Immature and mature human astrovirus: structure, conformational changes, and similarities to hepatitis E virus.

Immature and mature human astrovirus: structure, conformational changes, and similarities to hepatitis E virus.
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DOI:
10.1016/j.jmb.2012.06.029
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发表时间:
2012-10-05
影响因子:
5.6
通讯作者:
Yeager M
Yeager M
中科院分区:
生物学2区
文献类型:
--
作者:
Dryden KA;Tihova M;Nowotny N;Matsui SM;Mendez E;Yeager M

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人类星状病毒(HAstV)是引起胃肠炎的主要原因。HAstV由结构蛋白VP90组装而成,并经历一系列蛋白水解性切割。对VP70的裂解是从细胞释放未成熟颗粒所必需的,随后被胰酶裂解使其具有感染性。我们使用电子冷冻显微镜和二十面体图像分析来确定第一个实验获得的、未成熟的VP70病毒粒子和完全蛋白分解的、有感染性的病毒粒子的三维结构。这两个粒子都表现出T=3的二十面体对称性和几乎相同的实心衣壳,直径约为~350奥拉。球状尖状物从衣壳表面发出,产生的总直径约为440英寸。未成熟的颗粒显示90个二聚体尖峰,而成熟的衣壳只显示30个尖峰,位于二十面体2折轴上。60个五角形尖峰的丧失可能在病毒传染性中起着重要作用。此外,未成熟的HAstV与戊型肝炎病毒(HEV)样颗粒的结构惊人地相似,正如先前从星形病毒棘突结构域的晶体结构与HEV P-结构域的结构相似性预测的那样[董,J.,董,L.,Méndez,E.&Tao,Y.(2011)]。人类星状病毒衣壳尖峰的晶体结构。程序娜塔莉。阿卡德。SCI。美国108,12681-12686]。衣壳和二聚体棘突之间以及衣壳蛋白序列之间的相似性表明,这些病毒家族在系统发育上是相关的,可能具有共同的组装和激活机制。未成熟和成熟HAstV的►三维电子显微镜密度图。►成熟病毒粒子在蛋白水解性切割后仅显示90个尖峰中的30个。►未成熟病毒粒子与HEV非常相似。
Human astroviruses (HAstVs) are a major cause of gastroenteritis. HAstV assembles from the structural protein VP90 and undergoes a cascade of proteolytic cleavages. Cleavage to VP70 is required for release of immature particles from cells, and subsequent cleavage by trypsin confers infectivity. We used electron cryomicroscopy and icosahedral image analysis to determine the first experimentally derived, three-dimensional structures of an immature VP70 virion and a fully proteolyzed, infectious virion. Both particles display T = 3 icosahedral symmetry and nearly identical solid capsid shells with diameters of ~ 350 Å. Globular spikes emanate from the capsid surface, yielding an overall diameter of ~ 440 Å. While the immature particles display 90 dimeric spikes, the mature capsid only displays 30 spikes, located on the icosahedral 2-fold axes. Loss of the 60 peripentonal spikes likely plays an important role in viral infectivity. In addition, immature HAstV bears a striking resemblance to the structure of hepatitis E virus (HEV)-like particles, as previously predicted from structural similarity of the crystal structure of the astrovirus spike domain with the HEV P-domain [Dong, J., Dong, L., Méndez, E. & Tao, Y. (2011). Crystal structure of the human astrovirus capsid spike. Proc. Natl. Acad. Sci. USA108, 12681–12686]. Similarities between their capsid shells and dimeric spikes and between the sequences of their capsid proteins suggest that these viral families are phylogenetically related and may share common assembly and activation mechanisms. ► Three‐dimensional electron cryomicroscopy density maps of immature and mature HAstV. ► Mature virions only display 30 of 90 spikes after proteolytic cleavage. ► Immature virions are remarkably similar to HEV.
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影响因子: 3.8
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发表时间: 1989-11-01
影响因子: 5.4
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