登録情報 データベース : EMDB / ID : EMD-7539 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of the human SK4/calmodulin channel complex in the Ca2+ bound state II マップデータhuman SK4/calmodulin channel complex in the Ca2+ bound state II: sharpened, filtered map 詳細 試料複合体 : human SK4/calmodulin channel complexタンパク質・ペプチド : Intermediate conductance calcium-activated potassium channel protein 4タンパク質・ペプチド : Calmodulin-1リガンド : CALCIUM ION 詳細 キーワード ion channel / neuroscience / calmodulin / 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
intermediate conductance calcium-activated potassium channel activity / small conductance calcium-activated potassium channel activity / saliva secretion / Ca2+ activated K+ channels / calcium-activated potassium channel activity / stabilization of membrane potential / positive regulation of potassium ion transmembrane transport / cell volume homeostasis / CaM pathway / Cam-PDE 1 activation ... intermediate conductance calcium-activated potassium channel activity / small conductance calcium-activated potassium channel activity / saliva secretion / Ca2+ activated K+ channels / calcium-activated potassium channel activity / stabilization of membrane potential / positive regulation of potassium ion transmembrane transport / cell volume homeostasis / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / phospholipid translocation / Calmodulin induced events / Reduction of cytosolic Ca++ levels / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Activation of Ca-permeable Kainate Receptor / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / positive regulation of cyclic-nucleotide phosphodiesterase activity / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / regulation of cardiac muscle cell action potential / Activation of RAC1 downstream of NMDARs / immune system process / positive regulation of T cell receptor signaling pathway / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / Negative regulation of NMDA receptor-mediated neuronal transmission / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / Unblocking of NMDA receptors, glutamate binding and activation / Phase 0 - rapid depolarisation / protein phosphatase activator activity / potassium channel activity / RHO GTPases activate PAKs / positive regulation of phosphoprotein phosphatase activity / Ion transport by P-type ATPases / Long-term potentiation / Uptake and function of anthrax toxins / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / catalytic complex / DARPP-32 events / detection of calcium ion / regulation of cardiac muscle contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / calcium channel inhibitor activity / cellular response to interferon-beta / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Protein methylation / eNOS activation / Activation of AMPK downstream of NMDARs / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / positive regulation of protein dephosphorylation / Ion homeostasis / regulation of calcium-mediated signaling / regulation of ryanodine-sensitive calcium-release channel activity / titin binding / positive regulation of protein autophosphorylation / voltage-gated potassium channel complex / potassium ion transmembrane transport / sperm midpiece / calcium channel complex / substantia nigra development / adenylate cyclase activator activity / Ras activation upon Ca2+ influx through NMDA receptor / regulation of heart rate / sarcomere / protein serine/threonine kinase activator activity / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / VEGFR2 mediated vascular permeability / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / positive regulation of peptidyl-threonine phosphorylation / VEGFR2 mediated cell proliferation / regulation of cytokinesis / establishment of localization in cell / Translocation of SLC2A4 (GLUT4) to the plasma membrane / positive regulation of protein secretion / spindle microtubule / RAF activation / positive regulation of receptor signaling pathway via JAK-STAT / potassium ion transport / Transcriptional activation of mitochondrial biogenesis / positive regulation of protein serine/threonine kinase activity / Stimuli-sensing channels / defense response / cellular response to type II interferon / spindle pole / response to calcium ion 類似検索 - 分子機能 Calmodulin-binding domain / Potassium channel, calcium-activated, SK / SK, calmodulin-binding domain superfamily / Calmodulin binding domain / Calcium-activated SK potassium channel / Calmodulin binding domain / : / Potassium channel domain / Ion channel / EF-hand domain pair ... Calmodulin-binding domain / Potassium channel, calcium-activated, SK / SK, calmodulin-binding domain superfamily / Calmodulin binding domain / Calcium-activated SK potassium channel / Calmodulin binding domain / : / Potassium channel domain / Ion 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 / EF-hand domain pair 類似検索 - ドメイン・相同性 Intermediate conductance calcium-activated potassium channel protein 4 / Calmodulin-1 類似検索 - 構成要素生物種 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 : 4.7 Å 詳細 データ登録者Lee CH / MacKinnon R 資金援助 米国, 2件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI) GM43949 米国 Howard Hughes Medical Institute (HHMI) 米国
引用ジャーナル : Science / 年 : 2018タイトル : Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures.著者 : Chia-Hsueh Lee / Roderick MacKinnon / 要旨 : Small-conductance Ca-activated K (SK) channels mediate neuron excitability and are associated with synaptic transmission and plasticity. They also regulate immune responses and the size of blood ... Small-conductance Ca-activated K (SK) channels mediate neuron excitability and are associated with synaptic transmission and plasticity. They also regulate immune responses and the size of blood cells. Activation of SK channels requires calmodulin (CaM), but how CaM binds and opens SK channels has been unclear. Here we report cryo-electron microscopy (cryo-EM) structures of a human SK4-CaM channel complex in closed and activated states at 3.4- and 3.5-angstrom resolution, respectively. Four CaM molecules bind to one channel tetramer. Each lobe of CaM serves a distinct function: The C-lobe binds to the channel constitutively, whereas the N-lobe interacts with the S4-S5 linker in a Ca-dependent manner. The S4-S5 linker, which contains two distinct helices, undergoes conformational changes upon CaM binding to open the channel pore. These structures reveal the gating mechanism of SK channels and provide a basis for understanding SK channel pharmacology. 履歴 登録 2018年3月8日 - ヘッダ(付随情報) 公開 2018年5月2日 - マップ公開 2018年5月2日 - 更新 2024年3月13日 - 現状 2024年3月13日 処理サイト : RCSB / 状態 : 公開
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