5TL7

Crystal structure of SARS-CoV papain-like protease in complex with C-terminal domain mouse ISG15

Summary for 5TL7

• Entry DOI: 10.2210/pdb5tl7/pdb
• Related: 5TL6 5TLA
• Descriptor: Ubiquitin-like protein ISG15, Replicase polyprotein 1ab, ZINC ION, ... (4 entities in total)
• Functional Keywords: signaling protein, hydrolase, signaling protein-hydrolase complex, signaling protein/hydrolase
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 4
• Total formula weight: 90311.46

Authors

Daczkowski, C.D.,Dzimianski, J.V.,Pegan, S.D. (deposition date: 2016-10-10, release date: 2017-05-03, Last modification date: 2024-10-16)

Primary citation

Daczkowski, C.M.,Dzimianski, J.V.,Clasman, J.R.,Goodwin, O.,Mesecar, A.D.,Pegan, S.D.
Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species.
J. Mol. Biol., 429:1661-1683, 2017

PubMed 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.

PubMed: 28438633
DOI: 10.1016/j.jmb.2017.04.011

Experimental method

X-RAY DIFFRACTION (2.44 Å)