登録情報 データベース : EMDB / ID : EMD-30067 構造の表示 ダウンロードとリンクタイトル Structure of RyR1 (Ca2+/Caffeine/ATP/CaM1234/CHL) マップデータRyR1 Ca2 /ATP/caffeine/CaM1234/CHL 詳細 試料複合体 : RyR1 Ca2 /ATP/caffeine/CaM1234/CHL複合体 : RyR1タンパク質・ペプチド : Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1,Ryanodine receptor 1複合体 : FKBP12.6 and CAM1234タンパク質・ペプチド : Peptidyl-prolyl cis-trans isomerase FKBP1Bタンパク質・ペプチド : Calmodulin-1リガンド : CAFFEINEリガンド : CALCIUM IONリガンド : ADENOSINE-5'-TRIPHOSPHATEリガンド : ZINC IONリガンド : 5-bromanyl-N-[4-chloranyl-2-methyl-6-(methylcarbamoyl)phenyl]-2-(3-chloranylpyridin-2-yl)pyrazole-3-carboxamide 残り2件を表示 表示を減らす 詳細 キーワード Rabbit / Ryanodine receptor1 / CHL. / MEMBRANE PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / negative regulation of calcium-mediated signaling / negative regulation of insulin secretion involved in cellular response to glucose stimulus / neuronal action potential propagation / negative regulation of release of sequestered calcium ion into cytosol / insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity ... ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / negative regulation of calcium-mediated signaling / negative regulation of insulin secretion involved in cellular response to glucose stimulus / neuronal action potential propagation / negative regulation of release of sequestered calcium ion into cytosol / insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / CaM pathway / Cam-PDE 1 activation / Sodium/Calcium exchangers / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / Calmodulin induced events / response to redox state / Reduction of cytosolic Ca++ levels / ossification involved in bone maturation / Activation of Ca-permeable Kainate Receptor / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Loss of phosphorylation of MECP2 at T308 / 'de novo' protein folding / cellular response to caffeine / CREB1 phosphorylation through the activation of Adenylate Cyclase / negative regulation of heart rate / CaMK IV-mediated phosphorylation of CREB / PKA activation / negative regulation of high voltage-gated calcium channel activity / Glycogen breakdown (glycogenolysis) / skin development / CLEC7A (Dectin-1) induces NFAT activation / Activation of RAC1 downstream of NMDARs / negative regulation of ryanodine-sensitive calcium-release channel activity / organelle localization by membrane tethering / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / FK506 binding / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / presynaptic endocytosis / organelle membrane / Synthesis of IP3 and IP4 in the cytosol / regulation of cell communication by electrical coupling involved in cardiac conduction / Phase 0 - rapid depolarisation / calcineurin-mediated signaling / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / RHO GTPases activate PAKs / smooth endoplasmic reticulum / intracellularly gated calcium channel activity / outflow tract morphogenesis / Ion transport by P-type ATPases / Uptake and function of anthrax toxins / regulation of ryanodine-sensitive calcium-release channel activity / Long-term potentiation / protein phosphatase activator activity / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / smooth muscle contraction / DARPP-32 events / catalytic complex / Smooth Muscle Contraction / detection of calcium ion / regulation of cardiac muscle contraction / RHO GTPases activate IQGAPs / toxic substance binding / T cell proliferation / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / striated muscle contraction / voltage-gated calcium channel activity / cellular response to interferon-beta / Protein methylation / calcium channel inhibitor activity / Activation of AMPK downstream of NMDARs / presynaptic cytosol / skeletal muscle fiber development / Ion homeostasis / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / eNOS activation / titin binding / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / sperm midpiece / release of sequestered calcium ion into cytosol / regulation of calcium-mediated signaling / voltage-gated potassium channel complex / calcium channel complex / substantia nigra development / FCERI mediated Ca+2 mobilization / sarcoplasmic reticulum membrane / Ras activation upon Ca2+ influx through NMDA receptor / muscle contraction / regulation of heart rate / FCGR3A-mediated IL10 synthesis / cellular response to calcium ion / calyx of Held / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / adenylate cyclase activator activity / sarcoplasmic reticulum / protein maturation / sarcomere 類似検索 - 分子機能 Ryanodine receptor, SPRY domain 2 / : / Ryanodine receptor junctional solenoid repeat / Ryanodine Receptor TM 4-6 / Ryanodine receptor / Ryanodine receptor, SPRY domain 1 / Ryanodine receptor, SPRY domain 3 / Ryanodine Receptor TM 4-6 / Ryanodine receptor Ryr / RyR domain ... Ryanodine receptor, SPRY domain 2 / : / Ryanodine receptor junctional solenoid repeat / Ryanodine Receptor TM 4-6 / Ryanodine receptor / Ryanodine receptor, SPRY domain 1 / Ryanodine receptor, SPRY domain 3 / Ryanodine Receptor TM 4-6 / Ryanodine receptor Ryr / RyR domain / : / RyR/IP3 receptor binding core, RIH domain superfamily / RyR/IP3R Homology associated domain / Inositol 1,4,5-trisphosphate/ryanodine receptor / RIH domain / RyR and IP3R Homology associated / Inositol 1,4,5-trisphosphate/ryanodine receptor / RIH domain / : / MIR motif / MIR domain / MIR domain profile. / Domain in ryanodine and inositol trisphosphate receptors and protein O-mannosyltransferases / Mir domain superfamily / SPRY domain / B30.2/SPRY domain / B30.2/SPRY domain profile. / B30.2/SPRY domain superfamily / Domain in SPla and the RYanodine Receptor. / SPRY domain / FKBP-type peptidyl-prolyl cis-trans isomerase / FKBP-type peptidyl-prolyl cis-trans isomerase domain / FKBP-type peptidyl-prolyl cis-trans isomerase domain profile. / Peptidyl-prolyl cis-trans isomerase domain superfamily / : / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / Ion transport domain / Ion transport protein / EF-hand domain pair / Concanavalin A-like lectin/glucanase domain superfamily 類似検索 - ドメイン・相同性 Calmodulin-1 / Ryanodine receptor 1 / Peptidyl-prolyl cis-trans isomerase FKBP1B 類似検索 - 構成要素生物種 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 詳細 データ登録者Ma R / Haji-Ghassemi O 資金援助 中国, カナダ, 4件 詳細 詳細を隠すOrganization Grant number 国 National Natural Science Foundation of China (NSFC) 31972287 中国 Ministry of Science and Technology (MoST, China) 2017YFD0201400 中国 Ministry of Science and Technology (MoST, China) 2017YFD0201403 中国 Canadian Institutes of Health Research (CIHR) PJT-159601 カナダ
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 登録 2020年3月1日 - ヘッダ(付随情報) 公開 2020年9月2日 - マップ公開 2020年9月2日 - 更新 2024年3月27日 - 現状 2024年3月27日 処理サイト : PDBj / 状態 : 公開
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