Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating.
Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating.
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冷冻电镜结构揭示了受体引发的柯萨奇病毒脱壳的分子基础
DOI：
10.1016/j.chom.2021.01.001
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发表时间：
2021-03-10
影响因子：
30.3
通讯作者：
Xia N
中科院分区：
文献类型：
--
作者：
Xu L;Zheng Q;Zhu R;Yin Z;Yu H;Lin Y;Wu Y;He M;Huang Y;Jiang Y;Sun H;Zha Z;Yang H;Huang Q;Zhang D;Chen Z;Ye X;Han J;Yang L;Liu C;Que Y;Fang M;Gu Y;Zhang J;Luo W;Zhou ZH;Li S;Cheng T;Xia N
肠病毒剥膜受体结合在围绕每个衣壳顶点的表面凹陷处（“峡谷”），导致宿主衍生的脂质释放，称为“口袋因子”，该因子被埋在由主要病毒衣壳蛋白VP1形成的疏水口袋中。柯萨奇病毒和腺病毒受体（CAR）是B族柯萨奇病毒（CVB）的通用剥膜受体。在这里，我们展示了5个高分辨率的CVB冷冻电镜结构，代表了病毒感染的不同阶段。结构比较表明，CAR比其他未覆盖的受体更深入峡谷，导致一系列事件：与低pH相比，在中性pH下VP1疏水性口袋的崩溃，口袋因子的高效释放，病毒的脱壳和基因组释放。此外，我们发现了一种有效的治疗性抗体，它可以通过干扰病毒粒子- car相互作用，破坏衣壳的稳定和诱导病毒粒子的破坏来中和病毒感染。总之，这些结果确定了CVB细胞进入和抗体中和的结构基础。Xu等人展示了在生理条件下由受体CAR介导的B族柯萨奇病毒（CVB）脱衣的分子机制。通过car引导策略，他们鉴定出一种单克隆抗体，该抗体可以破坏衣壳的稳定性，破坏病毒粒子，并在体内有效地中和CVB感染。
Enterovirus uncoating receptors bind at the surface depression (“canyon”) that encircles each capsid vertex causing the release of a host-derived lipid called “pocket factor” that is buried in a hydrophobic pocket formed by the major viral capsid protein, VP1. Coxsackievirus and adenovirus receptor (CAR) is a universal uncoating receptor of group B coxsackieviruses (CVB). Here, we present five high-resolution cryoEM structures of CVB representing different stages of virus infection. Structural comparisons show that the CAR penetrates deeper into the canyon than other uncoating receptors, leading to a cascade of events: collapse of the VP1 hydrophobic pocket, high-efficiency release of the pocket factor and viral uncoating and genome release under neutral pH, as compared with low pH. Furthermore, we identified a potent therapeutic antibody that can neutralize viral infection by interfering with virion-CAR interactions, destabilizing the capsid and inducing virion disruption. Together, these results define the structural basis of CVB cell entry and antibody neutralization. Xu et al. present cryoEM structures that decipher the molecular mechanism of group B coxsackievirus (CVB) uncoating mediated by its receptor, CAR, under physiological conditions. Through a CAR-guided strategy, they identify a monoclonal antibody that can destabilize the capsid, disrupt the virion, and potently neutralize CVB infection in vivo.
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影响因子：
4.1
作者：
Hodik M;Anagandula M;Fuxe J;Krogvold L;Dahl-Jørgensen K;Hyöty H;Sarmiento L;Frisk G;POD-V Consortium
通讯作者：
POD-V Consortium
影响因子：
5.4
作者：
FRICKS, CE;HOGLE, JM
通讯作者：
HOGLE, JM
影响因子：
3.4
作者：
Delogu, Roberto;Battistone, Andrea;Stefanelli, Paola
通讯作者：
Stefanelli, Paola
影响因子：
33.9
作者：
Abedi, Glen R.;Watson, John T.;Gerber, Susan I.
通讯作者：
Gerber, Susan I.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH