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DNA Sequencing> | … For expression in human cells, PLpro sequences were codon-optimized for human expression, synthesized, and cloned into KpnI and XhoI sites of pcDNA3.1(+)-C-DYK for expression with a C-terminal FLAG tag (Genscript). All mutations were introduced by site-directed … | Get A Quote |
The SARS-CoV-2 papain-like protease (PLpro) is a target for antiviral drug development. It is essential for processing viral polyproteins for replication and functions in host immune evasion by cleaving ubiquitin (Ub) and ubiquitin-like protein (Ubl) conjugates. While highly conserved, SARS-CoV-2 and SARS-CoV PLpro have contrasting Ub/Ubl substrate preferences. Using a combination of structural analyses and functional assays, we identify a molecular sensor within the S1 Ub-binding site of PLpro that serves as a key determinant of substrate specificity. Variations within the S1 sensor specifically alter cleavage of Ub substrates but not of the Ubl interferon-stimulated gene 15 protein (ISG15). Significantly, a ... More