ion channel / calmodulin / HEAT repeat protein / MEMBRANE PROTEIN
機能・相同性
機能・相同性情報
monoatomic cation homeostasis / positive regulation of synaptic transmission, cholinergic / leak channel activity / regulation of resting membrane potential / cation channel complex / CaM pathway / Cam-PDE 1 activation / voltage-gated sodium channel activity / Sodium/Calcium exchangers / Calmodulin induced events ...monoatomic cation homeostasis / positive regulation of synaptic transmission, cholinergic / leak channel activity / regulation of resting membrane potential / cation channel complex / CaM pathway / Cam-PDE 1 activation / voltage-gated sodium channel activity / Sodium/Calcium exchangers / Calmodulin induced events / Reduction of cytosolic Ca++ levels / Activation of Ca-permeable Kainate Receptor / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / negative regulation of high voltage-gated calcium channel activity / PKA activation / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / CLEC7A (Dectin-1) induces NFAT activation / Activation of RAC1 downstream of NMDARs / negative regulation of ryanodine-sensitive calcium-release channel activity / organelle localization by membrane tethering / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / sodium channel activity / negative regulation of calcium ion export across plasma membrane / regulation of ryanodine-sensitive calcium-release channel activity / regulation of cardiac muscle cell action potential / presynaptic endocytosis / Synthesis of IP3 and IP4 in the cytosol / Phase 0 - rapid depolarisation / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / RHO GTPases activate PAKs / calcineurin-mediated signaling / monoatomic ion channel complex / regulation of cell communication by electrical coupling involved in cardiac conduction / Ion transport by P-type ATPases / calcium ion import across plasma membrane / Uptake and function of anthrax toxins / protein phosphatase activator activity / Long-term potentiation / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / DARPP-32 events / Smooth Muscle Contraction / detection of calcium ion / regulation of cardiac muscle contraction / catalytic complex / RHO GTPases activate IQGAPs / monoatomic cation channel activity / calcium channel inhibitor activity / presynaptic cytosol / cellular response to interferon-beta / Activation of AMPK downstream of NMDARs / Ion homeostasis / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / eNOS activation / Protein methylation / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / titin binding / regulation of calcium-mediated signaling / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / voltage-gated potassium channel complex / FCERI mediated Ca+2 mobilization / potassium ion transmembrane transport / calcium channel complex / substantia nigra development / FCGR3A-mediated IL10 synthesis / regulation of heart rate / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Ras activation upon Ca2+ influx through NMDA receptor / calyx of Held / bioluminescence / adenylate cyclase activator activity / positive regulation of synaptic transmission, GABAergic / VEGFR2 mediated cell proliferation / sodium ion transmembrane transport / regulation of cytokinesis / VEGFR2 mediated vascular permeability / protein serine/threonine kinase activator activity / spindle microtubule / sarcomere / positive regulation of receptor signaling pathway via JAK-STAT / Translocation of SLC2A4 (GLUT4) to the plasma membrane / generation of precursor metabolites and energy / calcium channel regulator activity / Transcriptional activation of mitochondrial biogenesis / RAF activation / response to calcium ion / cellular response to type II interferon / G2/M transition of mitotic cell cycle / calcium ion transmembrane transport / Stimuli-sensing channels / spindle pole / Signaling by RAF1 mutants / calcium-dependent protein binding / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF 類似検索 - 分子機能
UNC79 / Cation channel complex component UNC80, N-terminal / Protein UNC80, central region / Protein UNC80, C-terminal / Protein unc-79 homolog, N-terminal region / UNC80 N-terminal / Protein UNC80 central region / Protein UNC80 C-terminal region / Sodium leak channel NALCN / : ...UNC79 / Cation channel complex component UNC80, N-terminal / Protein UNC80, central region / Protein UNC80, C-terminal / Protein unc-79 homolog, N-terminal region / UNC80 N-terminal / Protein UNC80 central region / Protein UNC80 C-terminal region / Sodium leak channel NALCN / : / Voltage-dependent channel domain superfamily / : / Green fluorescent protein, GFP / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / 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 / Armadillo-type fold 類似検索 - ドメイン・相同性
Enhanced green fluorescent protein / NALCN channel auxiliary factor 1 / Calmodulin-1 / Sodium leak channel NALCN / Protein unc-80 homolog / Protein unc-79 homolog 類似検索 - 構成要素
ジャーナル: Nature / 年: 2022 タイトル: Structural architecture of the human NALCN channelosome. 著者: Marc Kschonsak / Han Chow Chua / Claudia Weidling / Nourdine Chakouri / Cameron L Noland / Katharina Schott / Timothy Chang / Christine Tam / Nidhi Patel / Christopher P Arthur / Alexander ...著者: Marc Kschonsak / Han Chow Chua / Claudia Weidling / Nourdine Chakouri / Cameron L Noland / Katharina Schott / Timothy Chang / Christine Tam / Nidhi Patel / Christopher P Arthur / Alexander Leitner / Manu Ben-Johny / Claudio Ciferri / Stephan Alexander Pless / Jian Payandeh / 要旨: Depolarizing sodium (Na) leak currents carried by the NALCN channel regulate the resting membrane potential of many neurons to modulate respiration, circadian rhythm, locomotion and pain sensitivity. ...Depolarizing sodium (Na) leak currents carried by the NALCN channel regulate the resting membrane potential of many neurons to modulate respiration, circadian rhythm, locomotion and pain sensitivity. NALCN requires FAM155A, UNC79 and UNC80 to function, but the role of these auxiliary subunits is not understood. NALCN, UNC79 and UNC80 are essential in rodents, and mutations in human NALCN and UNC80 cause severe developmental and neurological disease. Here we determined the structure of the NALCN channelosome, an approximately 1-MDa complex, as fundamental aspects about the composition, assembly and gating of this channelosome remain obscure. UNC79 and UNC80 are massive HEAT-repeat proteins that form an intertwined anti-parallel superhelical assembly, which docks intracellularly onto the NALCN-FAM155A pore-forming subcomplex. Calmodulin copurifies bound to the carboxy-terminal domain of NALCN, identifying this region as a putative modulatory hub. Single-channel analyses uncovered a low open probability for the wild-type complex, highlighting the tightly closed S6 gate in the structure, and providing a basis to interpret the altered gating properties of disease-causing variants. Key constraints between the UNC79-UNC80 subcomplex and the NALCN DI-DII and DII-DIII linkers were identified, leading to a model of channelosome gating. Our results provide a structural blueprint to understand the physiology of the NALCN channelosome and a template for drug discovery to modulate the resting membrane potential.
超分子 #1: Pentameric complex of the leak channel NALCN with FAM155A, Calmod...
超分子
名称: Pentameric complex of the leak channel NALCN with FAM155A, Calmodulin, UNC79 and UNC80 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 詳細: Calmodulin was not overexpressed but co-purified from Expi293 cells
由来(天然)
生物種: Homo sapiens (ヒト)
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分子 #1: Sodium leak channel non-selective protein,Enhanced green fluoresc...
分子
名称: Sodium leak channel non-selective protein,Enhanced green fluorescent protein タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO
凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: LEICA EM GP / 詳細: 3.5 sec blotting.
詳細
NALCN was reconstituted into lipid nanodiscs and mildly crosslinkned with 0.05% EM grade glutaraldehyde for 10 min at room temperature. Cross-linking was quenched with 9 mM Tris pH 7.5