Oligomerization of the carboxyl terminal domain of the human coronavirus 229E nucleocapsid protein

The coronavirus (CoV) N protein oligomerizes via its carboxyl terminus. However, the oligomerization mechanism of the C-terminal domains (CTD) of CoV N proteins remains unclear. Based on the protein disorder prediction system, a comprehensive series of HCoV-229E N protein mutants with truncated CTD was generated and systematically investigated by biophysical and biochemical analyses to clarify the role of the C-terminal tail of the HCoV-229E N protein in oligomerization. These results indicate that the last C-terminal tail plays an important role in dimer–dimer association. The C-terminal tail peptide is able to interfere with the oligomerization of the CTD of HCoV-229E N protein and performs the inhibitory effect on viral titre of HCoV-229E. This study may assist the development of anti-viral drugs against HCoV.Structured summary of protein interactionsN and C-terminal tail peptidebind by cosedimentation in solution (View interaction)N and Nbind by cosedimentation in solution (View Interaction: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)C-terminal tail peptide and Nbind by fluorescence technology (View interaction)N and Nbind by cross-linking study (View interaction)N and Nbind by cross-linking study (View Interaction: 1, 2, 3, 4)

► The role of the C-terminal tail of the HCoV-229E N protein in oligomerization.
► A correlation between oligomerization and thermostability.
► The C-terminal tail peptide interferes with the oligomerization.
► The development of drugs to disrupt the oligomerization of the viral N protein.