3Q7C

Exonuclease domain of Lassa virus nucleoprotein bound to manganese

3Q7C の概要

• エントリーDOI: 10.2210/pdb3q7c/pdb
• 関連するPDBエントリー: 3Q7B
• 分子名称: Nucleoprotein, ZINC ION, MANGANESE (II) ION, ... (5 entities in total)
• 機能のキーワード: deddh exonuclease, 3' exonuclease, arenavirus nucleoprotein, hydrolase
• 由来する生物種: Lassa virus (LASV)
• 細胞内の位置: Virion: P13699
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27485.42

構造登録者

Hastie, K.M.,Kimberlin, C.R.,Zandonatti, M.A.,MacRae, I.J.,Saphire, E.O. (登録日: 2011-01-04, 公開日: 2011-02-09, 最終更新日: 2024-02-21)

主引用文献

Hastie, K.M.,Kimberlin, C.R.,Zandonatti, M.A.,Macrae, I.J.,Saphire, E.O.
Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3' to 5' exonuclease activity essential for immune suppression.
Proc.Natl.Acad.Sci.USA, 108:2396-2401, 2011

PubMed Abstract: Lassa fever virus, a member of the family Arenaviridae, is a highly endemic category A pathogen that causes 300,000-500,000 infections per year in Western Africa. The arenaviral nucleoprotein NP has been implicated in suppression of the host innate immune system, but the mechanism by which this occurs has remained elusive. Here we present the crystal structure at 1.5 Å of the immunosuppressive C-terminal portion of Lassa virus NP and illustrate that, unexpectedly, its 3D fold closely mimics that of the DEDDh family of exonucleases. Accompanying biochemical experiments illustrate that NP indeed has a previously unknown, bona fide exonuclease activity, with strict specificity for double-stranded RNA substrates. We further demonstrate that this exonuclease activity is essential for the ability of NP to suppress translocation of IFN regulatory factor 3 and block activation of the innate immune system. Thus, the nucleoprotein is a viral exonuclease with anti-immune activity, and this work provides a unique opportunity to combat arenaviral infections.

PubMed: 21262835
DOI: 10.1073/pnas.1016404108

実験手法

X-RAY DIFFRACTION (1.5 Å)