登録情報 データベース : PDB / ID : 7cr4 構造の表示 ダウンロードとリンクタイトル human KCNQ2-CaM in complex with ztz240 要素Calmodulin-3 Potassium voltage-gated channel subfamily KQT member 2 詳細キーワード TRANSPORT PROTEIN / ion channel機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
axon initial segment / Voltage gated Potassium channels / node of Ranvier / Interaction between L1 and Ankyrins / ankyrin binding / 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 / regulation of cardiac muscle cell action potential / positive regulation of ryanodine-sensitive calcium-release channel activity ... axon initial segment / Voltage gated Potassium channels / node of Ranvier / Interaction between L1 and Ankyrins / ankyrin binding / 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 / 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 / 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 / positive regulation of protein autophosphorylation / potassium ion transmembrane transport / 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 / regulation of cytokinesis / positive regulation of peptidyl-threonine phosphorylation / 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 / nervous system development / chemical synaptic transmission / vesicle / transmembrane transporter binding / calmodulin binding / G protein-coupled receptor signaling pathway / centrosome / synapse / calcium ion binding / protein kinase binding / protein-containing complex / nucleus / plasma membrane / cytoplasm 類似検索 - 分子機能 Potassium channel, voltage dependent, KCNQ2 / Ankyrin-G binding site / Ankyrin-G binding motif of KCNQ2-3 / Unstructured region on Potassium channel subunit alpha KvLQT2 / Potassium channel, voltage dependent, KCNQ / Potassium channel, voltage dependent, KCNQ, C-terminal / KCNQ voltage-gated potassium channel / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site ... Potassium channel, voltage dependent, KCNQ2 / Ankyrin-G binding site / Ankyrin-G binding motif of KCNQ2-3 / Unstructured region on Potassium channel subunit alpha KvLQT2 / Potassium channel, voltage dependent, KCNQ / Potassium channel, voltage dependent, KCNQ, C-terminal / KCNQ voltage-gated potassium channel / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / Ion transport domain / Ion transport protein / EF-hand domain pair 類似検索 - ドメイン・相同性 N-(6-chloranylpyridin-3-yl)-4-fluoranyl-benzamide / Potassium voltage-gated channel subfamily KQT member 2 / Calmodulin-3 類似検索 - 構成要素生物種 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 : 3.9 Å 詳細データ登録者 Li, X. / Lv, D. / Wang, J. / Ye, S. / Guo, J. 資金援助 中国, 2件 詳細 詳細を隠す組織 認可番号 国 Ministry of Science and Technology (MoST, China) 2018YFA0508100 中国 National Natural Science Foundation of China (NSFC) 31870724 中国
引用ジャーナル : Cell Res / 年 : 2021タイトル : Molecular basis for ligand activation of the human KCNQ2 channel.著者 : Xiaoxiao Li / Qiansen Zhang / Peipei Guo / Jie Fu / Lianghe Mei / Dashuai Lv / Jiangqin Wang / Dongwu Lai / Sheng Ye / Huaiyu Yang / Jiangtao Guo / 要旨 : The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy, pain and several other diseases related to neuronal hyper- ... The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy, pain and several other diseases related to neuronal hyper-excitability. A list of synthetic compounds have been developed to directly activate KCNQ2, yet our knowledge of their activation mechanism is limited, due to lack of high-resolution structures. Here, we report cryo-electron microscopy (cryo-EM) structures of the human KCNQ2 determined in apo state and in complex with two activators, ztz240 or retigabine, which activate KCNQ2 through different mechanisms. The activator-bound structures, along with electrophysiology analysis, reveal that ztz240 binds at the voltage-sensing domain and directly stabilizes it at the activated state, whereas retigabine binds at the pore domain and activates the channel by an allosteric modulation. By accurately defining ligand-binding sites, these KCNQ2 structures not only reveal different ligand recognition and activation mechanisms, but also provide a structural basis for drug optimization and design. 履歴 登録 2020年8月12日 登録サイト : PDBJ / 処理サイト : PDBJ改定 1.0 2020年9月16日 Provider : repository / タイプ : Initial release改定 1.1 2020年11月11日 Group : Structure summary / カテゴリ : chem_comp / Item : _chem_comp.pdbx_synonyms改定 1.2 2021年1月13日 Group : Database references / カテゴリ : citationItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year 改定 1.3 2024年3月27日 Group : Data collection / Database references / カテゴリ : chem_comp_atom / chem_comp_bond / database_2Item : _database_2.pdbx_DOI / _database_2.pdbx_database_accession
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