Human interferon-stimulated gene 15 protein (ISG15), also called ubiquitin cross-reactive protein (UCRP), is the first identified ubiquitin-like protein containing two ubiquitin-like domains fused in tandem. The active form of ISG15 is conjugated to target proteins via the C-terminal glycine residue through an isopeptide bond in a manner similar to ubiquitin. The biological role of ISG15 is strongly associated with the modulation of cell immune function, and there is mounting evidence suggesting that many viral pathogens evade the host innate immune response by interfering with ISG15 conjugation to both host and viral proteins in a variety of ways. Here we report nearly complete backbone 1HN, 15N, 13C′, and 13Cα, as well as side chain 13Cβ, methyl (Ile-δ1, Leu, Val), amide (Asn, Gln), and indole N–H (Trp) NMR resonance assignments for the 157-residue human ISG15 protein. These resonance assignments provide the basis for future structural and functional solution NMR studies of the biologically important human ISG15 protein.
Backbone NMR resonance assignment Human ISG15 Innate immune response Ubiquitin-like protein
Chemical shift index
Heteronuclear single quantum coherence
Interferon-stimulated gene 15
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This work was supported by National Institute of General Medical Sciences Protein Structure Initiative Grants U54-GM074958 and U54-GM094597 (to G.T.M.) and National Institutes of Allergy and Infectious Disease Grant AI11772 (to R.M.K.). The authors wish to thank Dr. David S. Waugh for kindly providing plasmid pKM596 and the BL21PRO cells. NMR spectra at 750 MHz were acquired in the Environmental Molecular Sciences Laboratory (a national scientific user facility sponsored by the U.S. Department of Energy Office of Biological and Environmental Research) located at Pacific Northwest National Laboratory and operated for DOE by Battelle (contract KP130103).
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