Structural properties of the human respiratory syncytial virus P protein: evidence for an elongated homotetrameric molecule that is the smallest orthologue within the family of paramyxovirus polymerase cofactors

Proteins. 2008 Aug 15;72(3):946-58. doi: 10.1002/prot.21988.

Abstract

The oligomeric state and the hydrodynamic properties of human respiratory syncytial virus (HRSV) phosphoprotein (P), a known cofactor of the viral RNA-dependent RNA polymerase (L), and a trypsin-resistant fragment (X) that includes its oligomerization domain were analyzed by sedimentation equilibrium and velocity using analytical ultracentrifugation. The results obtained demonstrate that both P and fragment X are homotetrameric with elongated shapes, consistent with electron micrographs of the purified P protein in which thin rod-like molecules of approximately 12.5 +/- 1.0 nm in length were observed. A new chymotrypsin resistant fragment (Y*) included in fragment X has been identified and purified by gel filtration chromatography. Fragment Y* may represent a minimal version of the P oligomerization domain. Thermal denaturation curves based on circular dichroism data of P protein showed a complex behavior. In contrast, melting data generated for fragments X and particularly fragment Y* showed more homogeneous transitions indicative of simpler structures. A three-dimensional model of X and Y* fragments was built based on the atomic structure of the P oligomerization domain of the related Sendai virus, which is in good agreement with the experimental data. This model will be an useful tool to make rational mutations and test the role of specific amino acids in the oligomerization and functional properties of the HRSV P protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Chymotrypsin
  • Circular Dichroism
  • Coenzymes / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Protein Denaturation
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • RNA-Dependent RNA Polymerase / metabolism*
  • Respiratory Syncytial Virus, Human / enzymology*
  • Sequence Homology, Amino Acid*
  • Temperature
  • Thermodynamics
  • Trypsin
  • Viral Structural Proteins / chemistry*
  • Viral Structural Proteins / ultrastructure

Substances

  • Coenzymes
  • P protein, human respiratory syncytial virus
  • Peptide Fragments
  • Viral Structural Proteins
  • RNA-Dependent RNA Polymerase
  • Chymotrypsin
  • Trypsin