+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7wji | ||||||
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タイトル | Architecture of the human NALCN channelosome | ||||||
要素 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / ion channel (イオンチャネル) / channelosome / NALCN | ||||||
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 / viral tegument / cation channel complex / sodium channel activity / voltage-gated sodium channel activity / CAM型光合成 / Cam-PDE 1 activation ...monoatomic cation homeostasis / positive regulation of synaptic transmission, cholinergic / leak channel activity / regulation of resting membrane potential / viral tegument / cation channel complex / sodium channel activity / voltage-gated sodium channel activity / CAM型光合成 / Cam-PDE 1 activation / Sodium/Calcium exchangers / 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 / monoatomic ion channel complex / CaMK IV-mediated phosphorylation of CREB / Glycogen breakdown (glycogenolysis) / organelle localization by membrane tethering / negative regulation of calcium ion export across plasma membrane / Activation of RAC1 downstream of NMDARs / mitochondrion-endoplasmic reticulum membrane tethering / CLEC7A (Dectin-1) induces NFAT activation / regulation of cardiac muscle cell action potential / autophagosome membrane docking / positive regulation of ryanodine-sensitive calcium-release channel activity / Negative regulation of NMDA receptor-mediated neuronal transmission / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-threonine phosphorylation / Unblocking of NMDA receptors, glutamate binding and activation / Synthesis of IP3 and IP4 in the cytosol / Phase 0 - rapid depolarisation / protein phosphatase activator activity / RHO GTPases activate PAKs / positive regulation of cyclic-nucleotide phosphodiesterase activity / positive regulation of phosphoprotein phosphatase activity / Ion transport by P-type ATPases / 長期増強 / calcium ion import across plasma membrane / Uptake and function of anthrax toxins / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / catalytic complex / DARPP-32 events / detection of calcium ion / sodium ion transmembrane transport / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction / calcium channel inhibitor activity / cellular response to interferon-beta / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Protein methylation / voltage-gated potassium channel complex / eNOS activation / Activation of AMPK downstream of NMDARs / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / positive regulation of protein dephosphorylation / regulation of calcium-mediated signaling / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / monoatomic cation channel activity / Ion homeostasis / titin binding / regulation of ryanodine-sensitive calcium-release channel activity / positive regulation of protein autophosphorylation / 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 / monoatomic ion transmembrane transport / protein serine/threonine kinase activator activity / sarcomere / FCERI mediated Ca+2 mobilization / 生物発光 / FCGR3A-mediated IL10 synthesis / VEGFR2 mediated vascular permeability / regulation of cytokinesis / positive regulation of peptidyl-threonine phosphorylation / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / VEGFR2 mediated cell proliferation / generation of precursor metabolites and energy / Translocation of SLC2A4 (GLUT4) to the plasma membrane / positive regulation of synaptic transmission, GABAergic / calcium ion transmembrane transport / RAF activation / positive regulation of receptor signaling pathway via JAK-STAT / spindle microtubule / Transcriptional activation of mitochondrial biogenesis / positive regulation of protein serine/threonine kinase activity / Stimuli-sensing channels / 紡錘体 / cellular response to type II interferon 類似検索 - 分子機能 | ||||||
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: 4.5 Å | ||||||
データ登録者 | Wu, J.P. / Yan, Z. / Zhou, L. / Liu, H. / Zhao, Q. | ||||||
資金援助 | 1件
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引用 | ジャーナル: Cell Discov / 年: 2022 タイトル: Architecture of the human NALCN channelosome. 著者: Lunni Zhou / Haobin Liu / Qingqing Zhao / Jianping Wu / Zhen Yan / 要旨: NALCN regulates the resting membrane potential by mediating the Na leak current in neurons, and it functions as a channelosome in complex with FAM155A, UNC79, and UNC80. Dysfunction of the NALCN ...NALCN regulates the resting membrane potential by mediating the Na leak current in neurons, and it functions as a channelosome in complex with FAM155A, UNC79, and UNC80. Dysfunction of the NALCN channelosome causes a broad range of neurological and developmental diseases called NALCN channelopathies in humans. How the auxiliary subunits, especially the two large components UNC79 and UNC80, assemble with NALCN and regulate its function remains unclear. Here we report an overall architecture of the human NALCN channelosome. UNC79 and UNC80 each adopt an S-shape super-helical structure consisting of HEAT and armadillo repeats, forming a super-coiled heterodimeric assembly in the cytoplasmic side, which may provide a scaffold for the binding of other potential modulators of the channelosome. The UNC79-UNC80 assembly specifically associates with the NALCN-FAM155A subcomplex through the intracellular II-III linker of NALCN. Disruptions of the interaction interfaces between UNC79 and UNC80, and between the II-III linker of NALCN and the UNC79-UNC80 assembly, significantly reduce the NALCN-mediated currents in HEK293T system, suggesting the importance of the UNC79-UNC80 assembly in regulating channelosome function. Cross-linking mass spectrometry analysis identified an additional calmodulin (CaM) bound in the carboxyl-terminal domain of NALCN. Our study thus provides a structural basis for understanding the unique assembly mechanism and functional regulation of the NALCN channelosome, and also provides an opportunity for the interpretation of many disease-related mutations in UNC80. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7wji.cif.gz | 963.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7wji.ent.gz | 767.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7wji.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/wj/7wji ftp://data.pdbj.org/pub/pdb/validation_reports/wj/7wji | HTTPS FTP |
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-関連構造データ
関連構造データ | 32544MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 363856.188 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: UNC80, C2orf21, KIAA1843 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q8N2C7 |
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#2: タンパク質 | 分子量: 298239.656 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: UNC79, KIAA1409 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q9P2D8 |
#3: タンパク質 | 分子量: 16852.545 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CALM1, CALM, CAM, CAM1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P0DP23 |
#4: タンパク質 | 分子量: 229017.703 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NALCN, VGCNL1, UL32 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q8IZF0, UniProt: A0A076JQ90 |
#5: タンパク質 | 分子量: 51550.484 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: FAM155A / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: B1AL88 |
-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 |
-試料調製
構成要素 | 名称: NALCN channelosome / タイプ: COMPLEX / 詳細: NALCN-FAM155A-UNC79-UNC80-CaM / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 値: 0.9 MDa / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.4 |
試料 | 濃度: 0.1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
急速凍結 | 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 281 K |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy / 倍率(公称値): 81000 X / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 1400 nm / Cs: 2.7 mm |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
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) |
-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: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 4.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 174294 / アルゴリズム: FOURIER SPACE / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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