SARS-CoV-2 nucleocapsid protein phase separates with G3BPs to disassemble stress granules and facilitate viral production  

新冠病毒N蛋白与G3BP发生相分离从而促进应激颗粒解组装和病毒产生

作　　者：Lingling Luo Zhean Li Tiejun Zhao Xiaohui Ju Peixiang Ma Boxing Jin Yulin Zhou Su He Jinhua Huang Xun Xu Yan Zou Ping Li Aibin Liang Jia Liu Tian Chi Xingxu Huang Qiang Ding Zhigang Jin Cheng Huang Yu Zhang 骆玲玲;李哲安;赵铁军;鞠晓辉;马培翔;金博星;周钰林;何素;黄金华;徐璕;邹晏;李萍;梁爱斌;刘佳;池天;黄行许;丁强;金志刚;黄诚;张玉(School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China;Shanghai Institute for Advanced Immunochemical Studies,ShanghaiTech University,Shanghai 201210,China;College of Chemistry and Life Sciences,Zhejiang Normal University,Jinhua 321004,China;Center for Infectious Disease Research.School of Medicine,Tsinghua University,Beijing 100084,China;Department of Hematology,Tongji Hospital of Tongji University,Shanghai 200065,China;Beijing Advanced Innovation Center for Structural Biology,Tsinghua University,Beijing 100084,China)

机构地区：[1]School of Phannacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [2]School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China [3]Shanghai Institute for Advanced Immunochemical Studies,ShanghaiTech University,Shanghai 201210,China [4]College of Chemistry and Life Sciences,Zhejiang Normal University,Jinhua 321004,China [5]Center for Infectious Disease Research.School of Medicine,Tsinghua University,Beijing 100084,China [6]Department of Hematology,Tongji Hospital of Tongji University,Shanghai 200065,China [7]Beijing Advanced Innovation Center for Structural Biology,Tsinghua University,Beijing 100084,China

出　　处：《Science Bulletin》2021年第12期1194-1204,M0004,共12页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(81830004,31970755,and 31970173);the Local Grant(608285568031)。

摘　　要：A key to tackling the coronavirus disease 2019(COVID-19)pandemic is to understand how severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)manages to outsmart host antiviral defense mechanisms.Stress granules(SGs),which are assembled during viral infection and function to sequester host and viral m RNAs and proteins,are part of the antiviral responses.Here,we show that the SARS-Co V-2 nucleocapsid(N)protein,an RNA binding protein essential for viral production,interacted with RasGTPase-activating protein SH3-domain-binding protein(G3 BP)and disrupted SG assembly,both of which require intrinsically disordered region1(IDR1)in N protein.The N protein partitioned into SGs through liquid-liquid phase separation with G3 BP,and blocked the interaction of G3 BP1 with other SG-related proteins.Moreover,the N protein domains important for phase separation with G3 BP and SG disassembly were required for SARS-Co V-2 viral production.We propose that N protein-mediated SG disassembly is crucial for SARS-Co V-2 production.新型冠状病毒SARS-CoV-2的爆发导致全世界数以百万计人员的感染和死亡,有效的治疗和干预措施对疫情的控制至关重要.然而到目前为止,新冠病毒逃过宿主抗病毒反应的机制尚未明确.病毒感染宿主细胞时,宿主能够迅速启动细胞的压力应答机制,终止细胞内的蛋白翻译,形成应激颗粒.本研究发现新型冠状病毒核衣壳蛋白(N蛋白)—一种在病毒组装过程非常关键的RNA结合蛋白,与宿主的G3BP蛋白(应激颗粒组装过程中关键的RNA结合蛋白)相互作用,并促进应激颗粒的解组装.N蛋白通过与G3BP发生相分离从而渗入应激颗粒中,阻断了G3BP与其他应激颗粒内蛋白的相互作用,最终破坏了应激颗粒的组装.这一N蛋白介导的相分离过程最终会促进病毒逃过宿主的抗病毒反应,从而有利于病毒的产生.

关 键 词：SARS-CoV-2 Nucleocapsid protein Stress granules Liquid-liquid phase separation G3BP Viral production 

分 类 号：R373[医药卫生—病原生物学]