EMD-30805
Cryo-EM structure of Coxsackievirus B1 mature virion
EMD-30805
Single-particle3.2 Å
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Map released: 05/05/2021
Last modified: 27/03/2024
Sample Organism:
Coxsackievirus B1
Sample: Coxsackievirus B1
Fitted models: 7dpf (Avg. Q-score: 0.601)
Deposition Authors: Zheng Q, Li S
Sample: Coxsackievirus B1
Fitted models: 7dpf (Avg. Q-score: 0.601)
Deposition Authors: Zheng Q, Li S
Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating.
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
(2021) Cell Host Microbe , 29 , 448 - 462.e5
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(2021) Cell Host Microbe , 29 , 448 - 462.e5
Abstract:
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.
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.