Human Coronavirus Nucleocapsid Protein

What is Nucleocapsid Protein?

The nucleocapsid protein (N-protein) is the most abundant protein in coronavirus. The N-protein is a highly immunogenic phosphoprotein, and it is normally very conserved. The N protein of coronavirus is often used as a marker in diagnostic assays. During virion assembly, N protein binds to viral RNA and leads to formation of the helical nucleocapsid. The abundance and high hydrophilicity of N protein are supposed to contribute to potent immunity after coroanvirus infection.

Nucleocapsid Protein Function

The N protein constitutes the only protein present in the nucleocapsid. It is composed of two separate domains, an N-terminal domain (NTD) and a C-terminal domain (CTD), both capable of binding RNA in vitro, but each domain uses different mechanisms to bind RNA.

N protein is also heavily phosphorylated, and phosphorylation has been suggested to trigger a structural change enhancing the affinity for viral versus non-viral RNA.

N protein binds the viral genome in a beads-on-a-string type conformation. Two specific RNA substrates have been identified for N protein; the TRSs and the genomic packaging signal. The genomic packaging signal has been found to bind specifically to the second, or C-terminal RNA binding domain.

N protein also binds nsp3, a key component of the replicase complex, and the M protein. These protein interactions likely help tether the viral genome to the replicase-transcriptase complex (RTC), and subsequently package the encapsidated genome into viral particles.
(Ref: Anthony R. Fehr and Stanley Perlman.Coronaviruses: An Overview of Their Replication and Pathogenesis.Methods Mol Biol. 2015)