Sequence specificity for uridylylation of the viral peptide linked to the genome (VPg) of enteroviruses.

Schein CH1, Ye M2, Paul AV3, Oberste MS4, Chapman N5, van der Heden van Noort GJ6, Filippov DV6, Choi K2.

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Abstract

Enteroviruses (EV) uridylylate a peptide, VPg, as the first step in their replication. VPgpUpU, found free in infected cells, serves as the primer for RNA elongation. The abilities of four polymerases (3Dpol), from EV-species A-C, to uridylylate VPgs that varied by up to 60% of their residues were compared. Each 3Dpol was able to uridylylate all five VPgs using polyA RNA as template, while showing specificity for its own genome encoded peptide. All 3Dpol uridylylated a consensus VPg representing the physical chemical properties of 31 different VPgs. Thus the residues required for uridylylation and the enzymatic mechanism must be similar in diverse EV. As VPg-binding sites differ in co-crystal structures, the reaction is probably done by a second 3Dpol molecule. The conservation of polymerase residues whose mutation reduces uridylylation but not RNA elongation is compared.

KEYWORDS:

Coxsackie virus; EV-71; Metal ion dependent phosphotransfer; Nucleotide transfer reaction; PCP-consensus sequence; Peptide priming; Poliovirus; RNA polymerase