6LP9

the protein of cat virus

6LP9 の概要

• エントリーDOI: 10.2210/pdb6lp9/pdb
• 分子名称: nsp1 protein (2 entities in total)
• 機能のキーワード: cat virus, viral protein
• 由来する生物種: Feline infectious peritonitis virus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 54041.66

構造登録者

Shen, Z.,Peng, G.Q. (登録日: 2020-01-09, 公開日: 2020-08-12, 最終更新日: 2023-11-29)

主引用文献

Shen, Z.,Yang, Y.,Yang, S.,Zhang, G.,Xiao, S.,Fu, Z.F.,Peng, G.
Structural and Biological Basis of Alphacoronavirus nsp1 Associated with Host Proliferation and Immune Evasion.
Viruses, 12:-, 2020

PubMed Abstract: Non-structural protein 1 (nsp1) is only characterized in alphacoronaviruses (α-CoVs) and betacoronaviruses (β-CoVs). There have been extensive researches on how the β-CoVs nsp1 regulates viral virulence by inhibiting host protein synthesis, but the regulatory mechanism of the α-CoVs nsp1 is still unclear. Here, we report the 2.1-Å full-length crystal structure of nsp1 in emerging porcine SADS-CoV and the 1.8-Å full-length crystal structure of nsp1 in the highly lethal cat FIPV. Although they belong to different subtypes of α-CoVs, these viruses all have a bucket-shaped fold composed of six β-sheets, similar to the crystal structure of PEDV and TGEV nsp1. Comparing the above four structures, we found that the structure of α-CoVs nsp1 in the same subtype was more conserved. We then selected mammalian cells that were treated with SADS-CoV and FIPV nsp1 for RNA sequencing analysis and found that nsp1 had a specific inhibitory effect on interferon (IFN) and cell cycle genes. Using the Renilla luciferase (Rluc) assay and Western blotting, we confirmed that seven representative α-CoVs nsp1s could significantly inhibit the phosphorylation of STAT1-S727 and interfere with the effect of IFN-I. Moreover, the cell cycle experiment confirmed that α-CoVs nsp1 could encourage host cells to stay in the G0/G1 phase. Based on these findings, we not only greatly improved the crystal structure data on α-CoVs nsp1, but we also speculated that α-CoVs nsp1 regulated host proliferation and immune evasion-related biological functions by inhibiting the synthesis of host proteins, thus creating an environment conducive to the virus.

PubMed: 32731335
DOI: 10.3390/v12080812

実験手法

X-RAY DIFFRACTION (1.803 Å)