Structural basis and function of the N terminus of SARS-CoV-2 nonstructural protein 1
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 term...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2022
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| Online Access: | https://hdl.handle.net/10356/154058 |
| _version_ | 1811685747033374720 |
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| author | 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 |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences 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 |
| author_sort | Zhao, Kaitao |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T04:49:26Z |
| format | Journal Article |
| id | ntu-10356/154058 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:49:26Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1540582023-02-28T17:10:01Z Structural basis and function of the N terminus of SARS-CoV-2 nonstructural protein 1 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 School of Biological Sciences Science::Biological sciences N Terminus SARS-CoV-2 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. Published version This work was supported by the National Natural Science Foundation of China (project no. 81971936 and 82041004), the Fundamental Research Funds for the Central Universities, Hubei Province’s Outstanding Medical Academic Leader program, Foundation for Innovative Research Groups of the National Natural Science Foundation of Hubei (project no. 2020CFA015), Foundation for Innovative Research Groups of Hubei Health Commission (project no. WJ2021C002), Huazhong University of Science and Technology (HUST) COVID-19 Rapid Response Call (2020kfyXGYJ036), and Wuhan Municipal Health Commission Emergency Fund for COVID-19 (EX20E04). 2022-02-15T02:38:16Z 2022-02-15T02:38:16Z 2021 Journal Article Zhao, K., Ke, Z., Hu, H., Liu, Y., Li, A., Hua, R., Guo, F., Xiao, J., Zhang, Y., Duan, L., Yan, X., Gao, Y., Liu, B., Xia, Y. & Li, Y. (2021). Structural basis and function of the N terminus of SARS-CoV-2 nonstructural protein 1. Microbiology Spectrum, 9(1), e00169-21-. https://dx.doi.org/10.1128/Spectrum.00169-21 2165-0497 https://hdl.handle.net/10356/154058 10.1128/Spectrum.00169-21 34132580 2-s2.0-85115904965 1 9 e00169-21 en Microbiology Spectrum © 2021 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. application/pdf |
| spellingShingle | Science::Biological sciences N Terminus SARS-CoV-2 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 Structural basis and function of the N terminus of SARS-CoV-2 nonstructural protein 1 |
| title | Structural basis and function of the N terminus of SARS-CoV-2 nonstructural protein 1 |
| title_full | Structural basis and function of the N terminus of SARS-CoV-2 nonstructural protein 1 |
| title_fullStr | Structural basis and function of the N terminus of SARS-CoV-2 nonstructural protein 1 |
| title_full_unstemmed | Structural basis and function of the N terminus of SARS-CoV-2 nonstructural protein 1 |
| title_short | Structural basis and function of the N terminus of SARS-CoV-2 nonstructural protein 1 |
| title_sort | structural basis and function of the n terminus of sars cov 2 nonstructural protein 1 |
| topic | Science::Biological sciences N Terminus SARS-CoV-2 |
| url | https://hdl.handle.net/10356/154058 |
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