FIGURE 10.
Proposed model for polyprotein processing in MERS-CoV regulated by ligand-induced dimerization of MERS-CoV 3CLpro. MERS-CoV 3CLpro domains I and II are together represented as the rectangular box, and domain III is represented as a cylinder. The N and C termini are labeled, and the yellow cylinder labeled S represents a ligand that can be a peptide inhibitor, peptide substrate, or 3CLpro cleavage sites in the polyprotein. Various steps required for the auto-release of 3CLpro from the polyprotein and subsequent processing of the polyprotein cleavage sites are described in the text. Suggested by our AUC and kinetic studies, the shaded region (steps 5 and 6) highlights the additional steps MERS-CoV 3CLpro would undertake during polyprotein processing and have been described in the kinetic model depicted in Fig. 5B.