PROSITE documentation PDOC51921

Betacoronavirus spike (S) glycoprotein S1 subunit C-terminal (CTD) domain profile

Coronaviruses (CoVs) primarily cause respiratory and enteric diseases in humans, animals, and birds, and some CoVs also cause systemic diseases, including hepatitis or neurological diseases. Phylogenetically, CoVs are divided into four genera, called the α-, β-, γ-, and delta-CoVs. Of these, βcoronaviruses (βCoVs) [E1] have attracted attention worldwide because of their pathogenic capacity and potential to cause a global pandemic of human infections and the widespread existence of an enormous number of species in bats. Three highly pathogenic human coronaviruses (CoVs) have been identified so far, including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and a 2019 novel coronavirus SARS-CoV-2 [1,2,3].

A coronavirus contains four structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. Among them, the S protein, which is located on the envelope surface of the virion, functions to mediate receptor recognition and membrane fusion and is therefore a key factor determining the virus tropism for a specific species. In most cases, coronaviral S will be further cleaved into S1 and S2 subunits, and the receptor binding capacity is allocated to the S1 subunit. The receptor binding domain (RBD) of βCoV that directly engages the receptor is commonly located in the C-terminal half of S1 [C-terminal domain (CTD)] such as in SARS-CoV, SARS-CoV-2, MERS-CoV,and BatCoV HKU4, though in rare cases such as with mouse hepatitis virus (MHV), the RBD region was identified in the S1 N-terminal domain (NTD) [1,2,3].

The βCoV S1-CTD domain is composed of a core and an external subdomain (see <PDB:5GYQ>). During evolution, the core subdomain is structurally preserved, whereas the external subdomain folds into variant structures to engage different receptors. The most conserved part lies in the core-center sheet that is composed of five antiparallel strands and functions as the scaffold of the core subdomain. Additional conserved elements include the core-center helices and core-peripheral structures. Characteristic cysteine residues form three disulfide bonds in the core subdomain, further stabilizing the core structure from the interior [1].

The profile we developed covers the entire βCoV S1-CTD domain.