Crystal Structure of the Full-Length Japanese Encephalitis Virus NS5 Reveals a Conserved Methyltransferase-Polymerase Interface

PLoS Pathogens

Guoliang Lu¹  Peng Gong² 

[1] State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuchang District, Wuhan, Hubei, China;University of Chinese Academy of Sciences, Beijing, China

关键词: Crystal structure;    Polymerases;    Viral structure;    Flaviviruses;    West Nile virus;    Thumbs;    Protein structure;    RNA synthesis;   

DOI  :  10.1371/journal.ppat.1003549

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.

【 授权许可】

CC BY