+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30067 | |||||||||||||||
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タイトル | Structure of RyR1 (Ca2+/Caffeine/ATP/CaM1234/CHL) | |||||||||||||||
マップデータ | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL | |||||||||||||||
試料 |
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キーワード | Rabbit / Ryanodine receptor1 / CHL. / MEMBRANE PROTEIN | |||||||||||||||
機能・相同性 | 機能・相同性情報 ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of calcium-mediated signaling / negative regulation of insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / negative regulation of release of sequestered calcium ion into cytosol / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / neuronal action potential propagation ...ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of calcium-mediated signaling / negative regulation of insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / negative regulation of release of sequestered calcium ion into cytosol / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / CaM pathway / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Cam-PDE 1 activation / Sodium/Calcium exchangers / Reduction of cytosolic Ca++ levels / Calmodulin induced events / ossification involved in bone maturation / response to redox state / protein maturation by protein folding / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Activation of Ca-permeable Kainate Receptor / Loss of phosphorylation of MECP2 at T308 / 'de novo' protein folding / 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 / skin development / negative regulation of heart rate / 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 / FK506 binding / organelle membrane / positive regulation of ryanodine-sensitive calcium-release channel activity / positive regulation of axon regeneration / 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 / cellular response to caffeine / 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 / channel regulator activity / outflow tract morphogenesis / RHO GTPases activate PAKs / Ion transport by P-type ATPases / intracellularly gated calcium channel activity / : / Uptake and function of anthrax toxins / Long-term potentiation / Regulation of MECP2 expression and activity / Calcineurin activates NFAT / catalytic complex / DARPP-32 events / regulation of cardiac muscle contraction / detection of calcium ion / smooth muscle contraction / Smooth Muscle Contraction / response to vitamin E / regulation of ryanodine-sensitive calcium-release channel activity / toxic substance binding / cellular response to interferon-beta / voltage-gated calcium channel activity / smooth endoplasmic reticulum / 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 / skeletal muscle fiber development / T cell proliferation / striated muscle contraction / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Activation of AMPK downstream of NMDARs / Ion homeostasis / muscle contraction / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / : / titin binding / release of sequestered calcium ion into cytosol / positive regulation of protein autophosphorylation / regulation of calcium-mediated signaling / sperm midpiece / regulation of cytosolic calcium ion concentration / sarcoplasmic reticulum membrane / calcium channel complex / substantia nigra development / Ras activation upon Ca2+ influx through NMDA receptor 類似検索 - 分子機能 | |||||||||||||||
生物種 | Oryctolagus cuniculus (ウサギ) / 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: 3.8 Å | |||||||||||||||
データ登録者 | Ma R / Haji-Ghassemi O | |||||||||||||||
資金援助 | 中国, カナダ, 4件
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引用 | ジャーナル: Nat Chem Biol / 年: 2020 タイトル: Structural basis for diamide modulation of ryanodine receptor. 著者: Ruifang Ma / Omid Haji-Ghassemi / Dan Ma / Heng Jiang / Lianyun Lin / Li Yao / Arthur Samurkas / Yuxin Li / Yiwen Wang / Peng Cao / Shian Wu / Yan Zhang / Takashi Murayama / Bernard Moussian ...著者: Ruifang Ma / Omid Haji-Ghassemi / Dan Ma / Heng Jiang / Lianyun Lin / Li Yao / Arthur Samurkas / Yuxin Li / Yiwen Wang / Peng Cao / Shian Wu / Yan Zhang / Takashi Murayama / Bernard Moussian / Filip Van Petegem / Zhiguang Yuchi / 要旨: The diamide insecticide class is one of the top-selling insecticides globally. They are used to control a wide range of pests by targeting their ryanodine receptors (RyRs). Here, we report the ...The diamide insecticide class is one of the top-selling insecticides globally. They are used to control a wide range of pests by targeting their ryanodine receptors (RyRs). Here, we report the highest-resolution cryo-electron microscopy (cryo-EM) structure of RyR1 in the open state, in complex with the anthranilic diamide chlorantraniliprole (CHL). The 3.2-Å local resolution map facilitates unambiguous assignment of the CHL binding site. The molecule induces a conformational change by affecting the S4-S5 linker, triggering channel opening. The binding site is further corroborated by mutagenesis data, which reveal how diamide insecticides are selective to the Lepidoptera group of insects over honeybee or mammalian RyRs. Our data reveal that several pests have developed resistance via two mechanisms, steric hindrance and loss of contact. Our results provide a foundation for the development of highly selective pesticides aimed at overcoming resistance and therapeutic molecules to treat human myopathies. | |||||||||||||||
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_30067.map.gz | 33.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-30067-v30.xml emd-30067.xml | 31.1 KB 31.1 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_30067_fsc.xml | 15.9 KB | 表示 | FSCデータファイル |
画像 | emd_30067.png | 336.2 KB | ||
Filedesc metadata | emd-30067.cif.gz | 9.1 KB | ||
その他 | emd_30067_additional.map.gz emd_30067_additional_1.map.gz emd_30067_half_map_1.map.gz emd_30067_half_map_2.map.gz | 79.2 MB 79.2 MB 267.8 MB 267.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30067 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30067 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_30067_validation.pdf.gz | 851.4 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_30067_full_validation.pdf.gz | 850.9 KB | 表示 | |
XML形式データ | emd_30067_validation.xml.gz | 23.5 KB | 表示 | |
CIF形式データ | emd_30067_validation.cif.gz | 31 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30067 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30067 | 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_30067.map.gz / 形式: CCP4 / 大きさ: 343 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.08 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: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified
ファイル | emd_30067_additional.map | ||||||||||||
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注釈 | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified
ファイル | emd_30067_additional_1.map | ||||||||||||
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注釈 | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL,density modified | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half map
ファイル | emd_30067_half_map_1.map | ||||||||||||
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注釈 | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half 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: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half map
ファイル | emd_30067_half_map_2.map | ||||||||||||
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注釈 | RyR1 Ca2 /ATP/caffeine/CaM1234/CHL, half 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 : RyR1 Ca2 /ATP/caffeine/CaM1234/CHL
+超分子 #1: RyR1 Ca2 /ATP/caffeine/CaM1234/CHL
+超分子 #2: RyR1
+超分子 #3: FKBP12.6 and CAM1234
+分子 #1: Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1,Ry...
+分子 #2: Peptidyl-prolyl cis-trans isomerase FKBP1B
+分子 #3: Calmodulin-1
+分子 #4: CAFFEINE
+分子 #5: CALCIUM ION
+分子 #6: ADENOSINE-5'-TRIPHOSPHATE
+分子 #7: ZINC ION
+分子 #8: 5-bromanyl-N-[4-chloranyl-2-methyl-6-(methylcarbamoyl)phenyl]-2-(...
-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: 7.5 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON III (4k x 4k) 平均電子線量: 50.0 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 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |