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

Nicole Anne De Weerd; Julian Vivian; Thao K Nguyen; Niamh Mangan; Jodee Ann Gould; Susie-Jane Braniff; Leyla Zaker-Tabrizi; Ka Yee Fung; Samuel Forster; Travis Clarke Beddoe; Hugh Harrington Reid; Jamie Rossjohn; Paul John Hertzog

doi:10.1038/ni.2667

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

Nicole Anne De Weerd, Julian Vivian, Thao K Nguyen, Niamh Mangan, Jodee Ann Gould, Susie-Jane Braniff, Leyla Zaker-Tabrizi, Ka Yee Fung, Samuel Forster, Travis Clarke Beddoe, Hugh Harrington Reid, Jamie Rossjohn, Paul John Hertzog

Research output: Contribution to journal › Article › Research › peer-review

167 Citations (Scopus)

Abstract

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-beta (IFN-beta) can exhibit distinct functional properties, although the molecular basis of this is unclear. Here we demonstrate IFN-beta can uniquely and specifically ligate to IFNAR1 in an IFNAR2-independent manner, and we provide the structural basis of the IFNAR1-IFN-beta interaction. The IFNAR1-IFN-beta 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-beta signaling is pathologically relevant. Thus, we provide a molecular basis for understanding specific functions of IFN-beta.

Original language	English
Pages (from-to)	901 - 907
Number of pages	7
Journal	Nature Immunology
Volume	14
Issue number	9
DOIs	https://doi.org/10.1038/ni.2667
Publication status	Published - 2013

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De Weerd, Nicole Anne ; Vivian, Julian ; Nguyen, Thao K ; Mangan, Niamh ; Gould, Jodee Ann ; Braniff, Susie-Jane ; Zaker-Tabrizi, Leyla ; Fung, Ka Yee ; Forster, Samuel ; Beddoe, Travis Clarke ; Reid, Hugh Harrington ; Rossjohn, Jamie ; Hertzog, Paul John. / Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1. In: Nature Immunology. 2013 ; Vol. 14, No. 9. pp. 901 - 907.

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abstract = "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-beta (IFN-beta) can exhibit distinct functional properties, although the molecular basis of this is unclear. Here we demonstrate IFN-beta can uniquely and specifically ligate to IFNAR1 in an IFNAR2-independent manner, and we provide the structural basis of the IFNAR1-IFN-beta interaction. The IFNAR1-IFN-beta 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-beta signaling is pathologically relevant. Thus, we provide a molecular basis for understanding specific functions of IFN-beta.",

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Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1. / De Weerd, Nicole Anne ; Vivian, Julian; Nguyen, Thao K; Mangan, Niamh; Gould, Jodee Ann; Braniff, Susie-Jane; Zaker-Tabrizi, Leyla; Fung, Ka Yee; Forster, Samuel ; Beddoe, Travis Clarke ; Reid, Hugh Harrington ; Rossjohn, Jamie ; Hertzog, Paul John.

In: Nature Immunology, Vol. 14, No. 9, 2013, p. 901 - 907.

Research output: Contribution to journal › Article › Research › peer-review

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AU - Braniff, Susie-Jane

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AU - Beddoe, Travis Clarke

AU - Reid, Hugh Harrington

AU - Rossjohn, Jamie

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