Rabies virus chaperone: identification of the phosphoprotein peptide that keeps nucleoprotein soluble and free from non-specific RNA

Virology. 2006 Jun 5;349(2):422-9. doi: 10.1016/j.virol.2006.01.030. Epub 2006 Feb 21.

Abstract

The genomic RNA of rabies virus is always complexed with the viral nucleoprotein (N). This N-RNA complex is the template for viral transcription and replication. The viral phosphoprotein (P) has two functions during the infection process: it binds through its carboxy-terminus to N in the N-RNA complex and at the same time with an amino-terminal domain to the polymerase and in this way fixes the polymerase to its template. The second function of P is to bind to newly produced N in the infected cell in order to prevent that N binds non-specifically and irreversibly to cellular RNA. In order to identify the part of the phosphoprotein that binds to N and keeps the latter soluble, we isolated the N-P complex, performed sequential protease digestions, and determined the identity of the remaining N and P peptides in the purified digested complex. Although the digestion steps removed short sequences of N, most of N remained intact and soluble, indicating that the overall structure was not affected. Most of P, including the carboxy-terminal N-RNA-binding domain, was removed during the first digestion step. N-terminal sequencing and mass spectrometry analysis identified a P peptide containing residues 4-40 that remained associated with N. Coexpression and coimmunoprecipitation experiments and yeast two-hybrid experiments showed that this peptide alone could bind to N in vivo.

MeSH terms

  • Amino Acid Sequence
  • Immunoprecipitation
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Nucleocapsid Proteins / chemistry
  • Nucleocapsid Proteins / metabolism*
  • Peptide Fragments / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Secondary
  • Rabies virus / genetics
  • Rabies virus / physiology*
  • Sequence Alignment
  • Trypsin / metabolism
  • Two-Hybrid System Techniques
  • Viral Structural Proteins / chemistry
  • Viral Structural Proteins / genetics
  • Viral Structural Proteins / metabolism*

Substances

  • Molecular Chaperones
  • Nucleocapsid Proteins
  • P phosphoprotein, Rabies virus
  • Peptide Fragments
  • Phosphoproteins
  • Viral Structural Proteins
  • nucleocapsid protein, Rabies virus
  • Trypsin