dc.contributor.authorHew, Kelly
dc.contributor.authorVeerappan, Saranya
dc.contributor.authorSim, Daniel
dc.contributor.authorCornvik, Tobias
dc.contributor.authorNordlund, Pär
dc.contributor.authorDahlroth, Sue-Li
dc.contributor.editorJung, Jae U.*
dc.date.accessioned2017-02-03T06:49:03Z
dc.date.available2017-02-03T06:49:03Z
dc.date.issued2017
dc.identifier.citationHew, K., Veerappan, S., Sim, D., Cornvik, T., Nordlund, P., & Dahlroth, S.-L. (2017). Structure of the Open Reading Frame 49 Protein Encoded by Kaposi's Sarcoma-Associated Herpesvirus. Journal of Virology, 91(2), e01947-16-.en_US
dc.identifier.issn0022-538Xen_US
dc.identifier.urihttp://hdl.handle.net/10220/42068
dc.description.abstractHerpesviruses alternate between the latent and the lytic life cycle. Switching into the lytic life cycle is important for herpesviral replication and disease pathogenesis. Activation of a transcription factor replication and transcription activator (RTA) has been demonstrated to govern this switch in Kaposi's sarcoma-associated herpesvirus (KSHV). The protein encoded by open reading frame 49 from KSHV (ORF49KSHV) has been shown to upregulate lytic replication in KSHV by enhancing the activities of the RTA. We have solved the crystal structure of the ORF49KSHV protein to a resolution of 2.4 Å. The ORF49KSHV protein has a novel fold consisting of 12 alpha-helices bundled into two pseudodomains. Most notably are distinct charged patches on the protein surface, which are possible protein-protein interaction sites. Homologs of the ORF49KSHV protein in the gammaherpesvirus subfamily have low sequence similarities. Conserved residues are mainly located in the hydrophobic regions, suggesting that they are more likely to play important structural roles than functional ones. Based on the identification and position of three sulfates binding to the positive areas, we performed some initial protein-DNA binding studies by analyzing the thermal stabilization of the protein in the presence of DNA. The ORF49KSHV protein is stabilized in a dose-responsive manner by double-stranded oligonucleotides, suggesting actual DNA interaction and binding. Biolayer interferometry studies also demonstrated that the ORF49KSHV protein binds these oligonucleotides.en_US
dc.description.sponsorshipASTAR (Agency for Sci., Tech. and Research, S’pore)en_US
dc.format.extent11 p.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesJournal of Virologyen_US
dc.rights© 2017 American Society for Microbiology (ASM). This paper was published in Journal of Virology and is made available as an electronic reprint (preprint) with permission of American Society for Microbiology (ASM). The published version is available at: [http://dx.doi.org/10.1128/JVI.01947-16]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.en_US
dc.subjectHerpesvirusen_US
dc.subjectKaposi's sarcoma-associated herpesvirusen_US
dc.titleStructure of the Open Reading Frame 49 Protein Encoded by Kaposi Sarcoma-Associated Herpesvirusen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.identifier.doihttp://dx.doi.org/10.1128/JVI.01947-16
dc.description.versionPublished versionen_US


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