Structural domains comprising this superfamily share the structure of the N-terminal nuclease domain of the nsp1beta protein encoded by the Porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV contains a single-stranded, positive-sense RNA genome that carries nine open reading frames (ORFs). Entry into host cells is followed by the release of the genome into the cytoplasm and the expression of the large replicase gene, consisting of ORFs 1a and 1b. Subsequent translation yields two multidomain replicase polyproteins, pp1a and pp1ab, with the latter being a C-terminally extended version of the former due to a ribosomal frameshift mechanism. These polyproteins are predicted to be cleaved into 14 nonstructural proteins (nsps) by the nsp4 3C-like main protease and three accessory proteinases residing in nsp1 (including nsp1alpha and nsp1beta) and nsp2. Nsp1 is a multifunctional protein which contains two papain-like cysteine proteases, designated PCPalpha and -beta, and a zinc finger motif required for subgenomic mRNA (sg mRNA) transcription. Sequence analyses revealed that nsp1alpha contains the N-terminal zinc finger and PCPalpha, while nsp1beta contains PCPbeta.

Structural and mutational studies have revealed that PRRSV nsp1beta, the second protein in the pp1a polyprotein encoded by PRRSV, is essential for viral RNA synthesis and virulence. nsp1beta consists of an NTD, which shows a strict metal ion-dependent nuclease activity on ssRNA and dsDNA; a C-terminal PCP domain, that is able to release the protein from the downstream nsp2 protein; a C-terminal extension (CTE), which exemplifies the substrate binding to the proteolytic catalytic site during self-processing; and a linker connecting the NTD and the PCP domains, which also contributes to nsp1beta homodimer formation PMID:20410261.