PDBsum entry 3q7c

Hydrolase

PDB id

3q7c

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Contents

			Protein chain

					209 a.a. *

			Ligands

					PO4

			Metals

					_ZN


					_MN

			Waters ×306

* Residue conservation analysis

PDB id:

3q7c

Links

Name:

Hydrolase

Title:

Exonuclease domain of lassa virus nucleoprotein bound to manganese

Structure:

Nucleoprotein. Chain: a. Synonym: nucleocapsid protein, protein n. Engineered: yes

Source:

Lassa virus. Lasv. Organism_taxid: 11622. Strain: mouse/sierra leone/josiah/1976. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.50Å

R-factor:

0.191

R-free:

0.216

Authors:

K.M.Hastie,C.R.Kimberlin,M.A.Zandonatti,I.J.Macrae,E.O.Saphire

Key ref:

K.M.Hastie et al. (2011). Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3' to 5' exonuclease activity essential for immune suppression. Proc Natl Acad Sci U S A, 108, 2396-2401. PubMed id: 21262835

Date:

04-Jan-11

Release date:

09-Feb-11

PROCHECK

	Headers

	References

Protein chain

P13699 (NCAP_LASSJ) - Nucleoprotein from Lassa virus (strain Mouse/Sierra Leone/Josiah/1976)

Seq: Struc:

Seq: Struc:					569 a.a. 209 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.3.1.13.- - ?????

[IntEnz] [ExPASy] [KEGG] [BRENDA]

	Proc Natl Acad Sci U S A 108:2396-2401 (2011)
PubMed id: 21262835

Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3' to 5' exonuclease activity essential for immune suppression.
K.M.Hastie, C.R.Kimberlin, M.A.Zandonatti, I.J.MacRae, E.O.Saphire.

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.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21482759

A.Martin, N.Hoefs, J.Tadewaldt, P.Staeheli, and U.Schneider (2011).
Genomic RNAs of Borna disease virus are elongated on internal template motifs after realignment of the 3' termini.

Proc Natl Acad Sci U S A, 108, 7206-7211.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.