Structural highlights
Function
Q6GWS2_LASSJ RNA-dependent RNA polymerase, which is responsible for the replication and transcription of the viral RNA genome using antigenomic RNA as an intermediate. During transcription, synthesizes subgenomic RNAs and assures their capping by a cap-snatching mechanism, which involves the endonuclease activity cleaving the host capped pre-mRNAs. These short capped RNAs are then used as primers for viral transcription. The 3'-end of subgenomic mRNAs molecules are heterogeneous and not polyadenylated. The replicase function is to direct synthesis of antigenomic and genomic RNA which are encapsidated and non capped. As a consequence of the use of the same enzyme for both transcription and replication, these mechanisms need to be well coordinated. These processes may be regulated by proteins N and Z in a dose-dependent manner.[HAMAP-Rule:MF_04086][PIRNR:PIRNR000836]
Publication Abstract from PubMed
Lassa virus (LASV) causes deadly hemorrhagic fever disease for which there are no vaccines and limited treatments. LASV-encoded L polymerase is required for viral RNA replication and transcription. The functional domains of L-a large protein of 2218 amino acid residues-are largely undefined, except for the centrally located RNA-dependent RNA polymerase (RdRP) motif. Recent structural and functional analyses of the N-terminal region of the L protein from lymphocytic choriomeningitis virus (LCMV), which is in the same Arenaviridae family as LASV, have identified an endonuclease domain that presumably cleaves the cap structures of host mRNAs in order to initiate viral transcription. Here we present a high-resolution crystal structure of the N-terminal 173-aa region of the LASV L protein (LASV L173) in complex with magnesium ions at 1.72 A. The structure is highly homologous to other known viral endonucleases of arena- (LCMV NL1), orthomyxo- (influenza virus PA), and bunyaviruses (La Crosse virus NL1). Although the catalytic residues (D89, E102 and K122) are highly conserved among the known viral endonucleases, LASV L endonuclease structure shows some notable differences. Our data collected from in vitro endonuclease assays and a reporter-based LASV minigenome transcriptional assay in mammalian cells confirm structural prediction of LASV L173 as an active endonuclease. The high-resolution structure of the LASV L endonuclease domain in complex with magnesium ions should aid the development of antivirals against lethal Lassa hemorrhagic fever.
High-resolution structure of the N-terminal endonuclease domain of the lassa virus L polymerase in complex with magnesium ions.,Wallat GD, Huang Q, Wang W, Dong H, Ly H, Liang Y, Dong C PLoS One. 2014 Feb 7;9(2):e87577. doi: 10.1371/journal.pone.0087577. eCollection , 2014. PMID:24516554[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wallat GD, Huang Q, Wang W, Dong H, Ly H, Liang Y, Dong C. High-resolution structure of the N-terminal endonuclease domain of the lassa virus L polymerase in complex with magnesium ions. PLoS One. 2014 Feb 7;9(2):e87577. doi: 10.1371/journal.pone.0087577. eCollection , 2014. PMID:24516554 doi:http://dx.doi.org/10.1371/journal.pone.0087577
