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PDBsum entry 5tl7
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Signaling protein/hydrolase
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PDB id
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5tl7
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References listed in PDB file
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Key reference
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Title
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Structural insights into the interaction of coronavirus papain-Like proteases and interferon-Stimulated gene product 15 from different species.
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Authors
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C.M.Daczkowski,
J.V.Dzimianski,
J.R.Clasman,
O.Goodwin,
A.D.Mesecar,
S.D.Pegan.
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Ref.
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J Mol Biol, 2017,
429,
1661-1683.
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PubMed id
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Abstract
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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.
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