PROSITE documentation PDOC51928

Coronavirus nucleocapsid (CoV N) protein N- and C-terminal (NTD and CTD) domains profiles

Coronaviruses (CoVs) [E1] are a diverse group of enveloped, plus-stranded RNA viruses that infect humans and many animal species, in which they can cause respiratory, enteric, hepatic, central nervous system and neurological diseases of varying severity. The main CoV structural proteins are S (spike) (see <PDOC51923>), E (envelope) (see <PDOC51926>), M (membrane) (see <PDOC51927>), and N (nucleocapsid), where S, E, and M are integral membrane proteins. The N protein serves multiple purposes, such as packaging the RNA genome into helical ribonucleoproteins, modulating host cell metabolism, and regulating viral RNA synthesis during replication and transcription. The CoV N protein is a non-specific nucleic acid-binding protein. It has been shown to bind to single-stranded RNA (ssRNA), single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). The N protein binds to the viral RNA genome, forming a long helical nucleocapsid structure or ribonucleoprotein (RNP) complex. Upon infection, the N protein enters the host cell with the ribonucleoprotein core and is able to interact with a number of host proteins [1,2,3,4,5,6,7,8,9].

CoV N proteins contain two structured domains: the N-terminal domain (NTD; also called RBD), which is responsible for RNA binding, and the C-terminal domain (CTD; also called DD), which mediates oligomerization and RNA binding. The NTD and CTD form two independent domains that do not interact with each other. These domains are connected by a relatively long linker that is likely to be unstructured, and additional unstructured regions are located at the N and C termini. Together, the structured domains and unstructured regions of N protein participate in nucleic acid binding and subsequent steps of nucleocapsid formation. The N protein dimerizes via its C-terminal domain, providing a platform to recruit viral RNA; the prominent NTD is responsible for recruiting specific or non-specific RNAs; the linkers between NTD and CTD may act as a flexible arm to change the relative position of the two domains.

The CoV N NTD fold consists of a five-stranded, antiparallel β-sheet with the topology β4-β2-β3-β1-β5, partially encapsulated within extended, intertwining loops and turns connecting the β-strands (see <PDB:5N4K>). The CTD of CoV N exists in dimeric form. Each CoV N CTD monomer contains five α-helices, three 3(10) helices, and two β-strands and assumes a α1-4β1-β2-α5 topology (see <PDB:5EPW>) [5,6,7,8,9].

The profiles we developed cover the entire CoV N protein N- and C-terminal domains.