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dc.contributor.authorWallat, Gregor D.
dc.contributor.authorHuang, Qinfeng
dc.contributor.authorWang, Wenjian
dc.contributor.authorDong, Haohao
dc.contributor.authorLy, Hinh
dc.contributor.authorLiang, Yuying
dc.contributor.authorDong, Changjiang
dc.identifier.citationWallat , G D , Huang , Q , Wang , W , Dong , H , Ly , H , Liang , Y & Dong , C 2014 , ' High-resolution structure of the n-terminal endonuclease domain of the lassa virus L polymerase in complex with magnesium ions ' , PLoS One , vol. 9 , no. 2 , e87577 .
dc.identifier.otherPURE: 116321306
dc.identifier.otherPURE UUID: 4b7be859-0757-4771-b4f2-6e0ad1c7a09a
dc.identifier.otherWOS: 000330834400015
dc.identifier.otherScopus: 84895518554
dc.identifier.otherWOS: 000330834400015
dc.descriptionThis work was supported in parts by the Wellcome trust fund (WT08351) and MRC (Medical Research Council) (G1100110/1) to CJD; NIH grants R01AI083409 to Y.L., and R56AI091805 and R01AI093580 to H.Len
dc.description.abstractLassa 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 angstrom. 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.
dc.relation.ispartofPLoS Oneen
dc.rights© 2014 Wallat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectRNA replicationen
dc.subjectFinger proteinen
dc.subjectPA subuniten
dc.subjectQR355 Virologyen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleHigh-resolution structure of the n-terminal endonuclease domain of the lassa virus L polymerase in complex with magnesium ionsen
dc.typeJournal articleen
dc.contributor.sponsorMedical Research Councilen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.description.statusPeer revieweden

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