The interface between methyltransferase and polymerase of NS5 is essential for flavivirus replication

The flavivirus NS5 harbors both a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP). Both enzyme activities of NS5 are critical for viral replication. Recently, the full-length NS5 crystal structure of Japanese encephalitis virus reveals a conserved MTase-RdRP interface that featu...

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Bibliographic Details
Published in:PLoS neglected tropical diseases 2014-05, Vol.8 (5), p.e2891
Main Authors: Li, Xiao-Dan, Shan, Chao, Deng, Cheng-Lin, Ye, Han-Qing, Shi, Pei-Yong, Yuan, Zhi-Ming, Gong, Peng, Zhang, Bo
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Biology and life sciences
Cell Line
Conserved Sequence
Crystal structure
Dengue fever
Dengue virus
DNA-Directed RNA Polymerases - chemistry
DNA-Directed RNA Polymerases - genetics
Encephalitis
Flavivirus
Flavivirus - genetics
Flavivirus - physiology
Hydrophobic and Hydrophilic Interactions
Japanese encephalitis virus
Medicine and Health Sciences
Methyltransferases
Methyltransferases - chemistry
Methyltransferases - genetics
Molecular Sequence Data
Mutation
Properties
RNA polymerases
Sequence Alignment
Viral infections
Viral Nonstructural Proteins - chemistry
Viral Nonstructural Proteins - genetics
Virus Replication - genetics
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Description
Summary:The flavivirus NS5 harbors both a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP). Both enzyme activities of NS5 are critical for viral replication. Recently, the full-length NS5 crystal structure of Japanese encephalitis virus reveals a conserved MTase-RdRP interface that features two conserved components: a six-residue hydrophobic network and a GTR sequence. Here we showed for the first time that these key interface components are essential for flavivirus replication by various reverse genetics approaches. Interestingly, some replication-impaired variants generated a common compensatory NS5 mutation outside the interface (L322F), providing novel routes to further explore the crosstalk between MTase and RdRP.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0002891