+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-26205 | |||||||||||||||||||||
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タイトル | A drug and ATP binding site in type 1 ryanodine receptor | |||||||||||||||||||||
マップデータ | Composite map | |||||||||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 cytoplasmic side of membrane / ATP-gated ion channel activity / terminal cisterna / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / ossification involved in bone maturation ...cytoplasmic side of membrane / ATP-gated ion channel activity / terminal cisterna / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / ossification involved in bone maturation / 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 / skin development / 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 / regulation of cardiac muscle cell action potential / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / Activation of RAC1 downstream of NMDARs / 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 / cellular response to caffeine / negative regulation of peptidyl-threonine phosphorylation / Synthesis of IP3 and IP4 in the cytosol / Unblocking of NMDA receptors, glutamate binding and activation / outflow tract morphogenesis / Phase 0 - rapid depolarisation / intracellularly gated calcium channel activity / protein phosphatase activator activity / RHO GTPases activate PAKs / organelle membrane / positive regulation of phosphoprotein phosphatase activity / Ion transport by P-type ATPases / Long-term potentiation / Uptake and function of anthrax toxins / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / catalytic complex / DARPP-32 events / detection of calcium ion / regulation of cardiac muscle contraction / toxic substance binding / smooth endoplasmic reticulum / negative regulation of ryanodine-sensitive calcium-release channel activity / Smooth Muscle Contraction / voltage-gated calcium channel activity / calcium channel inhibitor activity / RHO GTPases activate IQGAPs / cellular response to interferon-beta / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / Protein methylation / eNOS activation / skeletal muscle fiber development / striated muscle contraction / Activation of AMPK downstream of NMDARs / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / release of sequestered calcium ion into cytosol / 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 / sperm midpiece / sarcoplasmic reticulum membrane / calcium channel complex / cellular response to calcium ion / 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 / regulation of cytokinesis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / positive regulation of peptidyl-threonine phosphorylation / VEGFR2 mediated cell proliferation / peptidylprolyl isomerase / sarcoplasmic reticulum / peptidyl-prolyl cis-trans isomerase activity / muscle contraction / Translocation of SLC2A4 (GLUT4) to the plasma membrane / calcium ion transmembrane transport / positive regulation of receptor signaling pathway via JAK-STAT 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | Oryctolagus cuniculus (ウサギ) / Homo sapiens (ヒト) / rabbit (ウサギ) | |||||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.45 Å | |||||||||||||||||||||
データ登録者 | Melville Z / Dridi H / Yuan Q / Reiken S / Anetta W / Liu Y / Clarke OB / Marks AR | |||||||||||||||||||||
資金援助 | 米国, 6件
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引用 | ジャーナル: Structure / 年: 2022 タイトル: A drug and ATP binding site in type 1 ryanodine receptor. 著者: Zephan Melville / Haikel Dridi / Qi Yuan / Steven Reiken / Anetta Wronska / Yang Liu / Oliver B Clarke / Andrew R Marks / 要旨: The ryanodine receptor (RyR)/calcium release channel on the sarcoplasmic reticulum (SR) is required for excitation-contraction coupling in skeletal and cardiac muscle. Inherited mutations and stress- ...The ryanodine receptor (RyR)/calcium release channel on the sarcoplasmic reticulum (SR) is required for excitation-contraction coupling in skeletal and cardiac muscle. Inherited mutations and stress-induced post-translational modifications result in an SR Ca leak that causes skeletal myopathies, heart failure, and exercise-induced sudden death. A class of therapeutics known as Rycals prevent the RyR-mediated leak, are effective in preventing disease progression and restoring function in animal models, and are in clinical trials for patients with muscle and heart disorders. Using cryogenic-electron microscopy, we present a model of RyR1 with a 2.45-Å resolution before local refinement, revealing a binding site in the RY1&2 domain (3.10 Å local resolution), where the Rycal ARM210 binds cooperatively with ATP and stabilizes the closed state of RyR1. | |||||||||||||||||||||
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_26205.map.gz | 379.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-26205-v30.xml emd-26205.xml | 32 KB 32 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_26205_fsc.xml emd_26205_fsc_2.xml | 19.1 KB 19 KB | 表示 表示 | FSCデータファイル |
画像 | emd_26205.png | 81.3 KB | ||
マスクデータ | emd_26205_msk_1.map emd_26205_msk_2.map emd_26205_msk_3.map | 512 MB 512 MB 512 MB | マスクマップ | |
その他 | emd_26205_additional_1.map.gz emd_26205_half_map_1.map.gz emd_26205_half_map_2.map.gz | 256.4 MB 391.7 MB 391.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26205 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26205 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_26205_validation.pdf.gz | 936.5 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_26205_full_validation.pdf.gz | 936.1 KB | 表示 | |
XML形式データ | emd_26205_validation.xml.gz | 26 KB | 表示 | |
CIF形式データ | emd_26205_validation.cif.gz | 34.3 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26205 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26205 | HTTPS FTP |
-関連構造データ
関連構造データ | 7tzcMC 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 |
電子顕微鏡画像生データ | EMPIAR-10997 (タイトル: A drug and ATP binding site in type 1 ryanodine receptor Data size: 1.5 TB Data #1: Type-1 ryanodine receptor [micrographs - multiframe]) |
-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_26205.map.gz / 形式: CCP4 / 大きさ: 512 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Composite map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.833 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
-マスク #1
ファイル | emd_26205_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-マスク #2
ファイル | emd_26205_msk_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-マスク #3
ファイル | emd_26205_msk_3.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Initial refinement map
ファイル | emd_26205_additional_1.map | ||||||||||||
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注釈 | Initial refinement map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_26205_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_26205_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 : Ryanodine receptor 1 complex with calmodulin and calstabin-1
+超分子 #1: Ryanodine receptor 1 complex with calmodulin and calstabin-1
+分子 #1: Calmodulin-1
+分子 #2: Peptidyl-prolyl cis-trans isomerase FKBP1A
+分子 #3: Ryanodine receptor 1
+分子 #4: CALCIUM ION
+分子 #5: ADENOSINE-5'-TRIPHOSPHATE
+分子 #6: ZINC ION
+分子 #7: CAFFEINE
+分子 #8: 4-[(7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)methyl]benz...
+分子 #9: (2S)-3-(octadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
-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 | 8.4 mg/mL | |||||||||||||||||||||||||||
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緩衝液 | pH: 7.5 構成要素:
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グリッド | モデル: Quantifoil R0.6/1 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY / 支持フィルム - Film thickness: 50.0 nm | |||||||||||||||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 4 K / 装置: FEI VITROBOT MARK IV |
-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: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 6862 / 平均露光時間: 2.5 sec. / 平均電子線量: 57.65 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 100.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 1.0 µm / 倍率(公称値): 105000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |