|PROSITE documentation PDOC51946|
Coronaviruses (CoVs) are enveloped positive-strand RNA viruses that infect many species, including humans, other mammals, and birds. After infection, the host may develop respiratory, bowel, liver, and neurological diseases. Coronaviruses are divided into four genera: αcoronavirus, βcoronavirus, γcoronavirus, and Deltacoronavirus. SARS, SARS-CoV-2, BatCoV RaTG13 and Bat-SARS-like coronavirus (BATSL-CoVZXC21 and BAT-SL-CoVZC45) belong to the Sarbecovirus subgenus of βcoronavirus [E1].
The CoV replicase gene encodes two overlapping polyproteins, termed pp1a and pp1ab, which mediate viral replication and transcription. The polypeptides pp1a and pp1ab are processed by the action of a main protease (Nsp5) (see <PDOC51442>) and of one or two papain-like proteases (PLpro) (see <PDOC51124>) found in Nsp3 into non-structural proteins (Nsps) to form the replication/ transcription complex (RTC). Nsp4 is an approximately 500-amino-acid replicase subunit that is released by the combined activity of the main and papain-like proteases. An N-terminal transmembrane region (amino acids 1-30) is presumably followed by a large lumenal domain (amino acids 30-280), three closely spaced additional transmembrane regions (amino acids 280-400) and finally a C-terminal domain of about 100 residues that is exposed at the cytoplasmic face of the membrane. Nsp4 plays important role in coronavirus replication and double membrane vesicles (DMVs) formation, and the transmembrane regions of Nsp4 are involved in association of the coronavirus replication complex with cellular membranes. The Nsp4C domain could be engaged in protein-protein interactions [1,2].
The Nsp4C structure contains six short β-strands, β1-β6, and four α-helices, α1-α4. Strands β1 and β2 and strands β3 and β5 form small two-stranded antiparallel sheets (see <PDB:3GZF>). Strands β4 and β6 could participate in the formation of a dimer interface or interact with other partner molecules to help to stabilize the Nsp4 molecule. Nsp4C has nine conserved and two nonconserved residues which form the hydrophobic core of the structure [1,2].
The profile we developed covers the entire CoV Nsp4C domain.Last update:
October 2020 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Xu X. Lou Z. Ma Y. Chen X. Yang Z. Tong X. Zhao Q. Xu Y. Deng H. Bartlam M. Rao Z.|
|Title||Crystal structure of the C-terminal cytoplasmic domain of non-structural protein 4 from mouse hepatitis virus A59.|
|Source||PLoS One. 4:E6217-E6217(2009).|
|2||Authors||Manolaridis I. Wojdyla J.A. Panjikar S. Snijder E.J. Gorbalenya A.E. Berglind H. Nordlund P. Coutard B. Tucker P.A.|
|Title||Structure of the C-terminal domain of nsp4 from feline coronavirus.|
|Source||Acta Crystallogr. D. Biol. Crystallogr. 65:839-846(2009).|