Cryo-EM structures of two bovine adenovirus type 3 intermediates

Cryo-EM structures of two bovine adenovirus type 3 intermediates
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两种牛腺病毒3型中间体的冷冻电镜结构

DOI:
10.1016/j.virol.2013.12.012
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发表时间:
2014-02-01
期刊:
影响因子:
3.7
通讯作者:
Zhu, Ping
Zhu, Ping
中科院分区:
医学3区
文献类型:
--
作者:
Cheng, Lingpeng;Huang, Xiaoxing;Zhu, Ping

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腺病毒(Ads)感染所有脊椎动物物种的宿主,并已被研究作为疫苗载体。在这里,我们报告近原子结构的两个牛广告3型(BAd 3)的中间体通过冷冻电子显微镜获得。两种中间结构之间的比较表明,差异局限于五重顶点区域,而它们的小平面结构是相同的。BAd 3的整体小面结构表现出与人Ads相似的结构;然而,BAd 3蛋白IX具有独特的构象。质谱和冷冻电子断层扫描分析表明,一个中间结构代表DNA双链化过程中的阶段,而另一个中间结构代表一个较晚的阶段。这些结果也表明,裂解的前体蛋白VI发生在DNA的双糖苷化过程中,而不是之后。总体而言,我们的研究结果提供了深入了解的Ad组装的机制,并允许在骨干水平上的第一个结构比较人类和非人类的广告。(C)2013 Elsevier Inc. All rights reserved.
Adenoviruses (Ads) infect hosts from all vertebrate species and have been investigated as vaccine vectors. We report here near-atomic structures of two bovine Ad type 3 (BAd3) intermediates obtained by cryo-electron microscopy. A comparison between the two intermediate structures reveals that the differences are localized in the fivefold vertex region, while their facet structures are identical. The overall facet structure of BAd3 exhibits a similar structure to human Ads; however, BAd3 protein IX has a unique conformation. Mass spectrometry and cryo-electron tomography analyses indicate that one intermediate structure represents the stage during DNA encapsidation, whilst the other intermediate structure represents a later stage. These results also suggest that cleavage of precursor protein VI occurs during, rather than after, the DNA encapsidation process. Overall, our results provide insights into the mechanism of Ad assembly, and allow the first structural comparison between human and nonhuman Ads at backbone level. (C) 2013 Elsevier Inc. All rights reserved.