PROSITE documentation PDOC51889

Rubella virus (RUBV) nonstructural (NS) protease domain profile

Rubella is an infectious disease that is well characterized by rashes. It is often confused with measles that also cause rashes. Confoundingly, rubella is also known as German measles, and measles is also known as rubeola. However, rubella and measles are different diseases caused by different viruses. The Rubella virus (RUBV) is the etiological agent of the Rubella disease and belongs to the genus, Rubivirus [E1], of the newly created family, Matonaviridae [E2]. RUBV is a group VI virus with a single-stranded positive-sense RNA genome enclosed by an icosahedral capsid. The RUBV genome contains two open reading frames (ORFs) encoding five proteins after postranslational proteolytic processing; two proteins (P150 and P90) involved in viral replication are translated from the nonstructural protein ORF (NSP-ORF) and the three structural proteins that form the virus particle are translated from the structural protein ORF (ST-ORF). A cysteine protease domain situated at the C-terminus of P150 and immediately upstream from the cleavage site within the NS-ORF precursor (P200) is responsible for self-cleavage of P200 into P150 and P90. This protease domain, termed the NS protease or RUBV protease (RubPro) domain, is a papain-like protease with catalytic dyad of Cys and His that requires divalent ions like Zn(2+), Co(2+), and Cd(2+) for protease activity. The NS protease domain contains an EF-hand Ca(2+) binding motif, which plays a structural role in stabilizing the protease at physiological temperatures, as well as a structural Zn(2+) binding site coordinated by four cysteines, which is necessary for protease activity. The RUBV NS protease domain forms peptidase family C27 [E3] of clan CA [1,2,3,4,5].

The NS protease domain adopts a unique right-hand architecture with two Zn(2+)-binding sites and a catalytic Cys-His dyad. The fingers, palm, and thumb subdomains correspond to the N-terminal, middle, and C-terminal regions of the NS protease domain, respectively. The fingers subdomain consists of three short parallel β-sheets and four α-helices. Three Cys and a His coordinate a Zn(2+) ion near β3. Next, the palm domain consists of four α-helices, with the catalytic Cys found on α5. Four Cys coordinate a Zn(2+) ion near α6. Finally, the thumb domain consists of five β-sheets with the other catalytic residue, a His, on β7 (see <PDB:7FAV>) [5].

The profile we developed covers the entire RUBV NS protease domain.