3Q7C

Exonuclease domain of Lassa virus nucleoprotein bound to manganese

Summary for 3Q7C

• Entry DOI: 10.2210/pdb3q7c/pdb
• Related: 3Q7B
• Descriptor: Nucleoprotein, ZINC ION, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: deddh exonuclease, 3' exonuclease, arenavirus nucleoprotein, hydrolase
• Biological source: Lassa virus (LASV)
• Cellular location: Virion: P13699
• Total number of polymer chains: 1
• Total formula weight: 27485.42

Authors

Hastie, K.M.,Kimberlin, C.R.,Zandonatti, M.A.,MacRae, I.J.,Saphire, E.O. (deposition date: 2011-01-04, release date: 2011-02-09, Last modification date: 2024-02-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.5 Å)