4MIW

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

4MIW の概要

• エントリーDOI: 10.2210/pdb4miw/pdb
• 分子名称: RNA-directed RNA polymerase L, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: beta sheet, helix, endoribonuclease type ii, endonuclease, viral protein, transferase
• 由来する生物種: Lassa virus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20359.98

構造登録者

Wallat, G.D.,Huang, Q.,Wang, W.,Dong, H.,Ly, H.,Liang, Y.,Dong, C. (登録日: 2013-09-02, 公開日: 2014-03-19, 最終更新日: 2023-09-20)

主引用文献

Wallat, 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

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

実験手法

X-RAY DIFFRACTION (1.72 Å)