Structural and functional characterization of MERS coronavirus papain-like protease

BACKGROUNDS: A new highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and Saudi Arabia and quickly spread to some European countries since September 2012. Until 15 May 2014, it has infected at least 572 people with a fatality rate of about 30% globally. Studies to understand the virus and to develop antiviral drugs or therapy are necessary and urgent. In the present study, MERS-CoV papain-like protease (PL(pro)) is expressed, and its structural and functional consequences are elucidated. RESULTS: Circular dichroism and Tyr/Trp fluorescence analyses indicated that the secondary and tertiary structure of MERS-CoV PL(pro) is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PL(pro) is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PL(pro) exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PL(pro). A natural mutation, Leu105, is the major reason for this difference. CONCLUSIONS: Overall, MERS-CoV PL(pro) bound by an endogenous metal ion shows a folded structure and potent proteolytic and deubiquitination activity. These findings provide important insights into the structural and functional properties of coronaviral PL(pro) family, which is applicable to develop strategies inhibiting PL(pro) against highly pathogenic coronaviruses.