title: A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71.
abstract: Enterovirus 71 (EV71) is a major agent of hand, foot and mouth disease in children that can cause severe central nervous system disease and death. No vaccine or antiviral therapy is available. High-resolution structural analysis of the mature virus and natural empty particles shows that the mature virus is structurally similar to other enteroviruses. In contrast, the empty particles are markedly expanded and resemble elusive enterovirus-uncoating intermediates not previously characterized in atomic detail. Hydrophobic pockets in the EV71 capsid are collapsed in this expanded particle, providing a detailed explanation of the mechanism for receptor-binding triggered virus uncoating. These structures provide a model for enterovirus uncoating in which the VP1 GH loop acts as an adaptor-sensor for cellular receptor attachment, converting heterologous inputs to a generic uncoating mechanism, highlighting new opportunities for therapeutic intervention.
authors.affiliation: National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China.
authors.forename: Xiangxi
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.forename: Jingshan
authors.initials: J
authors.lastname: Ren
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Hu
authors.forename: Jiwei
authors.initials: J
authors.lastname: Xu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lou
authors.forename: Xumei
authors.initials: X
authors.lastname: Li
authors.forename: Weidong
authors.initials: W
authors.lastname: Yin
authors.forename: Xinliang
authors.initials: X
authors.lastname: Shen
authors.forename: Claudine
authors.initials: C
authors.lastname: Porta
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Walter
authors.forename: Gwyndaf
authors.initials: G
authors.lastname: Evans
authors.forename: Danny
authors.initials: D
authors.lastname: Axford
authors.forename: Robin
authors.initials: R
authors.lastname: Owen
authors.forename: David J
authors.initials: DJ
authors.lastname: Rowlands
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
authors.forename: David I
authors.initials: DI
authors.lastname: Stuart
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Fry
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D002213:Capsid / Q000737:chemistry; D036022:Capsid Proteins / Q000737:chemistry; D018360:Crystallography, X-Ray; D029821:Enterovirus A, Human / Q000737:chemistry*; D004769:Enterovirus Infections / Q000821:virology*; D006232:Hand, Foot and Mouth Disease / Q000821:virology; D006801:Humans; D008958:Models, Molecular; D014771:Virion / Q000737:chemistry*
chemical_list: D036022:Capsid Proteins