High-resolution structure of the N-terminal endonuclease domain of the Lassa virus L polymerase in complex with magnesium ions.
High-resolution structure of the N-terminal endonuclease domain of the Lassa virus L polymerase in complex with magnesium ions.
复制标题
DOI：
10.1371/journal.pone.0087577
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Dong C
中科院分区：
文献类型：
--
作者：
Wallat GD;Huang Q;Wang W;Dong H;Ly H;Liang Y;Dong C
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.
登录
查看更多内容
DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
影响因子：
6.7
作者：
Morin B;Coutard B;Lelke M;Ferron F;Kerber R;Jamal S;Frangeul A;Baronti C;Charrel R;de Lamballerie X;Vonrhein C;Lescar J;Bricogne G;Günther S;Canard B
通讯作者：
Canard B
影响因子：
11.8
作者：
Amorosa, Valerianna;MacNeil, Adam;Nichol, Stuart T.
通讯作者：
Nichol, Stuart T.
影响因子：
158.5
作者：
MCCORMICK, JB;KING, IJ;BELMONTWILLIAMS, R
通讯作者：
BELMONTWILLIAMS, R
DOI：
10.1073/pnas.221447598
发表时间：
2001-10-23
影响因子：
11.1
作者：
Lenz, O;ter Meulen, J;Garten, W
通讯作者：
Garten, W