ABSTRACT
In the replication cycle of nonsegmented negative-strand RNA viruses, the viral RNA-dependent RNA polymerase (L) recognizes a nucleoprotein (N)-enwrapped RNA template during the RNA polymerase reaction. The viral phosphoprotein (P) is a polymerase cofactor essential for this recognition. We report here the 2.3-Å-resolution crystal structure of the central domain (residues 107 to 177) of P from vesicular stomatitis virus. The fold of this domain consists of a β hairpin, an α helix, and another β hairpin. The α helix provides the stabilizing force for forming a homodimer, while the two β hairpins add additional stabilization by forming a four-stranded β sheet through domain swapping between two molecules. This central dimer positions the N- and C-terminal domains of P to interact with the N and L proteins, allowing the L protein to specifically recognize the nucleocapsid-RNA template and to progress along the template while concomitantly assembling N with nascent RNA. The interdimer interactions observed in the noncrystallographic packing may offer insight into the mechanism of the RNA polymerase processive reaction along the viral nucleocapsid-RNA template.
Sequence-specific contacts between the RNA polymerase of vesicular stomatitis virus and the leader RNA gene.
