Open AccessStructural Basis and Function of the N Terminus of SARS-CoV-2 Nonstructural Protein 1
Author(s) -
Kaitao Zhao,
Zunhui Ke,
Hsiao Yun Hu,
Yahui Liu,
Aixin Li,
Rong Hua,
Fangteng Guo,
Junfeng Xiao,
Zhang Yu,
Luchun Duan,
Xin-Fu Yan,
YongGui Gao,
Bing Liu,
Yuchen Xia,
Yan Li
Publication year - 2021
Publication title -
microbiology spectrum
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.502
H-Index - 51
ISSN - 2165-0497
DOI - 10.1128/spectrum.00169-21
Subject(s) - n terminus , function (biology) , covid-19 , coronavirus , translation (biology) , c terminus , structural protein , biology , virology , peptide sequence , gene , microbiology and biotechnology , genetics , virus , medicine , amino acid , messenger rna , disease , infectious disease (medical specialty)
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.