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Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication

Zhao, Yongqian; Soh, Tingjin Sherryl; Chan, Kitti Wing Ki; Fung, Sarah Suet Yin; Swaminathan, Kunchithapadam; Lim, Siew Pheng; Shi, Pei-Yong; Lescar, Julien; Luo, Dahai; Vasudevan, Subhash; Huber, Thomas

Description

We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5’s conformational plasticity. Our biochemical and reverse genetics experiments demonstrate...[Show more]

dc.contributor.authorZhao, Yongqian
dc.contributor.authorSoh, Tingjin Sherryl
dc.contributor.authorChan, Kitti Wing Ki
dc.contributor.authorFung, Sarah Suet Yin
dc.contributor.authorSwaminathan, Kunchithapadam
dc.contributor.authorLim, Siew Pheng
dc.contributor.authorShi, Pei-Yong
dc.contributor.authorLescar, Julien
dc.contributor.authorLuo, Dahai
dc.contributor.authorVasudevan, Subhash
dc.contributor.authorHuber, Thomas
dc.date.accessioned2016-02-24T22:41:45Z
dc.identifier.issn0022-538X
dc.identifier.urihttp://hdl.handle.net/1885/98803
dc.description.abstractWe examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5’s conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication.
dc.publisherAmerican Society for Microbiology
dc.rightsAuthor/s retain copyright
dc.sourceJournal of Virology
dc.titleFlexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume89
dc.date.issued2015
local.identifier.absfor110000 - MEDICAL AND HEALTH SCIENCES
local.identifier.ariespublicationU3488905xPUB7628
local.type.statusPublished Version
local.contributor.affiliationZhao, Yongqian, National University of Singapore
local.contributor.affiliationSoh, Tingjin Sherryl, Nanyang Technological University
local.contributor.affiliationChan, Kitti Wing Ki, Duke-NUS Graduate Medical School
local.contributor.affiliationFung, Sarah Suet Yin, Duke-NUS Graduate Medical School
local.contributor.affiliationSwaminathan, Kunchithapadam, National University of Singapore
local.contributor.affiliationLim, Siew Pheng, Novartis Institute for Tropical Diseases
local.contributor.affiliationShi, Pei-Yong, Novartis Institute for Tropical Diseases
local.contributor.affiliationHuber, Thomas, College of Physical and Mathematical Sciences, ANU
local.contributor.affiliationLescar, Julien, Nanyang Technological University
local.contributor.affiliationLuo, Dahai, Nanyang Technological University
local.contributor.affiliationVasudevan, Subhash, Duke-NUS Graduate Medical School
local.bibliographicCitation.issue20
local.bibliographicCitation.startpage10717
local.bibliographicCitation.lastpage10721
local.identifier.doi10.1128/JVI.01239-15
dc.date.updated2016-02-24T10:14:54Z
local.identifier.scopusID2-s2.0-84942133731
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

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