Structural basis of a unique interferon-β signaling axis mediated via the receptor IFNAR1

Nat Immunol. 2013 Sep;14(9):901-7. doi: 10.1038/ni.2667. Epub 2013 Jul 21.


Type I interferons are important in regulating immune responses to pathogens and tumors. All interferons are considered to signal via the heterodimeric IFNAR1-IFNAR2 complex, yet some subtypes such as interferon-β (IFN-β) can exhibit distinct functional properties, although the molecular basis of this is unclear. Here we demonstrate IFN-β can uniquely and specifically ligate to IFNAR1 in an IFNAR2-independent manner, and we provide the structural basis of the IFNAR1-IFN-β interaction. The IFNAR1-IFN-β complex transduced signals that modulated expression of a distinct set of genes independently of Jak-STAT pathways. Lipopolysaccharide-induced sepsis was ameliorated in Ifnar1(-/-) mice but not Ifnar2(-/-) mice, suggesting that IFNAR1-IFN-β signaling is pathologically relevant. Thus, we provide a molecular basis for understanding specific functions of IFN-β.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Interferon-beta / chemistry*
  • Interferon-beta / metabolism*
  • Lipopolysaccharides / adverse effects
  • Mice
  • Mice, Knockout
  • Models, Molecular
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Stability
  • Receptor, Interferon alpha-beta / chemistry*
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism*
  • Shock, Septic / chemically induced
  • Shock, Septic / genetics
  • Shock, Septic / metabolism
  • Shock, Septic / mortality
  • Signal Transduction*


  • Lipopolysaccharides
  • Multiprotein Complexes
  • Receptor, Interferon alpha-beta
  • Interferon-beta