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基本情報
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タイトル | Cryo-EM structure of Coxsackievirus B1 muture virion in complex with nAbs 8A10 and 5F5 (CVB1-M:8A10:5F5) | |||||||||
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機能・相同性 | ![]() symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression ...symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / DNA replication / host cell cytoplasm / RNA helicase activity / symbiont entry into host cell / induction by virus of host autophagy / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / DNA-templated transcription / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.03 Å | |||||||||
![]() | Zheng Q / Zhu R / Sun H / Cheng T / Li S / Xia N | |||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail. 著者: Qingbing Zheng / Rui Zhu / Zhichao Yin / Longfa Xu / Hui Sun / Hai Yu / Yuanyuan Wu / Yichao Jiang / Qiongzi Huang / Yang Huang / Dongqing Zhang / Liqin Liu / Hongwei Yang / Maozhou He / ...著者: Qingbing Zheng / Rui Zhu / Zhichao Yin / Longfa Xu / Hui Sun / Hai Yu / Yuanyuan Wu / Yichao Jiang / Qiongzi Huang / Yang Huang / Dongqing Zhang / Liqin Liu / Hongwei Yang / Maozhou He / Zhenhong Zhou / Yanan Jiang / Zhenqin Chen / Huan Zhao / Yuqiong Que / Zhibo Kong / Lizhi Zhou / Tingting Li / Jun Zhang / Wenxin Luo / Ying Gu / Tong Cheng / Shaowei Li / Ningshao Xia / ![]() 要旨: Coxsackievirus B1 (CVB1) is an emerging pathogen associated with severe neonatal diseases including aseptic meningitis, myocarditis, and pancreatitis and also with the development of type 1 diabetes. ...Coxsackievirus B1 (CVB1) is an emerging pathogen associated with severe neonatal diseases including aseptic meningitis, myocarditis, and pancreatitis and also with the development of type 1 diabetes. We characterize the binding and therapeutic efficacies of three CVB1-specific neutralizing antibodies (nAbs) identified for their ability to inhibit host receptor engagement. High-resolution cryo-EM structures showed that these antibodies recognize different epitopes but with an overlapping region in the capsid VP2 protein and specifically the highly variable EF loop. Moreover, they perturb capsid-receptor interactions by binding various viral particle forms. Antibody combinations achieve synergetic neutralization via a stepwise capsid transition and virion disruption, indicating dynamic changes in the virion in response to multiple nAbs targeting the receptor-binding site. Furthermore, this three-antibody cocktail protects against lethal challenge in neonatal mice and limits pancreatitis and viral replication in a non-obese diabetic mouse model. These results illustrate the utility of nAbs for rational design of therapeutics against picornaviruses such as CVB. | |||||||||
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マップデータ | ![]() | 631.6 MB | ![]() | |
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画像 | ![]() | 85.2 KB | ||
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関連構造データ | ![]() 7x3cMC ![]() 7x2gC ![]() 7x2iC ![]() 7x2oC ![]() 7x2tC ![]() 7x2wC ![]() 7x35C ![]() 7x37C ![]() 7x38C ![]() 7x3dC ![]() 7x3eC ![]() 7x3fC ![]() 7x3yC ![]() 7x40C ![]() 7x42C ![]() 7x46C ![]() 7x47C ![]() 7x49C ![]() 7x4kC ![]() 7x4mC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.12 Å | ||||||||||||||||||||
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
+全体 : Cryo-EM structure of Coxsackievirus B1 muture virion in complex w...
+超分子 #1: Cryo-EM structure of Coxsackievirus B1 muture virion in complex w...
+分子 #1: 8A10 light chain
+分子 #2: 8A10 heavy chain
+分子 #3: Virion protein 1
+分子 #4: VP2
+分子 #5: VP3
+分子 #6: Capsid protein VP4
+分子 #7: 5F5 light chain
+分子 #8: 5F5 heavy chain
+分子 #9: PALMITIC ACID
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TECNAI F30 |
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撮影 | フィルム・検出器のモデル: FEI FALCON III (4k x 4k) 検出モード: INTEGRATING / 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 3.4 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | ![]() モデル: Tecnai F30 / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.03 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 81761 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |