SNAP output for PDB entry 4gv9 [SNAP web server]

PDB-id

4gv9; SNAP-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein-RNA

Method

X-ray (2.46 Å)

Summary

Lassa nucleoprotein c-terminal domain in complex with triphosphated dsrna soaking for 5 min

Reference

Jiang X, Huang Q, Wang W, Dong H, Ly H, Liang Y, Dong C (2013): "Structures of Arenaviral Nucleoproteins with Triphosphate dsRNA Reveal a Unique Mechanism of Immune Suppression." J.Biol.Chem., 288, 16949-16959. doi: 10.1074/jbc.M112.420521.

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.