Zhang Changhui, Chen Yiping, Li Li, Yang Yan, He Jun, Chen Cheng, Su Dan
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041 PR China.
CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530 PR China.
Mol Biomed. 2020;1(1):5. doi: 10.1186/s43556-020-00005-0. Epub 2020 Aug 20.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of a potentially fatal disease named coronavirus disease 2019 (COVID-19), has raised significant public health concerns globally. To date, the COVID-19 pandemic has caused millions of people to be infected with SARS-CoV-2 worldwide. It has been known since the 2003 SARS epidemic that coronaviruses (CoVs) have large RNA genomes, the replication of which requires an RNA-dependent RNA replication/transcription complex. CoV nonstructural proteins (Nsps) play pivotal roles in the assembly of this complex and associated enzymatic functions in virus genomic replication. Several smaller nonenzymatic Nsps assist with RNA-dependent RNA polymerase function. In this study, we determined the structure of SARS-CoV-2 nonstructural protein 9 (nsp9), an RNA-binding protein that is essential for CoV replication. Its homotetrameric structure with two stable dimeric interfaces provids a structural basis for understanding the mechanisms of RNA-binding protein self-assembly, which may be essential for the regulation of viral RNA replication and transcription.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是一种名为2019冠状病毒病（COVID-19）的潜在致命疾病的病原体，在全球引起了重大的公共卫生关注。迄今为止，COVID-19大流行已导致全球数百万人感染SARS-CoV-2。自2003年SARS疫情以来，人们就知道冠状病毒（CoV）具有庞大的RNA基因组，其复制需要依赖RNA的RNA复制/转录复合体。CoV非结构蛋白（Nsps）在该复合体的组装以及病毒基因组复制中的相关酶功能中起关键作用。一些较小的非酶Nsps协助依赖RNA的RNA聚合酶功能。在本研究中，我们确定了SARS-CoV-2非结构蛋白9（nsp9）的结构，nsp9是一种对CoV复制至关重要的RNA结合蛋白。其具有两个稳定二聚体界面的同四聚体结构为理解RNA结合蛋白自组装机制提供了结构基础，这可能对病毒RNA复制和转录的调控至关重要。
