3.5Å 分辨率冷冻电镜结构揭示甲病毒的宿主细胞进入和组装的意义。
Implication for alphavirus host-cell entry and assembly indicated by a 3.5Å resolution cryo-EM structure.
机构信息
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, People's Republic of China.
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 150069, Harbin, People's Republic of China.
出版信息
Nat Commun. 2018 Dec 14;9(1):5326. doi: 10.1038/s41467-018-07704-x.
Alphaviruses are enveloped RNA viruses that contain several human pathogens. Due to intrinsic heterogeneity of alphavirus particles, a high resolution structure of the virion is currently lacking. Here we provide a 3.5 Å cryo-EM structure of Sindbis virus, using block based reconstruction method that overcomes the heterogeneity problem. Our structural analysis identifies a number of conserved residues that play pivotal roles in the virus life cycle. We identify a hydrophobic pocket in the subdomain D of E2 protein that is stabilized by an unknown pocket factor near the viral membrane. Residues in the pocket are conserved in different alphaviruses. The pocket strengthens the interactions of the E1/E2 heterodimer and may facilitate virus assembly. Our study provides structural insights into alphaviruses that may inform the design of drugs and vaccines.
甲病毒是一类有包膜的 RNA 病毒，包含几种人类病原体。由于甲病毒颗粒的固有异质性，目前缺乏病毒的高分辨率结构。在这里，我们使用基于块的重建方法提供了辛德毕斯病毒的 3.5Å 冷冻电镜结构，该方法克服了异质性问题。我们的结构分析确定了一些保守残基，这些残基在病毒生命周期中起着关键作用。我们在 E2 蛋白的亚结构域 D 中发现了一个疏水性口袋，该口袋由靠近病毒膜的未知口袋因子稳定。口袋中的残基在不同的甲病毒中是保守的。该口袋增强了 E1/E2 异二聚体的相互作用，可能有助于病毒组装。我们的研究为甲病毒提供了结构见解，可能为药物和疫苗的设计提供信息。
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