Acquired Functional Capsid Structures in Metazoan Totivirus-like dsRNA Virus
Acquired Functional Capsid Structures in Metazoan Totivirus-like dsRNA Virus
复制标题
后生动物 Totivirus 样 dsRNA 病毒中获得的功能性衣壳结构
DOI：
10.1016/j.str.2020.04.016
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发表时间：
2020
期刊：
影响因子：
5.7
通讯作者：
Miyazaki Naoyuki
中科院分区：
文献类型：
--
作者：
Okamoto Kenta;Ferreira Ricardo J.;Larsson Daniel S.D.;Maia Filipe R.N.C.;Isawa Haruhiko;Sawabe Kyoko;Murata Kazuyoshi;Hajdu Janos;Iwasaki Kenji;Kasson Peter M.;Miyazaki Naoyuki
非包膜二十面体双链RNA(DsRNA)病毒具有增殖所需的多功能衣壳。原生动物/真菌dsRNA病毒具有相对简单的衣壳结构，足以满足其生命周期中的细胞内阶段，而后生动物dsRNA病毒获得了额外的结构特征，以适应多细胞宿主中细胞外细胞间的传播。在这里，我们提出了第一个后生动物dsRNA类病毒的原子模型，其结构揭示了三个独特的结构特征：C-末端互锁臂、表面突出环和在5倍对称轴上的孔处受阻。这些特性是理解后生动物dsRNA病毒衣壳功能的关键，如颗粒的稳定性和形成、细胞进入和内源性的mRNA颗粒内转录。在对封闭孔道进行分子动力学模拟的基础上，我们提出了类病毒颗粒内转录的一种可能机制，即在孔道的开放和关闭状态之间动态切换(S)。
Non-enveloped icosahedral double-stranded RNA (dsRNA) viruses possess multifunctional capsids required for their proliferation. Whereas protozoan/fungal dsRNA viruses have a relatively simple capsid structure, which suffices for the intracellular phase in their life cycle, metazoan dsRNA viruses have acquired additional structural features as an adaptation for extracellular cell-to-cell transmission in multicellular hosts. Here, we present the first atomic model of a metazoan dsRNA totivirus-like virus and the structure reveals three unique structural traits: a C-terminal interlocking arm, surface projecting loops, and an obstruction at the pore on the 5-fold symmetry axis. These traits are keys to understanding the capsid functions of metazoan dsRNA viruses, such as particle stability and formation, cell entry, and endogenous intraparticle transcription of mRNA. On the basis of molecular dynamics simulations of the obstructed pore, we propose a possible mechanism of intraparticle transcription in totivirus-like viruses, which dynamically switches between open and closed states of the pore(s).