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
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]
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|Source:||Journal of Virology|
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