Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
Department of Biology, University of York, York, YO10 5DD, UK.
Sci Rep. 2024 Jun 18;14(1):14099. doi: 10.1038/s41598-024-58243-z.
We report the first cryoEM structure of the Hendra henipavirus nucleoprotein in complex with RNA, at 3.5 Å resolution, derived from single particle analysis of a double homotetradecameric RNA-bound N protein ring assembly exhibiting D14 symmetry. The structure of the HeV N protein adopts the common bi-lobed paramyxoviral N protein fold; the N-terminal and C-terminal globular domains are bisected by an RNA binding cleft containing six RNA nucleotides and are flanked by the N-terminal and C-terminal arms, respectively. In common with other paramyxoviral nucleocapsids, the lateral interface between adjacent N and N protomers involves electrostatic and hydrophobic interactions mediated primarily through the N-terminal arm and globular domains with minor contribution from the C-terminal arm. However, the HeV N multimeric assembly uniquely identifies an additional protomer-protomer contact between the N N-terminus and N C-terminal arm linker. The model presented here broadens the understanding of RNA-bound paramyxoviral nucleocapsid architectures and provides a platform for further insight into the molecular biology of HeV, as well as the development of antiviral interventions.
我们报告了亨德拉尼帕病毒核蛋白与 RNA 复合物的首个冷冻电镜结构，分辨率为 3.5Å，源自双同源十四聚体 RNA 结合 N 蛋白环组装的单颗粒分析，该组装显示 D14 对称性。HeV N 蛋白的结构采用常见的双叶状副粘病毒 N 蛋白折叠；N 端和 C 端球状结构域被包含六个 RNA 核苷酸的 RNA 结合裂隙平分，分别由 N 端臂和 C 端臂侧翼。与其他副粘病毒核衣壳一样，相邻 N 和 N 原聚体之间的侧界面涉及静电和疏水相互作用，主要通过 N 端臂和球状结构域介导，C 端臂的贡献较小。然而，HeV N 多聚体组装独特地确定了 N N 末端和 N C 末端臂接头之间的另一个原聚体-原聚体接触。这里提出的模型拓宽了对 RNA 结合副粘病毒核衣壳结构的理解，并为进一步了解 HeV 的分子生物学以及抗病毒干预措施的发展提供了一个平台。
