Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 466, Issue 1, Pages 8-14Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2007.07.006
Keywords
severe acute respiratory syndrome; coronavirus; papain-like protease; deubiquitination; ubiquitin; ISG15; specificity
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The severe acute respiratory syndrome coronavirus papain-like protease (SARS-CoV PLpro) carries out N-terminal processing of the viral replicase polyprotein, and also exhibits Lys48-linked polyubiquitin chain debranching and ISG15 precursor processing activities in vitro. Here, we used SDS-PAGE and fluorescence-based assays to demonstrate that ISG15 derivatives are the preferred substrates for the deubiquitinating activity of the PLpro. With k(cat)/K-M of 602,000 M-1 s(-1), PLpro hydrolyzes ISG15-AMC 30- and 60-fold more efficiently than Ub-AMC and Nedd8-AMC, respectively. Data obtained with truncated ISG 15 and hybrid Ub/ISG 15 substrates indicate that both the N- and C-terminal Ub-like domains of ISG15 contribute to this preference. The enzyme also displays a preference for debranching Lys48- over Lys63-linked polyubiquitin chains. Our results demonstrate that SARS-CoV PLpro can differentiate between ubiquitin-like modifiers sharing a common C-terminal sequence, and that the debranching activity of the PLpro is linkage type selective. The potential structural basis for the demonstrated specificity of SARS-CoV PLpro is discussed. Crown copyright (c) 2007 Published by Elsevier Inc. All rights reserved.
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