3CLpro protein; 3C-Like-proteinase

Description of 3CLpro protein; 3C-Like-proteinase

General information on 3CLpro protein

The 3C-like proteinase also known as 3Clpro is a protein that plays a pivotal role in the maturation of the coronavirus (CoV). CoV are a family of viruses that contain positive strand, enveloped RNA and the largest known viral genome (27-31 kb). CoV is responsible for coronavirus diseases (COVID). COVID virus can affect all cells that express ACE2 protein and is responsible for acute and chronic respiratory, central nervous system and enteric disease in birds, animals and humans. 3CLpro derives from the replicase polyprotein and matures by undergoing autolytic cleavage at both the C-terminal and N-terminal flanking sites. Only the dimer form of 3CLpro protein is active. However, it remains unclear at which point dimerization happens. 3CLpro is believed to regulate the proteolytic processing of two large viral replicase polyproteins pp 1a (450 kDa) and pp lab (750 kDa). The proteolytic processing produces several functional subunits that regulate both the replication and transcription of the viral genome.
3CLpro protein is biologically active only as a dimer while being inactive as a monomer. The N-terminus residue of located between domain II and III of one monomer and the domain II of the other monomer is believed to play an important role in the dimerization of the protein as well as the formation of the active site of 3CLpro. SARS 3CLpro is a homodimer. The protomer of 3CLpro contains three domains. The first two domains contain β-barrels that form a chymotrypsin fold. Domain I consists of residues 8-101 whereas domain II consists of residues 102-184. Domain I and II are connected to the third extra helix domain via a long loop. Domain III contain mainly α-helices. The protein has a catalytic dyad, more precisely His-41 and Cys-145, which located in the deep cleft between these two domains. The substrate or inhibitor binding site is also located in a cleft between the two first domains.

SDS-PAGE for 3CLpro protein; 3C-Like-proteinase