3PRM

Structural analysis of a viral OTU domain protease from the Crimean-Congo Hemorrhagic Fever virus in complex with human ubiquitin

3PRM の概要

• エントリーDOI: 10.2210/pdb3prm/pdb
• 分子名称: RNA-directed RNA polymerase L, Polyubiquitin-B (Fragment) (3 entities in total)
• 機能のキーワード: ubiquitin hydrolase, deubiquitinase, hydrolase, cysteine protease, viral protein, hydrolase-hydrolase complex, hydrolase/hydrolase
• 由来する生物種: Crimean-Congo hemorrhagic fever virus; 詳細
• 細胞内の位置: Ubiquitin: Cytoplasm : J3QS39
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 58428.16

構造登録者

Capodagli, G.C.,McKercher, M.A.,Baker, E.A.,Masters, E.M.,Brunzelle, J.S.,Pegan, S.D. (登録日: 2010-11-30, 公開日: 2011-01-26, 最終更新日: 2024-11-06)

主引用文献

Capodagli, G.C.,McKercher, M.A.,Baker, E.A.,Masters, E.M.,Brunzelle, J.S.,Pegan, S.D.
Structural analysis of a viral ovarian tumor domain protease from the crimean-congo hemorrhagic Fever virus in complex with covalently bonded ubiquitin.
J.Virol., 85:3621-3630, 2011

PubMed Abstract: Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, single-stranded RNA [ssRNA(-)] nairovirus that produces fever, prostration, and severe hemorrhages in humans. With fatality rates for CCHF ranging up to 70% based on several factors, CCHF is considered a dangerous emerging disease. Originally identified in the former Soviet Union and the Congo, CCHF has rapidly spread across large sections of Europe, Asia, and Africa. Recent reports have identified a viral homologue of the ovarian tumor protease superfamily (vOTU) within its L protein. This protease has subsequently been implicated in downregulation of the type I interferon immune response through cleavage of posttranslational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15). Additionally, homologues of vOTU have been suggested to perform similar roles in the positive-sense, single-stranded RNA [ssRNA(+)] arteriviruses. By utilizing X-ray crystallographic techniques, the structure of vOTU covalently bound to ubiquitin propylamine, a suicide substrate of the enzyme, was elucidated to 1.7 Å, revealing unique structural elements that define this new subclass of the OTU superfamily. In addition, kinetic studies were carried out with aminomethylcoumarin (AMC) conjugates of monomeric Ub, ISG15, and NEDD8 (neural precursor cell expressed, developmentally downregulated 8) substrates in order to provide quantitative insights into vOTU's preference for Ub and Ub-like substrates.

PubMed: 21228232
DOI: 10.1128/JVI.02496-10

実験手法

X-RAY DIFFRACTION (2.3 Å)