PROSITE documentation PDOC51690

Alphavirus core protein (CP) domain profile

Togaviruses are enveloped animal viruses containing a single-stranded RNA-genome of positive polarity [E1]. They can cause a variety of diseases, such as encephalitis, fever, arthritis and rash. Togaviruses of the αvirus group consist of a nucleoprotein core, a lipid membrane bilayer which envelopes the core, and glycoprotein spikes on the surface of the membrane. The core contains the genomic RNA and the core protein (CP). CP is located at the N-terminal end of the viral structural polyprotein, which is translated from a subgenomic RNA. It is followed in the polyprotein by the E3-E2-6K-E1 proteins. At the first step in the post-translational processing of this polyprotein, CP acts as a cis proteinase to auto-catalytically cleave itself from the rest of the polyprotein. Biologically CP functions as a proteolytic enzyme only once, in the auto-catalytic cleavage at Trp. Thereafter it is auto-inhibited by the presence of the Trp side-chain in the substrate-binding pocket [1,2,3]. The αvirus CP forms peptidase family S3 [2,E2].

The polypeptide backbone fold of CP is similar to that of the chymotrypsin family of serine proteinases. The structure consists of two similar "Greek key" β-barrel sub-domains, formed with the N- and the C-terminal halves of the protein (see <PDB:2SNV>). The active site is in a cleft between these two sub-domains. Ser, His and Asp form the catalytic triad. The aminoacid sequence Gly-Asp-Ser-Gly, which is conserved among all the chymotrypsin-like serine proteases and contains the catalytically essential Ser is also present in CP [1,2,3].

The profile we developed covers the entire αvirus CP domain.