Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species. Issue 11 (2nd June 2017)

• Record Type: Journal Article
• Authors: Daczkowski, Courtney M.; Dzimianski, John V.; Clasman, Jozlyn R.; Goodwin, Octavia; Mesecar, Andrew D.; Pegan, Scott D.
• Is Part Of: Journal of molecular biology. Volume 429:Issue 11(2017)
• Page Start: 1661
• Page End: 1683
• Publication Date: 2017-06-02
• Subjects: CoV Coronavirus -- SARS-CoV severe acute respiratory syndrome CoV -- MERS-CoV Middle East respiratory syndrome CoV -- PLP Papain-like protease (for viruses that have more than one PLpro) -- PLpro Papain-like protease -- MHV mouse hepatitis virus -- Ub ubiquitin -- USP Ub-specific protease -- DUB deubiquitinating enzyme -- Ubl Ub-like -- ISG15 interferon-stimulated gene product 15 -- IFN type-I interferon -- mISG15 mouse ISG15 -- vOTUs viral ovarian tumor domain proteases -- hISG15 human ISG15 -- ITC isothermal titration calorimetry -- CmISG15 C-terminal domain of ISG15 from mouse -- ChISG15 C-terminal domain of ISG15 from human -- DSSP Define Secondary Structure of Proteins -- BME β-mercaptoethanol -- AMC 7-amino-4-methylcoumarin -- PEG polyethylene glycol; ISG15 -- ubiquitin -- coronavirus -- Middle East respiratory syndrome -- severe acute respiratory syndrome; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2017.04.011
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication and antagonize the host innate immune response. The latter function involves reversing the post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon-stimulated gene product 15 (ISG15). Ub is known to be highly conserved among eukaryotes, but surprisingly, ISG15 is highly divergent among animals. The ramifications of this sequence divergence to the recognition of ISG15 by coronavirus PLPs at a structural and biochemical level are poorly understood. Therefore, the activity of PLPs from SARS-CoV, MERS‐CoV, and mouse hepatitis virus was evaluated against seven ISG15s originating from an assortment of animal species susceptible, and not, to certain coronavirus infections. Excitingly, our kinetic, thermodynamic, and structural analysis revealed an array of different preferences among PLPs. Included in these studies is the first insight into a coronavirus PLP's interface with ISG15 via SARS-CoV PLpro in complex with the principle binding domain of human ISG15 (hISG15) and mouse ISG15s (mISG15s). The first X-ray structure of the full-length mISG15 protein is also reported and highlights a unique, twisted hinge region of ISG15 that is not conserved in hISG15, suggesting a potential role in differential recognition. Taken together, this new information provides a structural and biochemical understanding of the distinct specificities among coronavirus PLPs observed and addresses a critical gap of how PLPs can interact with ISG15s from a wide variety of species. Graphical Abstract: Highlights: Coronavirus PLPs possess immune modulating deubiquitinating/deISGylating activity. Different species' ISG15s have different binding characteristics with PLPs. New structures of PLPs with an ISG15 domain expose different binding orientations. A structure of full-length mISG15 reveals overall differences from hISG15. ISG15 variation affects PLP function and potentially host immune responses.