Diversity of Ubiquitin and ISG15 Specificity among Nairoviruses' Viral Ovarian Tumor Domain Proteases
| Autor: | Michelle K. Deaton, Glenn C. Capodagli, Erica A. Baker, Scott D. Pegan, Ryan J. Lumpkin |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Proteases Protein Conformation Virulence Factors Molecular Sequence Data Immunology Electrophoretic Mobility Shift Assay Sequence alignment Crystallography X-Ray Microbiology Substrate Specificity Viral Proteins Protein structure Species Specificity Ubiquitin Virology Amino Acid Sequence Ubiquitins Peptide sequence Gene Genetics Nairovirus biology biology.organism_classification ISG15 Insect Science Mutagenesis Site-Directed biology.protein Cytokines Pathogenesis and Immunity Sequence Alignment Peptide Hydrolases |
| Zdroj: | Journal of Virology |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.03252-12 |
| Popis: | Nairoviruses are responsible for numerous diseases that affect both humans and animal. Recent work has implicated the viral ovarian tumor domain (vOTU) as a possible nairovirus virulence factor due to its ability to edit ubiquitin (Ub) bound to cellular proteins and, at least in the case of Crimean-Congo hemorrhagic fever virus (CCHFV), to cleave the Ub-like protein interferon-stimulated gene 15 (ISG15), a protein involved in the regulation of host immunity. The prospective roles of vOTUs in immune evasion have generated several questions concerning whether vOTUs act through a preserved specificity for Ub- and ISG15-conjugated proteins and where that specificity may originate. To gain insight into the substrate specificity of vOTUs, enzymological studies were conducted on vOTUs from Dugbe, CCHFV, and Erve nairoviruses. These studies revealed that vOTUs originating from different nairoviruses display a significant divergence in their preference toward Ub and ISG15. In addition, a recently identified vOTU from turnip yellow mosaic tymovirus was evaluated to elucidate any possible similarities between vOTUs originating from different viral families. Although possessing a similar preference for certain polymeric Ub moieties, its activity toward Ub in general was significantly less then those of nairoviruses. Lastly, the X-ray crystallographic structure of the vOTU from the Dugbe nairovirus was obtained in complex with Ub to reveal structural commonalities of vOTUs originating from nairoviruses. The structure suggests that divergences between nairovirus vOTUs specificity originate at the primary structural level. Comparison of this structure to that originating from CCHFV identified key residues that infer the substrate specificity of vOTUs. |
| Databáze: | OpenAIRE |
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