Poliovirus RNA-Dependent RNA Polymerase (3Dpol): Structure, Function, and Mechanism

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Abstract
Replication of the poliovirus genome has been studied for many decades by using a variety of molecular, genetic, biochemical, and structural approaches. These studies have uncovered most, if not all, of the virus encoded proteins and RNA sequences/structures required for genome replication. Proteins encoded by the P3 region of the genome, however, are thought to participate more directly in the genome replication process. The fourth and final protein domain of the P3 region of the viral polyprotein is the RNA-dependent RNA polymerase (RdRP) 3Dpol, the core component of the replication machinery. One of the most important contributions to one’s understanding of 3Dpol function was the solution of the crystal structure of 3Dpol by researchers in 1997. This structure provided the first glimpse into the architecture of an RdRP. The preceding discussion highlights the similarity of 3Dpol with other classes of nucleic acid polymerase. While features unique to 3Dpol may exist, for example, the so-called fingertips, this subdomain likely exists in all RdRPs based on the two RdRP structures available to date. In contrast, two potential interaction/oligomerization domains were also observed in the crystal structure of 3Dpol. These interaction surfaces have no structural homologues in any other polymerases for which structural information is available, including the RdRP from hepatitis C virus (HCV). It is clear that the availability of structural information for 3Dpol has shed light on one’s understanding of 3Dpol function.