Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4275-80. doi: 10.1073/pnas.1120453109. Epub 2012 Feb 27.
Ebola virus is a highly pathogenic filovirus causing severe hemorrhagic fever with high mortality rates. It assembles heterogenous, filamentous, enveloped virus particles containing a negative-sense, single-stranded RNA genome packaged within a helical nucleocapsid (NC). We have used cryo-electron microscopy and tomography to visualize Ebola virus particles, as well as Ebola virus-like particles, in three dimensions in a near-native state. The NC within the virion forms a left-handed helix with an inner nucleoprotein layer decorated with protruding arms composed of VP24 and VP35. A comparison with the closely related Marburg virus shows that the N-terminal region of nucleoprotein defines the inner diameter of the Ebola virus NC, whereas the RNA genome defines its length. Binding of the nucleoprotein to RNA can assemble a loosely coiled NC-like structure; the loose coil can be condensed by binding of the viral matrix protein VP40 to the C terminus of the nucleoprotein, and rigidified by binding of VP24 and VP35 to alternate copies of the nucleoprotein. Four proteins (NP, VP24, VP35, and VP40) are necessary and sufficient to mediate assembly of an NC with structure, symmetry, variability, and flexibility indistinguishable from that in Ebola virus particles released from infected cells. Together these data provide a structural and architectural description of Ebola virus and define the roles of viral proteins in its structure and assembly.
埃博拉病毒是一种高致病性丝状病毒,可引起严重的出血热,死亡率很高。它组装出异质的、丝状的、包膜病毒颗粒,其中包含一个负义的、单链 RNA 基因组,被包装在一个螺旋核衣壳(NC)内。我们已经使用冷冻电子显微镜和断层扫描技术,以近自然状态对埃博拉病毒颗粒以及埃博拉病毒样颗粒进行了三维可视化。病毒粒子内的 NC 形成一个左手螺旋,内部核蛋白层装饰有由 VP24 和 VP35 组成的突出臂。与密切相关的马尔堡病毒的比较表明,核蛋白的 N 端区域定义了埃博拉病毒 NC 的内直径,而 RNA 基因组定义了其长度。核蛋白与 RNA 的结合可以组装出一个松散卷曲的 NC 样结构;病毒基质蛋白 VP40 与核蛋白 C 端的结合可以使松散卷曲的结构浓缩,VP24 和 VP35 与核蛋白的交替拷贝的结合可以使结构刚性化。NP、VP24、VP35 和 VP40 这四种蛋白是介导具有结构、对称性、可变性和灵活性的 NC 组装所必需且充分的,与从感染细胞中释放的埃博拉病毒颗粒中的 NC 没有区别。这些数据共同提供了埃博拉病毒的结构和架构描述,并定义了病毒蛋白在其结构和组装中的作用。
Proc Natl Acad Sci U S A. 2012-2-27
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