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Journal of Virology, June 2005, p. 7803-7811, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7803-7811.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Allosteric Effects of Ligands and Mutations on Poliovirus RNA-Dependent RNA Polymerase

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California,¹ Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine,² Department of Chemistry and Biochemistry, University of Colorado, Boulder Colorado³

Received 22 December 2003/ Accepted 29 January 2005

Protein priming of viral RNA synthesis plays an essential role in the replication of picornavirus RNA. Both poliovirus and coxsackievirus encode a small polypeptide, VPg, which serves as a primer for addition of the first nucleotide during synthesis of both positive and negative strands. This study examined the effects on the VPg uridylylation reaction of the RNA template sequence, the origin of VPg (coxsackievirus or poliovirus), the origin of 3D polymerase (coxsackievirus or poliovirus), the presence and origin of interacting protein 3CD, and the introduction of mutations at specific regions in the poliovirus 3D polymerase. Substantial effects associated with VPg origin were traced to differences in VPg-polymerase interactions. The effects of 3CD proteins and mutations at polymerase-polymerase intermolecular Interface I were most consistent with allosteric effects on the catalytic 3D polymerase molecule. In conclusion, the efficiency and specificity of VPg uridylylation by picornavirus polymerases is greatly influenced by allosteric effects of ligand binding that are likely to be relevant during the viral replicative cycle.

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