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基本情報
登録情報 | データベース: PDB / ID: 7cf9 | |||||||||||||||
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タイトル | Structure of RyR1 (Ca2+/CHL) | |||||||||||||||
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![]() | MEMBRANE PROTEIN / Rabbit / Ryanodine receptor1 / CHL. | |||||||||||||||
機能・相同性 | ![]() ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / ryanodine receptor complex / negative regulation of release of sequestered calcium ion into cytosol / ryanodine-sensitive calcium-release channel activity / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus ...ATP-gated ion channel activity / positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / terminal cisterna / ryanodine receptor complex / negative regulation of release of sequestered calcium ion into cytosol / ryanodine-sensitive calcium-release channel activity / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / ossification involved in bone maturation / cell communication by electrical coupling involved in cardiac conduction / response to redox state / protein maturation by protein folding / 'de novo' protein folding / skin development / negative regulation of heart rate / negative regulation of phosphoprotein phosphatase activity / FK506 binding / positive regulation of axon regeneration / cellular response to caffeine / outflow tract morphogenesis / intracellularly gated calcium channel activity / organelle membrane / : / smooth muscle contraction / toxic substance binding / smooth endoplasmic reticulum / negative regulation of ryanodine-sensitive calcium-release channel activity / voltage-gated calcium channel activity / response to vitamin E / calcium channel inhibitor activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / protein peptidyl-prolyl isomerization / skeletal muscle fiber development / T cell proliferation / striated muscle contraction / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / release of sequestered calcium ion into cytosol / Ion homeostasis / regulation of ryanodine-sensitive calcium-release channel activity / sarcoplasmic reticulum membrane / calcium channel complex / regulation of cytosolic calcium ion concentration / cellular response to calcium ion / peptidylprolyl isomerase / sarcoplasmic reticulum / peptidyl-prolyl cis-trans isomerase activity / muscle contraction / calcium ion transmembrane transport / calcium channel activity / response to hydrogen peroxide / Stimuli-sensing channels / sarcolemma / Z disc / intracellular calcium ion homeostasis / disordered domain specific binding / positive regulation of cytosolic calcium ion concentration / protein refolding / protein homotetramerization / transmembrane transporter binding / calmodulin binding / signaling receptor binding / calcium ion binding / ATP binding / identical protein binding / membrane / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||||||||
生物種 | ![]() ![]() ![]() | |||||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.7 Å | |||||||||||||||
![]() | Ma, R. / Haji-Ghassemi, O. / Ma, D. / Lin, L. / Samurkas, A. / Van Petegem, F. / Yuchi, Z. | |||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() 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. | |||||||||||||||
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要素
#1: タンパク質 | 分子量: 539836.938 Da / 分子数: 4 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #2: タンパク質 | 分子量: 11667.305 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #3: 化合物 | ChemComp-CA / #4: 化合物 | ChemComp-ZN / #5: 化合物 | ChemComp-F0U / 研究の焦点であるリガンドがあるか | Y | 配列の詳細 | Complete sequence of RyR1 protein is: ...Complete sequence of RyR1 protein is: MGDGGEGEDE | |
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