Structural basis and function of the N terminus of SARS-CoV-2 nonstructural protein 1

• Main Authors: Zhao, Kaitao, Ke, Zunhui, Hu, Hongbing, Liu, Yahui, Li, Aixin, Hua, Rong, Guo, Fangteng, Xiao, Junfeng, Zhang, Yu, Duan, Ling, Yan, Xin-Fu, Gao, Yong-Gui, Liu, Bing, Xia, Yuchen, Li, Yan
• 其他作者: School of Biological Sciences
• 格式: Article
• 語言: English
• 出版: 2022
• 主題: Science::Biological sciences; N Terminus; SARS-CoV-2
• 在線閱讀: https://hdl.handle.net/10356/154058
• 機構: Nanyang Technological University

Nonstructural protein 1 (Nsp1) of severe acute respiratory syndrome coronaviruses (SARS-CoVs) is an important pathogenic factor that inhibits host protein translation by means of its C terminus. However, its N-terminal function remains elusive. Here, we determined the crystal structure of the N terminus (amino acids [aa] 11 to 125) of SARS-CoV-2 Nsp1 at a 1.25-Å resolution. Further functional assays showed that the N terminus of SARS-CoVs Nsp1 alone loses the ability to colocalize with ribosomes and inhibit protein translation. The C terminus of Nsp1 can colocalize with ribosomes, but its protein translation inhibition ability is significantly weakened. Interestingly, fusing the C terminus of Nsp1 with enhanced green fluorescent protein (EGFP) or other proteins in place of its N terminus restored the protein translation inhibitory ability to a level equivalent to that of full-length Nsp1. Thus, our results suggest that the N terminus of Nsp1 is able to stabilize the binding of the Nsp1 C terminus to ribosomes and act as a nonspecific barrier to block the mRNA channel, thus abrogating host mRNA translation.