Bunyamwera virus possesses a distinct nucleocapsid protein to facilitate genome encapsidation
Bunyamwera virus possesses a distinct nucleocapsid protein to facilitate genome encapsidation
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布尼亚姆维拉病毒具有独特的核衣壳蛋白，可促进基因组衣壳化
DOI：
10.1073/pnas.1222552110
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发表时间：
2013-05-28
影响因子：
11.1
通讯作者：
Lou, Zhiyong
中科院分区：
文献类型：
--
作者：
Li, Baobin;Wang, Quan;Lou, Zhiyong
布尼亚韦拉病毒（Bunyamwera virus，BUNV）是布尼亚病毒科（Bunyaviridae）的典型病毒，属于正布尼亚病毒属（Orthobunyavirus）。与其他负义单链RNA病毒类似，布尼亚病毒具有核衣壳蛋白（NP）以促进基因组RNA的折叠和病毒复制。布尼亚病毒科不同属成员的两个核蛋白的结构已被报道。然而，它们的结构、RNA结合特征和RNA结合以外的功能彼此显著不同。在这里，我们报告的晶体结构的BUNV NP-RNA复合物。发现BUNV NP的多肽在病毒NP中具有不同的折叠。一个N-末端臂和一个C-末端尾被发现与相邻的NP原聚体相互作用，形成一个四聚体的环状组织。每个原聚体在N叶和C叶之间的正电荷缝隙中结合从表达宿主获得的10-nt RNA分子。观察到重组BUNV NP-RNA复合物的不均匀寡聚化，其类似于裂谷热病毒NP-RNA复合物。这一结果表明，一个NP原体与相邻原体的灵活性的基础BUNV核糖核蛋白复合物（RNP）的形成。电子显微镜显示，单体大小的NP-RNA复合物的天然BUNV RNP的积木。结合以前的结果表明，诱变的interprotomer或蛋白质-RNA接口影响BUNV复制，我们的结构提供了一个很大的潜力，了解负义单链RNA RNP形成的机制，并使针对BUNV RNP形成的抗病毒治疗的发展。
Bunyamwera virus (BUNV), which belongs to the genus Orthobunyavirus, is the prototypical virus of the Bunyaviridae family. Similar to other negative-sense single-stranded RNA viruses, bunyaviruses possess a nucleocapsid protein (NP) to facilitate genomic RNA encapsidation and virus replication. The structures of two NPs of members of different genera within the Bunyaviridae family have been reported. However, their structures, RNA-binding features, and functions beyond RNA binding significantly differ from one another. Here, we report the crystal structure of the BUNV NP-RNA complex. The polypeptide of the BUNV NP was found to possess a distinct fold among viral NPs. An N-terminal arm and a C-terminal tail were found to interact with neighboring NP protomers to form a tetrameric ring-shaped organization. Each protomer bound a 10-nt RNA molecule, which was acquired from the expression host, in the positively charged crevice between the N and C lobes. Inhomogeneous oligomerization was observed for the recombinant BUNV NP-RNA complex, which was similar to the Rift Valley fever virus NP-RNA complex. This result suggested that the flexibility of one NP protomer with adjacent protomers underlies the BUNV ribonucleoprotein complex (RNP) formation. Electron microscopy revealed that the monomer-sized NP-RNA complex was the building block of the natural BUNV RNP. Combined with previous results indicating that mutagenesis of the interprotomer or protein-RNA interface affects BUNV replication, our structure provides a great potential for understanding the mechanism underlying negative-sense single-stranded RNA RNP formation and enables the development of antiviral therapies targeting BUNV RNP formation.