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4MIW

High-resolution structure of the N-terminal endonuclease domain of the Lassa virus L polymerase

Summary for 4MIW
Entry DOI10.2210/pdb4miw/pdb
DescriptorRNA-directed RNA polymerase L, MAGNESIUM ION (3 entities in total)
Functional Keywordsbeta sheet, helix, endoribonuclease type ii, endonuclease, viral protein, transferase
Biological sourceLassa virus
Total number of polymer chains1
Total formula weight20359.98
Authors
Wallat, G.D.,Huang, Q.,Wang, W.,Dong, H.,Ly, H.,Liang, Y.,Dong, C. (deposition date: 2013-09-02, release date: 2014-03-19, Last modification date: 2023-09-20)
Primary citationWallat, G.D.,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, 9:e87577-e87577, 2014
Cited by
PubMed Abstract: 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 Å. 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.
PubMed: 24516554
DOI: 10.1371/journal.pone.0087577
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.72 Å)
Structure validation

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