The RNA-dependent RNA Polymerase 3D: Structure and Fidelity
Cristina Ferrer-Orta and Nuria Verdaguer
from: Foot-and-Mouth Disease Virus: Current Research and Emerging Trends (Edited by: Francisco Sobrino and Esteban Domingo). Caister Academic Press, U.K. (2017) Pages: 137-146.
RNA viruses typically encode their own RNA-dependent RNA polymerase (RdRP) to ensure genome replication within the infected cell. RdRP function is critical not only for the virus life cycle but also for its adaptive potential. The combination of low fidelity of replication and the absence of proofreading and excision activities within the RdRPs result in high mutation frequencies that allow these viruses for a rapid adaptation to changing environments. In this chapter, we summarize the current knowledge about structural and functional aspects on RdRP catalytic complexes, focused in the FMDV polymerase 3D. The RdRP 3D also catalyzes the covalent linkage of UMP to a tyrosine on the small protein VPg. Uridylylated VPg then serves as a protein primer for the initiation of RNA synthesis. Different crystal structures of FMDV 3D catalytic complexes enhanced our understanding of template and primer recognition, VPg uridylylation and rNTP binding and catalysis. Such structural information is providing new insights into the fidelity of RNA replication, and for the design of antiviral compounds read more ...