4GV3

Structures of Lassa and Tacaribe viral nucleoproteins with or without 5 triphosphate dsRNA substrate reveal a unique 3 -5 exoribonuclease mechanism to suppress type I interferon production

4GV3 の概要

• エントリーDOI: 10.2210/pdb4gv3/pdb
• 関連するPDBエントリー: 3MWP 4G9Z
• 分子名称: RNA (5'-R(*(GTP)P*GP*GP*C)-3'), RNA (5'-R(P*CP*GP*CP*CP*C)-3'), Nucleoprotein, ... (6 entities in total)
• 機能のキーワード: ddedh family, 3'-5'exoribonuclease, rna binding protein-rna complex, rna binding protein/rna
• 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: 3
• 化学式量合計: 27167.80

構造登録者

Jiang, X.,Huang, Q.,Wang, W.,Dong, H.,Ly, H.,Liang, Y.,Dong, C. (登録日: 2012-08-30, 公開日: 2013-05-01, 最終更新日: 2024-02-28)

主引用文献

Jiang, X.,Huang, Q.,Wang, W.,Dong, H.,Ly, H.,Liang, Y.,Dong, C.
Structures of Arenaviral Nucleoproteins with Triphosphate dsRNA Reveal a Unique Mechanism of Immune Suppression.
J.Biol.Chem., 288:16949-16959, 2013

PubMed Abstract: A hallmark of severe Lassa fever is the generalized immune suppression, the mechanism of which is poorly understood. Lassa virus (LASV) nucleoprotein (NP) is the only known 3'-5' exoribonuclease that can suppress type I interferon (IFN) production possibly by degrading immune-stimulatory RNAs. How this unique enzymatic activity of LASV NP recognizes and processes RNA substrates is unknown. We provide an atomic view of a catalytically active exoribonuclease domain of LASV NP (LASV NP-C) in the process of degrading a 5' triphosphate double-stranded (ds) RNA substrate, a typical pathogen-associated molecular pattern molecule, to induce type I IFN production. Additionally, we provide for the first time a high-resolution crystal structure of an active exoribonuclease domain of Tacaribe arenavirus (TCRV) NP. Coupled with the in vitro enzymatic and cell-based interferon suppression assays, these structural analyses strongly support a unified model of an exoribonuclease-dependent IFN suppression mechanism shared by all known arenaviruses. New knowledge learned from these studies should aid the development of therapeutics against pathogenic arenaviruses that can infect hundreds of thousands of individuals and kill thousands annually.

PubMed: 23615902
DOI: 10.1074/jbc.M112.420521

実験手法

X-RAY DIFFRACTION (1.68 Å)