Overlap of interaction domains indicates a central role of the P protein in assembly and regulation of the Borna disease virus polymerase complex

J Biol Chem. 2004 Dec 31;279(53):55290-6. doi: 10.1074/jbc.M408913200. Epub 2004 Oct 27.

Abstract

The active polymerase complex of Borna disease virus is composed of the viral proteins N, P, and L. The viral X (negative regulatory factor) protein acts as a regulator of polymerase activity. Interactions of P with N and X were previously studied, but interactions with L were poorly defined. Using a mammalian two-hybrid system, we observed that L specifically interacts with P but not with N, X, or itself. Mapping of the L-binding domain in the P molecule revealed that it overlaps with two adjacent domains required for multimerization and interaction with N. Competition experiments showed that the interaction between L and P was inefficient when N was present, indicating that L may preferentially interact with free P in infected cells. Interestingly, a multimerization-defective P mutant maintained the ability to interact with L, N, and X but failed to support reporter gene expression from an artificial Borna disease virus minigenome. Furthermore, dominant negative effects on minigenome activity were only observed when P mutants with an intact multimerization domain were used, suggesting that P multimers, rather than monomers, exhibit biological activity. P mutants lacking functional interaction domains for L or N still formed complexes with these viral proteins when wild-type P was available as a bridging molecule, indicating that P multimers have the potential to act as scaffolds on which the RNA polymerase complex is assembled.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive
  • Borna disease virus / enzymology*
  • Cell Line
  • Chromatography, Gel
  • DNA, Complementary / metabolism
  • DNA-Directed RNA Polymerases / chemistry*
  • Genes, Dominant
  • Humans
  • Mutation
  • Phosphoproteins
  • Plasmids / metabolism
  • Point Mutation
  • Protein Binding
  • Protein Structure, Tertiary
  • Two-Hybrid System Techniques
  • Viral Proteins / chemistry*
  • Viral Structural Proteins / chemistry*
  • Viral Structural Proteins / physiology

Substances

  • DNA, Complementary
  • P protein, Borna disease virus
  • Phosphoproteins
  • Viral Proteins
  • Viral Structural Proteins
  • DNA-Directed RNA Polymerases