+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-8712 | |||||||||
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タイトル | CryoEM structure of Xenopus KCNQ1 channel | |||||||||
マップデータ | Xenopus KCNQ1 channel, unsharpened map | |||||||||
試料 |
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キーワード | KCNQ1-CaM complex / potassium channel / Long QT syndrome / TRANSPORT PROTEIN / CALCIUM BINDING PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 regulation of gastric acid secretion / membrane repolarization / : / establishment of protein localization to mitochondrial membrane / delayed rectifier potassium channel activity / type 3 metabotropic glutamate receptor binding / outward rectifier potassium channel activity / CaM pathway / intestinal absorption / Cam-PDE 1 activation ...regulation of gastric acid secretion / membrane repolarization / : / establishment of protein localization to mitochondrial membrane / delayed rectifier potassium channel activity / type 3 metabotropic glutamate receptor binding / outward rectifier potassium channel activity / CaM pathway / intestinal absorption / Cam-PDE 1 activation / Sodium/Calcium exchangers / Reduction of cytosolic Ca++ levels / Calmodulin induced events / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / regulation of synaptic vesicle endocytosis / Activation of Ca-permeable Kainate Receptor / Loss of phosphorylation of MECP2 at T308 / monoatomic ion channel complex / CREB1 phosphorylation through the activation of Adenylate Cyclase / PKA activation / organelle localization by membrane tethering / negative regulation of high voltage-gated calcium channel activity / CaMK IV-mediated phosphorylation of CREB / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / Glycogen breakdown (glycogenolysis) / positive regulation of cyclic-nucleotide phosphodiesterase activity / regulation of synaptic vesicle exocytosis / 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 / response to corticosterone / activation of adenylate cyclase activity / positive regulation of DNA binding / renal absorption / 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 / nitric-oxide synthase binding / 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 / : / inner ear development / Uptake and function of anthrax toxins / Long-term potentiation / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / adenylate cyclase binding / 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 / phosphatidylinositol 3-kinase binding / eNOS activation / Protein methylation / enzyme regulator activity / 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 / calcium channel complex / phosphatidylinositol-4,5-bisphosphate binding / substantia nigra development / nitric-oxide synthase regulator activity / Ras activation upon Ca2+ influx through NMDA receptor / response to amphetamine / sarcomere / regulation of heart rate / FCERI mediated Ca+2 mobilization / protein serine/threonine kinase activator activity / FCGR3A-mediated IL10 synthesis / 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 / positive regulation of nitric-oxide synthase activity / spindle microtubule / Translocation of SLC2A4 (GLUT4) to the plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | Xenopus laevis (アフリカツメガエル) / 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: 3.7 Å | |||||||||
データ登録者 | Mackinnon R / Sun J | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Cell / 年: 2017 タイトル: Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome. 著者: Ji Sun / Roderick MacKinnon / 要旨: KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present ...KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP-free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP. CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP, and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_8712.map.gz | 6.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-8712-v30.xml emd-8712.xml | 14 KB 14 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_8712.png | 126.7 KB | ||
Filedesc metadata | emd-8712.cif.gz | 5.7 KB | ||
その他 | emd_8712_additional.map.gz | 52.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-8712 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8712 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_8712_validation.pdf.gz | 391.4 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_8712_full_validation.pdf.gz | 391 KB | 表示 | |
XML形式データ | emd_8712_validation.xml.gz | 6.1 KB | 表示 | |
CIF形式データ | emd_8712_validation.cif.gz | 6.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8712 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8712 | HTTPS FTP |
-関連構造データ
-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_8712.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Xenopus KCNQ1 channel, unsharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.3 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-追加マップ: Xenopus KCNQ1 channel, sharpened map
ファイル | emd_8712_additional.map | ||||||||||||
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注釈 | Xenopus KCNQ1 channel, sharpened map | ||||||||||||
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 : Complex of Xenopus KCNQ1 and CaM
全体 | 名称: Complex of Xenopus KCNQ1 and CaM |
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要素 |
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-超分子 #1: Complex of Xenopus KCNQ1 and CaM
超分子 | 名称: Complex of Xenopus KCNQ1 and CaM / 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: Xenopus laevis (アフリカツメガエル) |
分子量 | 理論値: 300 KDa |
-分子 #1: Potassium voltage-gated channel subfamily KQT member 1
分子 | 名称: Potassium voltage-gated channel subfamily KQT member 1 タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Xenopus laevis (アフリカツメガエル) |
分子量 | 理論値: 62.663398 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MATDPPRPTI NLDPRVSIYS GRRPLLSRTN IQGRVYNFLE RPTGWKCFVY HFTVFLIVLI CLIFSVLSTI QQYNNLATET LFWMEIVLV VFFGAEYVVR LWSAGCRSKY VGVWGRLRFA RKPISVIDLI VVVASVIVLC VGSNGQVFAT SAIRGIRFLQ I LRMLHVDR ...文字列: MATDPPRPTI NLDPRVSIYS GRRPLLSRTN IQGRVYNFLE RPTGWKCFVY HFTVFLIVLI CLIFSVLSTI QQYNNLATET LFWMEIVLV VFFGAEYVVR LWSAGCRSKY VGVWGRLRFA RKPISVIDLI VVVASVIVLC VGSNGQVFAT SAIRGIRFLQ I LRMLHVDR QGGTWRLLGS VVFIHRQELI TTLYIGFLGL IFSSYFVYLA EKDAIDSSGE YQFGSYADAL WWGVVTVTTI GY GDKVPQT WIGKTIASCF SVFAISFFAL PAGILGSGFA LKVQQKQRQK HFNRQIPAAA SLIQTAWRCY AAENPDSATW KIY IRKQSR NHHLMSPSPK PKKSAMVKKK KIRTERDEGS TDKMLNIPHI TYDHVADDRK NDGYSVESYE NTVRKPFGFL DPST GPFIR TSSFTDDLDM EGDTLLTPIT HISELKEHHR AAIKVIRRMQ YFVAKKKFQQ ARKPYDVRDV IEQYSQGHLN LMVRI KELQ RRLDQSLGKP SLFLSVSDKV KDKGINTIGS RLNRVEDKVT QMDHKLNLIT DMLHHLLTNQ QSNS UniProtKB: Potassium voltage-gated channel subfamily KQT member 1 |
-分子 #2: Calmodulin
分子 | 名称: Calmodulin / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 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: 16.852545 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 UniProtKB: Calmodulin-3 |
-分子 #3: CALCIUM ION
分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 3 / コピー数: 3 / 式: CA |
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分子量 | 理論値: 40.078 Da |
-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
濃度 | 5 mg/mL |
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緩衝液 | pH: 7.2 |
凍結 | 凍結剤: ETHANE / チャンバー内温度: 298 K / 装置: FEI VITROBOT MARK IV / 詳細: 90-100% humidity. |
-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: DIRECT ELECTRON DE-64 (8k x 8k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 1.78 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 |
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: OTHER / 詳細: Generated from 2D class average using EMAN |
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最終 再構成 | 想定した対称性 - 点群: C4 (4回回転対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF ソフトウェア: (名称: RELION (ver. 1.3), FREALIGN (ver. 9.03)) 詳細: Entry was refined using space group P4 and cell parameters a=b=c=332.8 and alpha=beta=gamma=90. 使用した粒子像数: 69415 |
初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |