Structural and biophysical characterization of the Borna disease virus 1 phosphoprotein

Acta Crystallogr F Struct Biol Commun. 2023 Mar 1;79(Pt 3):51-60. doi: 10.1107/S2053230X23000717. Epub 2023 Feb 23.

Abstract

Bornaviruses are RNA viruses with a mammalian, reptilian, and avian host range. The viruses infect neuronal cells and in rare cases cause a lethal encephalitis. The family Bornaviridae are part of the Mononegavirales order of viruses, which contain a nonsegmented viral genome. Mononegavirales encode a viral phosphoprotein (P) that binds both the viral polymerase (L) and the viral nucleoprotein (N). The P protein acts as a molecular chaperone and is required for the formation of a functional replication/transcription complex. In this study, the structure of the oligomerization domain of the phosphoprotein determined by X-ray crystallography is reported. The structural results are complemented with biophysical characterization using circular dichroism, differential scanning calorimetry and small-angle X-ray scattering. The data reveal the phosphoprotein to assemble into a stable tetramer, with the regions outside the oligomerization domain remaining highly flexible. A helix-breaking motif is observed between the α-helices at the midpoint of the oligomerization domain that appears to be conserved across the Bornaviridae. These data provide information on an important component of the bornavirus replication complex.

Keywords: X-ray crystallography; bornavirus; negative-strand RNA viruses; phosphoproteins; replication.

MeSH terms

  • Animals
  • Borna disease virus* / genetics
  • Calorimetry, Differential Scanning
  • Circular Dichroism
  • Crystallography, X-Ray
  • Mammals
  • Nucleoproteins
  • Phosphoproteins / metabolism

Substances

  • Nucleoproteins
  • Phosphoproteins