Structures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus.
Structures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus.
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MHV-A59 Nucleocapsid蛋白的N-和C末端结构域的结构证实了冠状病毒中保守的RNA-蛋白结合机制。
DOI：
10.1007/s13238-010-0079-x
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发表时间：
2010-07
期刊：
影响因子：
21.1
通讯作者：
Rao Z
中科院分区：
文献类型：
--
作者：
Ma Y;Tong X;Xu X;Li X;Lou Z;Rao Z
冠状病毒是动物和人类呼吸道和肠道疾病的病原体。一个例子是SARS，它在2003年造成了全球性的健康威胁。在冠状病毒中，结构蛋白N（核衣壳蛋白）与病毒RNA结合形成丝状核衣壳，在基因组复制和转录中起着至关重要的作用。MHV N蛋白N端结构域的结构也表明其与转录调控序列（TRS）RNA的特异性结合。在这里，我们报告的两个蛋白水解耐N-（NTD）和C-末端（CTD）结构域的N蛋白从小鼠肝炎病毒（MHV）的晶体结构。将两种不同晶型的NTD的结构解析至1.5 μ m。高分辨率提供了比以前报道更详细的结构信息，表明MHV的NTD结构与SARS-CoV和IBV的NTD结构具有相似的整体和拓扑结构，但其潜在表面不同，这表明RNA结合模块可能存在差异。CTD的结构解析至2.0-μ m分辨率，并显示出紧密缠绕的二聚体。这与分析超离心实验一致，表明N蛋白的二聚体组装。SARS冠状病毒、IBV和MHV的这两个结构域的结构相似性证实了冠状病毒核衣壳形成的保守机制。
Coronaviruses are the causative agent of respiratory and enteric diseases in animals and humans. One example is SARS, which caused a worldwide health threat in 2003. In coronaviruses, the structural protein N (nucleocapsid protein) associates with the viral RNA to form the filamentous nucleocapsid and plays a crucial role in genome replication and transcription. The structure of Nterminal domain of MHV N protein also implicated its specific affinity with transcriptional regulatory sequence (TRS) RNA. Here we report the crystal structures of the two proteolytically resistant N- (NTD) and C-terminal (CTD) domains of the N protein from murine hepatitis virus (MHV). The structure of NTD in two different crystal forms was solved to 1.5 Å. The higher resolution provides more detailed structural information than previous reports, showing that the NTD structure from MHV shares a similar overall and topology structure with that of SARS-CoV and IBV, but varies in its potential surface, which indicates a possible difference in RNA-binding module. The structure of CTD was solved to 2.0-Å resolution and revealed a tightly intertwined dimer. This is consistent with analytical ultracentrifugation experiments, suggesting a dimeric assembly of the N protein. The similarity between the structures of these two domains from SARS-CoV, IBV and MHV corroborates a conserved mechanism of nucleocapsid formation for coronaviruses.