Abstract The molecular mechanisms that drive the infection by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)—the causative agent of coronavirus disease 2019 (COVID‐19)—are under intense current scrutiny to understand how the virus operates and to uncover ways in which the disease can be prevented or alleviated. Recent proteomic screens of the interactions between viral and host proteins have identified the human proteins targeted by SARS‐CoV‐2. The DNA polymerase α (Pol α)–primase complex or primosome—responsible for initiating DNA synthesis during genomic duplication—was identified as a target of nonstructural protein 1 (nsp1), a major virulence factor in the SARS‐CoV‐2 infection. Here, we validate the published reports of the interaction of nsp1 with the primosome by demonstrating direct binding with purified recombinant components and providing a biochemical characterization of their interaction. Furthermore, we provide a structural basis for the interaction by elucidating the cryo‐electron microscopy structure of nsp1 bound to the primosome. Our findings provide biochemical evidence for the reported targeting of Pol α by the virulence factor nsp1 and suggest that SARS‐CoV‐2 interferes with Pol α’s putative role in the immune response during the viral infection. PDB Code(s): 7OPL ; EMDB codes: 13020 , 13021
【저자키워드】 SARS‐CoV‐2, cryo‐EM, DNA polymerase α–primase, nsp1, protein–protein interaction, 【초록키워드】 coronavirus disease, viral infection, Coronavirus disease 2019, coronavirus, immune response, Infection, molecular mechanism, severe acute respiratory syndrome Coronavirus, virus, SARS‐CoV‐2, DNA, Viral, Microscopy, nsp1, target, respiratory, virulence, genomic, proteomic, binding, Interaction, nonstructural protein 1, causative agent, virulence factor, acute respiratory syndrome, biochemical, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, complex, human proteins, molecular mechanisms, host protein, biochemical evidence, SARS‐CoV‐2 infection, component, scrutiny, DNA polymerase, PDB, recent, reported, the disease, interfere, prevented, purified, human protein, 【제목키워드】 DNA, virulence, Interaction, polymerase,