登録情報 データベース : EMDB / ID : EMD-37474 ダウンロードとリンクタイトル Human L-type voltage-gated calcium channel Cav1.2 in the presence of calciseptine, amlodipine and pinaverium at 2.9 Angstrom resolution マップデータ 詳細 試料複合体 : Cav1.2タンパク質・ペプチド : Voltage-dependent L-type calcium channel subunit alpha-1Cタンパク質・ペプチド : Voltage-dependent calcium channel subunit alpha-2/delta-1タンパク質・ペプチド : Voltage-dependent L-type calcium channel subunit beta-3タンパク質・ペプチド : Calciseptinリガンド : CALCIUM IONリガンド : CHOLESTEROLリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoateリガンド : 1,2-Distearoyl-sn-glycerophosphoethanolamineリガンド : amlodipine 残り3件を表示 表示を減らす 詳細 キーワード Cav1.2 / Channels / Calcium Ion-Selective / TRANSPORT PROTEIN / MEMBRANE PROTEIN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
: / voltage-gated calcium channel activity involved in AV node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / immune system development / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / membrane depolarization during atrial cardiac muscle cell action potential / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel ... : / voltage-gated calcium channel activity involved in AV node cell action potential / voltage-gated calcium channel activity involved in cardiac muscle cell action potential / immune system development / regulation of membrane repolarization during action potential / Presynaptic depolarization and calcium channel opening / positive regulation of high voltage-gated calcium channel activity / membrane depolarization during atrial cardiac muscle cell action potential / Phase 2 - plateau phase / calcium ion transmembrane transport via high voltage-gated calcium channel / membrane depolarization during AV node cell action potential / membrane depolarization during bundle of His cell action potential / positive regulation of adenylate cyclase activity / high voltage-gated calcium channel activity / cardiac conduction / L-type voltage-gated calcium channel complex / membrane depolarization during cardiac muscle cell action potential / regulation of ventricular cardiac muscle cell action potential / cardiac muscle cell action potential involved in contraction / camera-type eye development / regulation of ventricular cardiac muscle cell membrane repolarization / NCAM1 interactions / embryonic forelimb morphogenesis / calcium ion transport into cytosol / cell communication by electrical coupling involved in cardiac conduction / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / voltage-gated calcium channel complex / neuromuscular junction development / Phase 0 - rapid depolarisation / neuronal dense core vesicle / alpha-actinin binding / regulation of heart rate by cardiac conduction / regulation of calcium ion transport / calcium channel regulator activity / calcium ion import across plasma membrane / voltage-gated calcium channel activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / sarcoplasmic reticulum / Regulation of insulin secretion / protein localization to plasma membrane / calcium ion transmembrane transport / postsynaptic density membrane / Z disc / Adrenaline,noradrenaline inhibits insulin secretion / cellular response to amyloid-beta / calcium ion transport / heart development / T cell receptor signaling pathway / toxin activity / positive regulation of cytosolic calcium ion concentration / chemical synaptic transmission / perikaryon / postsynaptic density / calmodulin binding / synapse / dendrite / extracellular exosome / extracellular region / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 Voltage-dependent calcium channel, L-type, beta-3 subunit / Voltage-dependent L-type calcium channel subunit beta-3, SH3 domain / Voltage-dependent calcium channel, L-type, alpha-1C subunit / Voltage-dependent L-type calcium channel subunit beta-1-4, N-terminal A domain / Voltage-dependent calcium channel, L-type, beta subunit / Voltage gated calcium channel subunit beta domain 4Aa N terminal / Voltage-gated calcium channel subunit alpha, C-terminal / Voltage-gated calcium channel subunit alpha, C-term / Voltage-dependent calcium channel, L-type, alpha-1 subunit / VWA N-terminal ... Voltage-dependent calcium channel, L-type, beta-3 subunit / Voltage-dependent L-type calcium channel subunit beta-3, SH3 domain / Voltage-dependent calcium channel, L-type, alpha-1C subunit / Voltage-dependent L-type calcium channel subunit beta-1-4, N-terminal A domain / Voltage-dependent calcium channel, L-type, beta subunit / Voltage gated calcium channel subunit beta domain 4Aa N terminal / Voltage-gated calcium channel subunit alpha, C-terminal / Voltage-gated calcium channel subunit alpha, C-term / Voltage-dependent calcium channel, L-type, alpha-1 subunit / VWA N-terminal / Voltage-dependent calcium channel, alpha-2/delta subunit, conserved region / VWA N-terminal / Neuronal voltage-dependent calcium channel alpha 2acd / Voltage-dependent calcium channel, alpha-1 subunit, IQ domain / Voltage gated calcium channel IQ domain / Voltage gated calcium channel IQ domain / Voltage-dependent calcium channel, alpha-1 subunit / Voltage-dependent L-type calcium channel, IQ-associated domain / Voltage-dependent L-type calcium channel, IQ-associated / Snake toxins signature. / Snake toxin, conserved site / Guanylate kinase/L-type calcium channel beta subunit / Guanylate kinase / Guanylate kinase homologues. / Snake toxin-like superfamily / von Willebrand factor type A domain / von Willebrand factor (vWF) type A domain / VWFA domain profile. / Voltage-dependent channel domain superfamily / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Ion transport domain / Ion transport protein / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Calciseptin / Voltage-dependent L-type calcium channel subunit beta-3 / Voltage-dependent calcium channel subunit alpha-2/delta-1 / Voltage-dependent L-type calcium channel subunit alpha-1C 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Dendroaspis polylepis polylepis (コブラ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.9 Å 詳細 データ登録者Gao S / Yao X / Yan N 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 Beijing Nova Program Z191100001119127 中国
引用ジャーナル : Cell / 年 : 2023タイトル : Structural basis for human Ca1.2 inhibition by multiple drugs and the neurotoxin calciseptine.著者: Shuai Gao / Xia Yao / Jiaofeng Chen / Gaoxingyu Huang / Xiao Fan / Lingfeng Xue / Zhangqiang Li / Tong Wu / Yupeng Zheng / Jian Huang / Xueqin Jin / Yan Wang / Zhifei Wang / Yong Yu / Lei Liu ... 著者 : Shuai Gao / Xia Yao / Jiaofeng Chen / Gaoxingyu Huang / Xiao Fan / Lingfeng Xue / Zhangqiang Li / Tong Wu / Yupeng Zheng / Jian Huang / Xueqin Jin / Yan Wang / Zhifei Wang / Yong Yu / Lei Liu / Xiaojing Pan / Chen Song / Nieng Yan / 要旨 : Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in complex with several drugs, as well ... Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSD. Calciseptine sits on the shoulder of the pore domain, away from the permeation path. In contrast, when pinaverium bromide, an antispasmodic drug, is inserted into a cavity reminiscent of the IFM-binding site in Na channels, a series of structural changes occur, including upward movement of VSD coupled with dilation of the selectivity filter and its surrounding segments in repeat III. Meanwhile, S4-5 merges with S5 to become a single helix, resulting in a widened but still non-conductive intracellular gate. 履歴 登録 2023年9月17日 - ヘッダ(付随情報) 公開 2023年12月6日 - マップ公開 2023年12月6日 - 更新 2023年12月6日 - 現状 2023年12月6日 処理サイト : PDBj / 状態 : 公開
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