Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication
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...
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sg-ntu-dr.10356-1038412022-02-16T16:29:06Z 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 Huber, Thomas Lescar, Julien Luo, Dahai Vasudevan, Subhash G. Diamond, M. S. Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences 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 that NS5 utilizes conformational regulation to achieve optimum viral replication. Published version 2015-10-13T02:49:30Z 2019-12-06T21:21:27Z 2015-10-13T02:49:30Z 2019-12-06T21:21:27Z 2015 2015 Journal Article Zhao, Y., Soh, T. S., Chan, K. W. K., Fung, S. S. Y., Swaminathan, K., Lim, S. P., et al. (2015). Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication. Journal of Virology, 89(20), 10717-10721. https://hdl.handle.net/10356/103841 http://hdl.handle.net/10220/38795 10.1128/JVI.01239-15 26269182 en Journal of Virology © 2015 American Society for Microbiology. This paper was published in Journal of Virology and is made available as an electronic reprint (preprint) with permission of American Society for Microbiology. The published version is available at: [http://dx.doi.org/10.1128/JVI.01239-15]. 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. application/pdf |
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| 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 that NS5 utilizes conformational regulation to achieve optimum viral replication. |
| author2 |
Diamond, M. S. |
| author_facet |
Diamond, M. S. Zhao, Yongqian Soh, Tingjin Sherryl Chan, Kitti Wing Ki Fung, Sarah Suet Yin Swaminathan, Kunchithapadam Lim, Siew Pheng Shi, Pei-Yong Huber, Thomas Lescar, Julien Luo, Dahai Vasudevan, Subhash G. |
| format |
Article |
| author |
Zhao, Yongqian Soh, Tingjin Sherryl Chan, Kitti Wing Ki Fung, Sarah Suet Yin Swaminathan, Kunchithapadam Lim, Siew Pheng Shi, Pei-Yong Huber, Thomas Lescar, Julien Luo, Dahai Vasudevan, Subhash G. |
| spellingShingle |
Zhao, Yongqian Soh, Tingjin Sherryl Chan, Kitti Wing Ki Fung, Sarah Suet Yin Swaminathan, Kunchithapadam Lim, Siew Pheng Shi, Pei-Yong Huber, Thomas Lescar, Julien Luo, Dahai Vasudevan, Subhash G. Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication |
| author_sort |
Zhao, Yongqian |
| title |
Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication |
| title_short |
Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication |
| title_full |
Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication |
| title_fullStr |
Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication |
| title_full_unstemmed |
Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication |
| title_sort |
flexibility of ns5 methyltransferase-polymerase linker region is essential for dengue virus replication |
| publishDate |
2015 |
| url |
https://hdl.handle.net/10356/103841 http://hdl.handle.net/10220/38795 |
| _version_ |
1725985707826085888 |