Structure and assembly of the Ebola virus nucleocapsid.

Structure and assembly of the Ebola virus nucleocapsid.
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DOI:
10.1038/nature24490
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发表时间:
2017-11-16
期刊:
影响因子:
64.8
通讯作者:
Briggs JAG
Briggs JAG
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wan W;Kolesnikova L;Clarke M;Koehler A;Noda T;Becker S;Briggs JAG

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埃博拉病毒和马尔堡病毒都是丝状病毒:引起出血热的丝状包膜病毒。丝状病毒属于单负病毒目,其还包括狂犬病病毒、麻疹病毒和呼吸道合胞病毒。单负病毒具有非节段的单链负义RNA基因组,其被核蛋白(NP)和其他病毒蛋白包被以形成螺旋核衣壳(NC)。NC作为病毒组装的支架和作为基因组转录和复制的模板。NP-NP相互作用的见解来自于寡聚化的、RNA标记的NP的结构研究和NC或NC样结构的低温电子显微镜(cryo-EM)。目前还没有完整的单负病毒NC的高分辨率重建。在这里,我们应用冷冻电子断层扫描和subtomograms平均,以确定完整的病毒和重组NC样组件内的埃博拉病毒NC的结构。这些结构揭示了NC组分的身份和排列,并表明从NP核心的无序C-末端区域形成延伸的α-螺旋连接NP寡聚化、NC缩合、RNA聚合和辅助蛋白募集。
Ebola and Marburg viruses are filoviruses: filamentous, enveloped viruses that cause hemorrhagic fever. Filoviruses are within the order Mononegavirales which also includes rabies virus, measles virus, and respiratory syncytial virus. Mononegaviruses have non-segmented, single-stranded negative-sense RNA genomes that are encapsidated by nucleoprotein (NP) and other viral proteins to form a helical nucleocapsid (NC). NC acts as a scaffold for virus assembly and as a template for genome transcription and replication. Insights into NP-NP interactions have been derived from structural studies of oligomerized, RNA-encapsidating NP and cryo-electron microscopy (cryo-EM) of NC or NC-like structures. There have been no high-resolution reconstructions of complete mononegavirus NCs. Here, we have applied cryo-electron tomography and subtomogram averaging to determine the structure of Ebola virus NC within intact viruses and recombinant NC-like assemblies. These structures reveal the identity and arrangement of the NC components, and suggest that the formation of an extended alpha-helix from the disordered C-terminal region of NP-core links NP oligomerization, NC condensation, RNA encapsidation, and accessory protein recruitment.
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