近日，
研究人员报道了α-病毒基孔肯雅病毒的非结构蛋白1（nsP1）冷冻电镜结构，该结构负责RNA加帽和病毒复制机器的膜结合。该结构显示了其活性形式，并组装在单位膜相关的十二聚体环中。
该结构揭示了加帽酶的膜结合、寡聚和变构活化之间偶联的结构基础。化学计量法将病毒复制复合物重新定义为RNA合成反应器。该复合物的环状形貌意味着它在控制病毒细胞器进入以及确保加帽病毒RNA的退出方面具有作用。这些结果提供了有关正义单链RNA病毒复制机器膜结合的高分辨率信息，并为进一步表征细胞膜上的病毒复制和生产抗病毒剂开辟了道路。
据了解，正向单链RNA病毒，例如冠状病毒、黄病毒和α病毒，在宿主细胞内的病毒诱导的膜细胞器内进行转录和复制。用于形成这些细胞器的宿主细胞膜的重塑与病毒复制复合物的膜缔合和RNA合成相关。这些病毒壁可以浓缩代谢产物和蛋白质，从而合成病毒RNA，并阻止细胞先天免疫系统对该RNA的检测。
附：英文原文
Title: Capping pores of alphavirus nsP1 gate membranous viral replication factories
Author: Rhian Jones, Gabriel Bragagnolo, Roco Arranz, Juan Reguera
Issue&Volume: 2020-12-16
Abstract: Positive-sense single-stranded RNA viruses, such as coronaviruses, flaviviruses and alphaviruses, carry out transcription and replication inside virus-induced membranous organelles within host cells1,2,3,4,5,6,7. The remodelling of the host-cell membranes for the formation of these organelles is coupled to the membrane association of viral replication complexes and to RNA synthesis. These viral niches allow for the concentration of metabolites and proteins for the synthesis of viral RNA, and prevent the detection of this RNA by the cellular innate immune system8. Here we present the cryo-electron microscopy structure of non-structural protein 1 (nsP1) of the alphavirus chikungunya virus, which is responsible for RNA capping and membrane binding of the viral replication machinery. The structure shows the enzyme in its active form, assembled in a monotopic membrane-associated dodecameric ring. The structure reveals the structural basis of the coupling between membrane binding, oligomerization and allosteric activation of the capping enzyme. The stoichiometry—with 12 active sites in a single complex—redefines viral replication complexes as RNA synthesis reactors. The ring shape of the complex implies it has a role in controlling access to the viral organelle and ensuring the exit of properly capped viral RNA. Our results provide high-resolution information about the membrane association of the replication machinery of positive-sense single-stranded RNA viruses, and open up avenues for the further characterization of viral replication on cell membranes and the generation of antiviral agents.
DOI: 10.1038/s41586-020-3036-8
Source: https://www.nature.com/articles/s41586-020-3036-8
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
