+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-35883 | |||||||||||||||
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タイトル | Human KCNQ2-CaM-HN37 complex in the presence of PIP2 | |||||||||||||||
マップデータ | ||||||||||||||||
試料 |
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キーワード | potassium voltage-gated channel / HN37 / MEMBRANE PROTEIN | |||||||||||||||
機能・相同性 | 機能・相同性情報 axon initial segment / node of Ranvier / Voltage gated Potassium channels / voltage-gated monoatomic cation channel activity / CaM pathway / Cam-PDE 1 activation / Interaction between L1 and Ankyrins / Sodium/Calcium exchangers / Reduction of cytosolic Ca++ levels / Calmodulin induced events ...axon initial segment / node of Ranvier / Voltage gated Potassium channels / voltage-gated monoatomic cation channel activity / CaM pathway / Cam-PDE 1 activation / Interaction between L1 and Ankyrins / Sodium/Calcium exchangers / Reduction of cytosolic Ca++ levels / Calmodulin induced events / 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 / ankyrin binding / organelle localization by membrane tethering / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / autophagosome membrane docking / mitochondrion-endoplasmic reticulum membrane tethering / Glycogen breakdown (glycogenolysis) / positive regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of calcium ion export across plasma membrane / CLEC7A (Dectin-1) induces NFAT activation / Activation of RAC1 downstream of NMDARs / regulation of cardiac muscle cell action potential / action potential / positive regulation of ryanodine-sensitive calcium-release channel activity / regulation of cell communication by electrical coupling involved in cardiac conduction / Synthesis of IP3 and IP4 in the cytosol / negative regulation of peptidyl-threonine phosphorylation / Negative regulation of NMDA receptor-mediated neuronal transmission / Phase 0 - rapid depolarisation / Unblocking of NMDA receptors, glutamate binding and activation / negative regulation of ryanodine-sensitive calcium-release channel activity / adenylate cyclase activator activity / protein phosphatase activator activity / RHO GTPases activate PAKs / Ion transport by P-type ATPases / : / Uptake and function of anthrax toxins / Long-term potentiation / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / voltage-gated potassium channel activity / catalytic complex / DARPP-32 events / regulation of cardiac muscle contraction / detection of calcium ion / Smooth Muscle Contraction / regulation of ryanodine-sensitive calcium-release channel activity / cellular response to interferon-beta / RHO GTPases activate IQGAPs / calcium channel inhibitor activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / eNOS activation / Protein methylation / voltage-gated potassium channel complex / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Activation of AMPK downstream of NMDARs / Ion homeostasis / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / : / titin binding / positive regulation of protein autophosphorylation / regulation of calcium-mediated signaling / sperm midpiece / potassium ion transmembrane transport / calcium channel complex / substantia nigra development / Ras activation upon Ca2+ influx through NMDA receptor / sarcomere / regulation of heart rate / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / protein serine/threonine kinase activator activity / VEGFR2 mediated vascular permeability / regulation of cytokinesis / VEGFR2 mediated cell proliferation / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / positive regulation of peptidyl-threonine phosphorylation / spindle microtubule / Translocation of SLC2A4 (GLUT4) to the plasma membrane / positive regulation of receptor signaling pathway via JAK-STAT / RAF activation / Transcriptional activation of mitochondrial biogenesis / positive regulation of protein serine/threonine kinase activity / Stimuli-sensing channels / cellular response to type II interferon / spindle pole / response to calcium ion / RAS processing / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / calcium-dependent protein binding / G2/M transition of mitotic cell cycle / Signaling by BRAF and RAF1 fusions 類似検索 - 分子機能 | |||||||||||||||
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: 2.7 Å | |||||||||||||||
データ登録者 | Ma D / Li X / Guo J | |||||||||||||||
