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. 2006 Mar 27;151(9):1841–1851. doi: 10.1007/s00705-006-0744-9

The rubella virus nonstructural protease recognizes itself via an internal sequence present upstream of the cleavage site for trans-activity

H H Chen 1, C J Stark 1, C D Atreya 1
PMCID: PMC7086818  PMID: 16570206

Summary.

The substrate requirement for rubella virus protease trans-activity is unknown. Here, we analyzed the cleavability of RV P200-derived substrates varying in their N-terminal lengths (72–475 amino acids) from the cleavage site by the RV protease trans-activity. Only substrates with at least 309 amino acid residues N-terminal to the cleavage site were able to undergo cleavage. Further, rubella sequence was found to be necessary in the N-terminal region of the substrate, whereas a heterologous sequence C-terminal to the cleavage site was tolerated. These results demonstrated a requirement for residues located between amino acids 994–1102 of the RV P200 polyprotein, besides its cleavage site for RV protease trans-activity. This region overlaps with the starting site of the essential cis-protease activity of RV P200 polyprotein. This is a novel observation for a viral protease of the family Togaviridae.

Keywords: Cleavage Site, Rubella Virus, Protease Domain, Human Embryonic Kidney 293T Cell, Homologous Substrate

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