Structure and uncoating of immature adenovirus.
Structure and uncoating of immature adenovirus.
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DOI：
10.1016/j.jmb.2009.06.057
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发表时间：
2009-09-18
影响因子：
5.6
通讯作者：
San Martin, Carmen
中科院分区：
文献类型：
--
作者：
Perez-Berna, Ana J.;Marabini, Roberto;Scheres, Sjors H. W.;Menendez-Conejero, Rosa;Dmitriev, Igor P.;Curiel, David T.;Mangel, Walter F.;Flint, S. Jane;San Martin, Carmen
通过蛋白水解加工的成熟是病毒世界中的常见特征，并且通常伴随着衣壳中的大的构象变化和重排。已显示腺病毒蛋白酶在病毒感染周期中发挥双重作用：（a）在成熟中，因为病毒装配以几种结构蛋白的前体开始，但以成熟病毒粒子中的蛋白水解加工形式结束;以及（B）在进入中，因为蛋白酶受损的病毒难以内体逃逸和脱壳。事实上，没有经过蛋白水解过程的病毒是没有传染性的。我们提出了不成熟的腺病毒颗粒的三维结构，所代表的温度敏感的突变体Ad 2 ts 1在非允许条件下生长，并将其与成熟的衣壳。我们的亚纳米分辨率的3DEM图表明，腺病毒成熟不涉及大规模的衣壳构象变化。差异图揭示了未加工的肽pIIIa和pVI的位置，并有助于确定它们在衣壳组装和成熟中的作用。一个有趣的差异出现在核心，表明一个更紧凑的组织和不成熟的核心的稳定性增加。我们进一步研究了这些特性，在体外拆卸试验。荧光和电子显微镜实验揭示了不成熟病毒在衣壳和核心水平上的稳定性和脱壳的差异，以及先前未成像的拆解中间体。
Maturation via proteolytical processing is a common trait in the viral world, and is often accompanied by large conformational changes and rearrangements in the capsid. The adenovirus protease has been shown to play a dual role in the viral infectious cycle: (a) in maturation, as viral assembly starts with precursors to several of the structural proteins, but ends with proteolytically processed versions in the mature virion; and (b) in entry, because protease-impaired viruses have difficulties in endosome escape and uncoating. Indeed, viruses that have not undergone proteolytical processing are not infectious. We present the 3D structure of immature adenovirus particles, as represented by the thermosensitive mutant Ad2 ts1 grown under non-permissive conditions, and compare it with the mature capsid. Our 3DEM maps at subnanometer resolution indicate that adenovirus maturation does not involve large scale conformational changes in the capsid. Difference maps reveal the location of unprocessed peptides pIIIa and pVI and help to define their role in capsid assembly and maturation. An intriguing difference appears in the core, indicating a more compact organization and increased stability of the immature cores. We have further investigated these properties by in vitro disassembly assays. Fluorescence and electron microscopy experiments reveal differences in the stability and uncoating of immature viruses, both at the capsid and core levels, as well as disassembly intermediates not previously imaged.
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影响因子：
11.4
作者：
Fabry, CMS;Rosa-Calatrava, M;Schoehn, G
通讯作者：
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Deléage, G
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