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Journal of Virology, March 2006, p. 2808-2814, Vol. 80, No. 6
0022-538X/06/$08.00+0 doi:10.1128/JVI.80.6.2808-2814.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Department of Microbiology, School of Medicine, University of Alabama at Birmingham, 1025 18th Street South, Birmingham, Alabama 35294
Received 29 September 2005/ Accepted 13 December 2005
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 ß hairpin, an
helix, and another ß hairpin. The
helix provides the stabilizing force for forming a homodimer, while the two ß hairpins add additional stabilization by forming a four-stranded ß 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.
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