Structure and Function of the Flavivirus NS5 Protein
Julien Lescar, Siew Pheng Lim and Pei-Yong Shi
from: Molecular Virology and Control of Flaviviruses (Edited by: Pei-Yong Shi). Caister Academic Press, U.K. (2012)
Abstract
The non-structural protein 5 (NS5) of flaviviruses is the most conserved amongst the viral proteins. It is about 900 kDa and bears several enzymatic activities that play vital roles in virus replication. Its N-terminal domain encodes dual N7 and 2'-O methyltransferase activities (MTase), and possibly guanylyltransferase (GTase) involved in RNA cap formation. The C-terminal region comprises a RNA-dependent RNA polymerase (RdRp) required for viral RNA synthesis. Numerous crystal structures of the Flavivirus MTase and RdRp domains have been solved. MTase in complex with S-adenosyl homocysteine (SAHC) or GTP analogues showed that the domain adopts a classical 2'-O MTase fold, however, the mechanism by which the protein can perform N7-methylation is still unknown. Besides its critical enzymatic activities, NS5 has also been implicated in viral pathogenesis through phosphorylation by host cell kinases, nucleus trafficking, and interference with interferon signalling and cytokine production. Here we summarize recent progress on this highly intriguing protein read more ...
