西亞試劑：Structural basis of a unique interferon-β signaling axis me

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

Nicole A de Weerd, Julian P Vivian, Thao K Nguyen, Niamh E Mangan, Jodee A Gould, Susie-Jane Braniff, Leyla Zaker-Tabrizi, Ka Yee Fung, Samuel C Forster,Travis Beddoe,Hugh H Reid,Jamie Rossjohn & Paul J Hertzog

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.

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