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

被引：214

作者：

de Weerd, Nicole A. ^{[1
,2
]}

Vivian, Julian P. ^{[3
]}

Nguyen, Thao K. ^{[1
,2
,3
]}

Mangan, Niamh E. ^{[1
]}

Gould, Jodee A. ^{[1
,2
]}

Braniff, Susie-Jane ^{[1
]}

Zaker-Tabrizi, Leyla ^{[1
]}

Fung, Ka Yee ^{[1
]}

Forster, Samuel C. ^{[1
,2
]}

Beddoe, Travis ^{[3
]}

Reid, Hugh H. ^{[3
]}

Rossjohn, Jamie ^{[2
,3
,4
]}

Hertzog, Paul J. ^{[1
,2
]}

机构：

[1] Monash Univ, Monash Inst Med Res, Ctr Innate Immun & Infect Dis, Clayton, Vic, Australia

[2] Monash Univ, Australian Res Council Ctr Excellence Struct & Fu, Clayton, Vic, Australia

[3] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic, Australia

[4] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 09期

基金：

澳大利亚国家健康与医学研究理事会; 澳大利亚研究理事会; 英国医学研究理事会;

关键词：

I INTERFERONS; ALPHA; LIPOPOLYSACCHARIDE; INDUCTION; RESPONSES; SUBUNIT; ACTIVATION; REFINEMENT; SUPPRESSOR;

D O I：

10.1038/ni.2667

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：901 / +

页数：9

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