A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71

被引：350

作者：

Wang, Xiangxi ^{[2
]}

Peng, Wei ^{[2
]}

Ren, Jingshan ^{[1
]}

Hu, Zhongyu ^{[3
]}

Xu, Jiwei ^{[2
]}

Lou, Zhiyong ^{[4
]}

Li, Xumei ^{[2
]}

Yin, Weidong ^{[3
]}

Shen, Xinliang ^{[3
]}

Porta, Claudine ^{[1
]}

Walter, Thomas S. ^{[1
]}

Evans, Gwyndaf ^{[5
]}

Axford, Danny ^{[5
]}

Owens, Robin ^{[5
]}

Rowlands, David J. ^{[6
,7
]}

Wang, Junzhi ^{[3
]}

Stuart, David I. ^{[1
,5
]}

Fry, Elizabeth E. ^{[1
]}

Rao, Zihe ^{[2
,4
]}

机构：

[1] Univ Oxford, Div Struct Biol, Oxford, England

[2] Chinese Acad Sci, Inst Biophys, Natl Lab Macromol, Beijing 100080, Peoples R China

[3] Natl Inst Food & Drug Control, Beijing, Peoples R China

[4] Tsinghua Univ, Sch Med, Struct Biol Lab, Beijing 100084, Peoples R China

[5] Diamond Light Sources, Didcot, Oxon, England

[6] Univ Leeds, Inst Mol & Cellular Biol, Fac Biol Sci, Leeds, W Yorkshire, England

[7] Univ Leeds, Astbury Ctr Struct Mol Biol, Fac Biol Sci, Leeds, W Yorkshire, England

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2012年 / 19卷 / 04期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

CRYSTAL-STRUCTURE; CELLULAR RECEPTOR; EXTERNALIZED POLYPEPTIDE; MATURATION CLEAVAGE; HUMAN RHINOVIRUS-14; CAPSID PROTEIN; POLIOVIRUS; VIRUS; IDENTIFICATION; RESOLUTION;

D O I：

10.1038/nsmb.2255

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：424 / 429

页数：6

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