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

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.
PDB ID: 4GV3Download
MMDB ID: 109600
PDB Deposition Date: 2012/8/30
Updated in MMDB: 2013/07
Experimental Method:
x-ray diffraction
Resolution: 1.68  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4GV3: trimeric; determined by author and by software (PISA)
Molecular Components in 4GV3
Label Count Molecule
Protein (1 molecule)
Nucleoprotein(Gene symbol: LASVsSgp1)
Molecule annotation
Nucleotides(2 molecules)
RNA (5'-r(*(gtp)p*gp*gp*c)-3')
Molecule annotation
RNA (5'-r(p*cp*gp*cp*cp*c)-3')
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB