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Open Access Highly Accessed Research

Structural and functional characterization of MERS coronavirus papain-like protease

Min-Han Lin1, Shang-Ju Chuang1, Chiao-Che Chen1, Shu-Chun Cheng1, Kai-Wen Cheng1, Chao-Hsiung Lin1, Chiao-Yin Sun2* and Chi-Yuan Chou1*

Author Affiliations

1 Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan

2 Department of Nephrology, Chang-Gung Memorial Hospital, Keelung 204, Taiwan

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Journal of Biomedical Science 2014, 21:54  doi:10.1186/1423-0127-21-54

Published: 4 June 2014

Abstract

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 (PLpro) 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 PLpro is well organized and folded. Analytical ultracentrifugation analyses demonstrated that MERS-CoV PLpro is a monomer in solution. The steady-state kinetic and deubiquitination activity assays indicated that MERS-CoV PLpro exhibits potent deubiquitination activity but lower proteolytic activity, compared with SARS-CoV PLpro. A natural mutation, Leu105, is the major reason for this difference.

Conclusions

Overall, MERS-CoV PLpro 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 PLpro family, which is applicable to develop strategies inhibiting PLpro against highly pathogenic coronaviruses.

Keywords:
MERS coronavirus; Papain-like protease; Deubiquitination; Antiviral target