Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface

• Published in: PLoS pathogens Vol. 9; no. 8; p. e1003549
• Main Authors: Lu, Guoliang, Gong, Peng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.08.2013; Public Library of Science (PLoS)
• Subjects: Amino Acid Motifs; Biology; Crystal structure; Crystallography, X-Ray; Crystals; Encephalitis; Encephalitis Virus, Japanese - enzymology; Encephalitis Virus, Japanese - genetics; Enzymes; Genomes; Health aspects; Host-parasite relationships; Methyltransferases; Methyltransferases - chemistry; Methyltransferases - genetics; Methyltransferases - metabolism; Molecular weight; Physiological aspects; Protein Structure, Tertiary; Proteins; Structure; Viral Nonstructural Proteins - chemistry; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - metabolism; Viruses; China
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003549

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.