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结构病毒学。麻疹病毒核衣壳的近原子冷冻电镜结构。

Structural virology. Near-atomic cryo-EM structure of the helical measles virus nucleocapsid.

机构信息

CNRS, Unit for Virus Host-Cell Interactions, 38042 Grenoble, France. Université Grenoble Alpes, Unit for Virus Host-Cell Interactions, 38042 Grenoble, France.

Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69917 Heidelberg, Germany.

出版信息

Science. 2015 May 8;348(6235):704-7. doi: 10.1126/science.aaa5137. Epub 2015 Apr 16.

Abstract

Measles is a highly contagious human disease. We used cryo-electron microscopy and single particle-based helical image analysis to determine the structure of the helical nucleocapsid formed by the folded domain of the measles virus nucleoprotein encapsidating an RNA at a resolution of 4.3 angstroms. The resulting pseudoatomic model of the measles virus nucleocapsid offers important insights into the mechanism of the helical polymerization of nucleocapsids of negative-strand RNA viruses, in particular via the exchange subdomains of the nucleoprotein. The structure reveals the mode of the nucleoprotein-RNA interaction and explains why each nucleoprotein of measles virus binds six nucleotides, whereas the respiratory syncytial virus nucleoprotein binds seven. It provides a rational basis for further analysis of measles virus replication and transcription, and reveals potential targets for drug design.

摘要

麻疹是一种高度传染性的人类疾病。我们使用冷冻电子显微镜和基于单颗粒的螺旋图像分析来确定麻疹病毒核蛋白折叠结构域形成的螺旋核衣壳的结构,该核衣壳包裹着 RNA,分辨率为 4.3 埃。麻疹病毒核衣壳的这个伪原子模型提供了对负链 RNA 病毒核衣壳螺旋聚合机制的重要见解,特别是通过核蛋白的交换亚结构域。该结构揭示了核蛋白 - RNA 相互作用的模式,并解释了为什么麻疹病毒的每个核蛋白结合六个核苷酸,而呼吸道合胞病毒核蛋白结合七个核苷酸。它为进一步分析麻疹病毒的复制和转录提供了合理的基础,并揭示了药物设计的潜在靶点。

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