資金援助 | 中国, 4件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Ligand activation mechanisms of human KCNQ2 channel. 著者: Demin Ma / Yueming Zheng / Xiaoxiao Li / Xiaoyu Zhou / Zhenni Yang / Yan Zhang / Long Wang / Wenbo Zhang / Jiajia Fang / Guohua Zhao / Panpan Hou / Fajun Nan / Wei Yang / Nannan Su / Zhaobing ...著者: Demin Ma / Yueming Zheng / Xiaoxiao Li / Xiaoyu Zhou / Zhenni Yang / Yan Zhang / Long Wang / Wenbo Zhang / Jiajia Fang / Guohua Zhao / Panpan Hou / Fajun Nan / Wei Yang / Nannan Su / Zhaobing Gao / Jiangtao Guo / 要旨: The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but ...The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP, and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2. | |||||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_35883.map.gz | 48.2 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-35883-v30.xml emd-35883.xml | 16.3 KB 16.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_35883.png | 69.8 KB | ||
Filedesc metadata | emd-35883.cif.gz | 5.9 KB | ||
その他 | emd_35883_half_map_1.map.gz emd_35883_half_map_2.map.gz | 37.1 MB 37.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-35883 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35883 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_35883_validation.pdf.gz | 789.7 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_35883_full_validation.pdf.gz | 789.3 KB | 表示 | |
XML形式データ | emd_35883_validation.xml.gz | 11.7 KB | 表示 | |
CIF形式データ | emd_35883_validation.cif.gz | 13.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35883 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35883 | HTTPS FTP |
-関連構造データ
関連構造データ | 8j04MC 8izyC 8j00C 8j01C 8j02C 8j03C 8j05C 8w4uC M: このマップから作成された原子モデル 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
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_35883.map.gz / 形式: CCP4 / 大きさ: 52.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.93 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
ファイル | emd_35883_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_35883_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Human KCNQ2-CaM-HN37 complex in the presence of PIP2
全体 | 名称: Human KCNQ2-CaM-HN37 complex in the presence of PIP2 |
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要素 |
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-超分子 #1: Human KCNQ2-CaM-HN37 complex in the presence of PIP2
超分子 | 名称: Human KCNQ2-CaM-HN37 complex in the presence of PIP2 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Potassium voltage-gated channel subfamily KQT member 2
分子 | 名称: Potassium voltage-gated channel subfamily KQT member 2 タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 73.627812 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MAGKPPKRNA FYRKLQNFLY NVLERPRGWA FIYHAYVFLL VFSCLVLSVF STIKEYEKSS EGALYILEIV TIVVFGVEYF VRIWAAGCC CRYRGWRGRL KFARKPFCVI DIMVLIASIA VLAAGSQGNV FATSALRSLR FLQILRMIRM DRRGGTWKLL G SVVYAHSK ...文字列: MAGKPPKRNA FYRKLQNFLY NVLERPRGWA FIYHAYVFLL VFSCLVLSVF STIKEYEKSS EGALYILEIV TIVVFGVEYF VRIWAAGCC CRYRGWRGRL KFARKPFCVI DIMVLIASIA VLAAGSQGNV FATSALRSLR FLQILRMIRM DRRGGTWKLL G SVVYAHSK ELVTAWYIGF LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI GV SFFALPA GILGSGFALK VQEQHRQKHF EKRRNPAAGL IQSAWRFYAT NLSRTDLHST WQYYERTVTV PMYSSQTQTY GAS RLIPPL NQLELLRNLK SKSGLAFRKD PPPEPSPSKG SPCRGPLCGC CPGRSSQKVS LKDRVFSSPR GVAAKGKGSP QAQT VRRSP SADQSLEDSP SKVPKSWSFG DRSRARQAFR IKGAASRQNS EEASLPGEDI VDDKSCPCEF VTEDLTPGLK VSIRA VCVM RFLVSKRKFK ESLRPYDVMD VIEQYSAGHL DMLSRIKSLQ SRVDQIVGRG PAITDKDRTK GPAEAELPED PSMMGR LGK VEKQVLSMEK KLDFLVNIYM QRMGIPPTET EAYFGAKEPE PAPPYHSPED SREHVDRHGC IVKIVRSSSS TGQKNFS VE GGSSGGWSHP QFEK UniProtKB: Potassium voltage-gated channel subfamily KQT member 2 |
-分子 #2: Calmodulin-1
分子 | 名称: Calmodulin-1 / タイプ: protein_or_peptide / ID: 2 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 19.615445 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG NGTIDFPEFL TMMARKMKDT DSEEEIREA FRVFDKDGNG YISAAELRHV MTNLGEKLTD EEVDEMIREA DIDGDGQVNY EEFVQMMTAK LEGGSSGGLV P RGSGGSSG GHHHHHHHH UniProtKB: Calmodulin-1 |
-分子 #3: methyl N-[4-[(4-fluorophenyl)methyl-prop-2-ynyl-amino]-2,6-dimeth...
分子 | 名称: methyl N-[4-[(4-fluorophenyl)methyl-prop-2-ynyl-amino]-2,6-dimethyl-phenyl]carbamate タイプ: ligand / ID: 3 / コピー数: 8 / 式: 9MF |
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分子量 | 理論値: 340.391 Da |
Chemical component information | ChemComp-9MF: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 8 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 52.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1.5 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 146702 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |