Structure of the vesicular stomatitis virus nucleocapsid in complex with the nucleocapsid-binding domain of the small polymerase cofactor, P

Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11713-8. doi: 10.1073/pnas.0903228106. Epub 2009 Jul 1.

Abstract

The negative-strand RNA viruses (NSRVs) are unique because their nucleocapsid, not the naked RNA, is the active template for transcription and replication. The viral polymerase of nonsegmented NSRVs contains a large polymerase catalytic subunit (L) and a nonenzymatic cofactor, the phosphoprotein (P). Insight into how P delivers the polymerase complex to the nucleocapsid has long been pursued by reverse genetics and biochemical approaches. Here, we present the X-ray crystal structure of the C-terminal domain of P of vesicular stomatitis virus, a prototypic nonsegmented NSRV, bound to nucleocapsid-like particles. P binds primarily to the C-terminal lobe of 2 adjacent N proteins within the nucleocapsid. This binding mode is exclusive to the nucleocapsid, not the nucleocapsid (N) protein in other existing forms. Localization of phosphorylation sites within P and their proximity to the RNA cavity give insight into how the L protein might be oriented to access the RNA template.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Crystallography, X-Ray
  • DNA-Directed RNA Polymerases / metabolism*
  • Models, Molecular*
  • Nucleocapsid / chemistry*
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Conformation
  • Vesicular stomatitis Indiana virus / chemistry*

Substances

  • Phosphoproteins
  • DNA-Directed RNA Polymerases

Associated data

  • PDB/3HHW
  • PDB/3HHZ