Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication

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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Bibliographic Details
Main Authors: 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.
Other Authors: Diamond, M. S.
Format: Article
Language:English
Published: 2015
Online Access:https://hdl.handle.net/10356/103841
http://hdl.handle.net/10220/38795
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Institution: Nanyang Technological University
Language: English
Description
Summary: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.

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