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

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. © 2013 lu and gong.