Journal:Acta Cryst D:S2059798318015322

Structure of ISG15 from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement

Caroline Langley, Octavia Goodwin, John V. Dzimianski, Courtney M. Daczkowski and Scott D. Pegan ^[1]

Molecular Tour
Ubiquitin-like interferon-stimulated gene product 15 (ISG15) is a key modulator of interferon responses involved in the innate immune system. This 15 kDa protein is comprised of two ubiquitin (Ub)-like β-grasp three-dimensional folds. Post-translational modifications of viral proteins introduced by ISG15 have been directly observed to affect the function of numerous viral proteins. While ubiquitin is essentially identical across all animals, comparison of ISG15 across species reveals they are relatively divergent, with sequence identity dropping as low as ~58% among mammals. These ISG15 species-species differences have also long been shown to impact viral deISGylase function.

Recently, the structure of the first non-human ISG15 originating from mouse suggested that human structures of ISG15s may not be reflective of other species. Here, the structure of ISG15 from the bat species Myotis davidii solved to 1.37 Å is reported. Comparison of this ISG15 structure with those of human and mouse not only underscores the structural impact of ISG15 species-species differences, but also highlights a conserved hydrophobic motif formed between the two domains of ISG15. Using papain-like deISGylase from the severe acute respiratory coronavirus as a probe, the biochemical importance of this interface and its species-species variances on ISG15-protein engagements was illuminated.

References

1. ↑ Langley C, Goodwin O, Dzimianski JV, Daczkowski CM, Pegan SD. Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement. Acta Crystallogr D Struct Biol. 2019 Jan 1;75(Pt 1):21-31. doi:, 10.1107/S2059798318015322. Epub 2019 Jan 4. PMID:30644842 doi:http://dx.doi.org/10.1107/S2059798318015322