Coronavirus nucleocapsid protein

The nucleocapsid (N) protein is a protein that packages the positive-sense RNA genome of coronaviruses to form ribonucleoprotein structures enclosed within the viral capsid. In addition to its interactions with RNA, N forms protein-protein interactions with the coronavirus membrane protein (M) during the process of viral assembly. N also has additional functions in manipulating the cell cycle of the host cell. The N protein is highly immunogenic, with antibodies to the N protein found in the majority of patients recovered from SARS and COVID-19. In COVID-19 specifically, the rate at which patients develop anti-N antibodies is estimated at 80%. This proportion varies depending on the measurement methodology utilized and typically increases in correlation with disease severity.

Structure

The N protein is composed of two protein domains connected by an intrinsically disordered region (IDR) known as the linker region, with additional disordered segments at each terminus. A third small domain at the C-terminal tail appears to have an ordered alpha helical secondary structure and may be involved in the formation of higher-order oligomeric assemblies. In SARS-CoV, the causative agent of SARS, the N protein is 422 amino acid residues long and in SARS-CoV-2, the causative agent of COVID-19, it is 419 residues long.

Both the N-terminal and C-terminal domains are capable of binding RNA. The C-terminal domain forms a dimer that is likely to be the native functional state.