / negative regulation of high voltage-gated calcium channel activity / positive regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of calcium ion export across plasma membrane / inner ear morphogenesis / regulation of cardiac muscle cell action potential / 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 / voltage-gated potassium channel activity / potassium channel activity / protein phosphatase activator activity / positive regulation of phosphoprotein phosphatase activity / adenylate cyclase binding / catalytic complex / detection of calcium ion / regulation of cardiac muscle contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / positive regulation of protein dephosphorylation / regulation of calcium-mediated signaling / titin binding / potassium ion transmembrane transport / positive regulation of protein autophosphorylation / voltage-gated potassium channel complex / sperm midpiece / calcium channel complex / substantia nigra development / adenylate cyclase activator activity / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / bioluminescence / basal plasma membrane / positive regulation of peptidyl-threonine phosphorylation / regulation of cytokinesis / generation of precursor metabolites and energy / sensory perception of sound / potassium ion transport / positive regulation of protein serine/threonine kinase activity / spindle microtubule / spindle pole / response to calcium ion / G2/M transition of mitotic cell cycle / calcium-dependent protein binding / myelin sheath / vesicle / transmembrane transporter binding / G protein-coupled receptor signaling pathway / centrosome / calcium ion binding / protein kinase binding / protein-containing complex / nucleus / plasma membrane / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() ![]() | ||||||
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 | ||||||
![]() | Shen, H. / Li, T. / Yue, Z. | ||||||
![]() | ![]() タイトル: Structural Basis for the Modulation of Human KCNQ4 by Small-Molecule Drugs. 著者: Tian Li / Kun Wu / Zhenlei Yue / Yifei Wang / Fan Zhang / Huaizong Shen / ![]() 要旨: Among the five KCNQ channels, also known as the K7 voltage-gated potassium (K) channels, KCNQ2-KCNQ5 control neuronal excitability. Dysfunctions of KCNQ2-KCNQ5 are associated with neurological ...Among the five KCNQ channels, also known as the K7 voltage-gated potassium (K) channels, KCNQ2-KCNQ5 control neuronal excitability. Dysfunctions of KCNQ2-KCNQ5 are associated with neurological disorders such as epilepsy, deafness, and neuropathic pain. Here, we report the cryoelectron microscopy (cryo-EM) structures of human KCNQ4 and its complexes with the opener retigabine or the blocker linopirdine at overall resolutions of 2.5, 3.1, and 3.3 Å, respectively. In all structures, a phosphatidylinositol 4,5-bisphosphate (PIP) molecule inserts its head group into a cavity within each voltage-sensing domain (VSD), revealing an unobserved binding mode for PIP. Retigabine nestles in each fenestration, inducing local shifts. Instead of staying within the central pore, linopirdine resides in a cytosolic cavity underneath the inner gate. Electrophysiological analyses of various mutants corroborated the structural observations. Our studies reveal the molecular basis for the modulatory mechanism of neuronal KCNQ channels and provide a framework for structure-facilitated drug discovery targeting these important channels. | ||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 428.9 KB | 表示 | ![]() |
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PDB形式 | ![]() | 321.5 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 1.1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.2 MB | 表示 | |
XML形式データ | ![]() | 61.9 KB | 表示 | |
CIF形式データ | ![]() | 83.6 KB | 表示 | |
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-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 109327.836 Da / 分子数: 4 / 変異: F64L/S65T/K107T/A206K / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() ![]() 遺伝子: GFP, KCNQ4 / 発現宿主: ![]() #2: タンパク質 | 分子量: 16852.545 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #3: 化合物 | ChemComp-PT5 / [( #4: 化合物 | ChemComp-K / #5: 水 | ChemComp-HOH / | 研究の焦点であるリガンドがあるか | Y | |
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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 |
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試料調製
構成要素 | 名称: Complex of human KCNQ4 and Calmodulin / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
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 |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.17.1_3660: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
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: 192507 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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