| Primary Identifier | IPR023183 | Type | Homologous_superfamily |
| Short Name | Chymotrypsin-like_C |
| description | The replicase polyprotein 1ab is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products. Nsp1 is essential for viral subgenomic mRNA synthesis. Nsp2 cysteine proteinase which cleaves the Nsp2/Nsp3 site in the polyprotein. Also displays deubiquitinating and deISGylase activities. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent host innate immunity. The 3C-like serine proteinase chain (Nsp4) is responsible for the majority of cleavages as it cleaves the C terminus of the polyprotein. The helicase chain, which contains a zinc finger structure, displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity [].This superfamily represents the C-terminal domain of chymotrypsin-like serine proteinase Nsp4. Nsp4 contains two β-barrels, known as N- and C-terminal barrels, as well as a unique C-terminal domain. The C-terminal domain consists of two short pairs of β-strands and two α-helices. It interacts with the C-terminal barrel through an interface consisting of conserved hydrophobic residues: Leu-105 and Leu-112 from the C-terminal β-barrel and Val-158, Leu-163, Phe-167, Ile-182, Leu-196, and Ile-197 from the C-terminal domain. There is also an exposed patch of conserved solvent-exposed hydrophobic residues that may form part of the interface with Nsp5 in the Nsp4-5 intermediate []. This hydrophobic patch may also mediate interactions with Nsp2, which associates with Nsp3-8 to induce cleavage of the Nsp4-5 site by Nsp4 []. The C-terminal domain can clearly adopt different orientations relative to the two β-barrels, which may facilitate substrate binding or autoproteolysis []. |
