New Insights into Structural Disorder in Human Respiratory Syncytial Virus Phosphoprotein and Implications for Binding of Protein Partners

J Biol Chem. 2017 Feb 10;292(6):2120-2131. doi: 10.1074/jbc.M116.765958. Epub 2016 Dec 28.

Abstract

Phosphoprotein is the main cofactor of the viral RNA polymerase of Mononegavirales It is involved in multiple interactions that are essential for the polymerase function. Most prominently it positions the polymerase complex onto the nucleocapsid, but also acts as a chaperone for the nucleoprotein. Mononegavirales phosphoproteins lack sequence conservation, but contain all large disordered regions. We show here that N- and C-terminal intrinsically disordered regions account for 80% of the phosphoprotein of the respiratory syncytial virus. But these regions display marked dynamic heterogeneity. Whereas almost stable helices are formed C terminally to the oligomerization domain, extremely transient helices are present in the N-terminal region. They all mediate internal long-range contacts in this non-globular protein. Transient secondary elements together with fully disordered regions also provide protein binding sites recognized by the respiratory syncytial virus nucleoprotein and compatible with weak interactions required for the processivity of the polymerase.

Keywords: RNA dependent RNA polymerase; intrinsically disordered protein; molecular recognition element; nuclear magnetic resonance (NMR); nucleoprotein; phosphoprotein; protein dynamic; respiratory syncytial virus; viral replication; viral transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Electron Spin Resonance Spectroscopy
  • Intrinsically Disordered Proteins / chemistry
  • Intrinsically Disordered Proteins / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • Respiratory Syncytial Virus, Human / metabolism*
  • Sequence Homology, Amino Acid

Substances

  • Intrinsically Disordered Proteins
  • Phosphoproteins

Associated data

  • PDB/2WJ8
  • PDB/5FVD
  • PDB/4BXT