4HXD

Diversity of ubiquitin and ISG15 specificity amongst nairoviruses viral ovarian tumor domain proteases

4HXD の概要

• エントリーDOI: 10.2210/pdb4hxd/pdb
• 分子名称: Polyubiquitin-C, RNA-directed RNA polymerase L, 1.7.6 3-bromanylpropan-1-amine, ... (5 entities in total)
• 機能のキーワード: otu-like cysteine protease, dugbe virus, deubiquitinase, 3-aminopropane, ubiquitin hydrolase, viral protein, hydrolase, ubiquitin., hydrolase-viral protein complex, hydrolase/viral protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Ubiquitin: Cytoplasm : P0CG48
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 57626.57

構造登録者

Capodagli, G.C.,Pegan, S.D. (登録日: 2012-11-09, 公開日: 2013-02-13, 最終更新日: 2024-04-03)

主引用文献

Capodagli, G.C.,Deaton, M.K.,Baker, E.A.,Lumpkin, R.J.,Pegan, S.D.
Diversity of Ubiquitin and ISG15 Specificity among Nairoviruses' Viral Ovarian Tumor Domain Proteases.
J.Virol., 87:3815-3827, 2013

PubMed Abstract: 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.

PubMed: 23345508
DOI: 10.1128/JVI.03252-12

実験手法

X-RAY DIFFRACTION (2.85 Å)