Interferon-λ Is Functionally an Interferon but Structurally Related to the Interleukin-10 Family

被引：162

作者：

Gad, Hans Henrik ^{[1
]}

Dellgren, Christoffer ^{[1
]}

Hamming, Ole J. ^{[1
]}

Vends, Susanne ^{[1
]}

Paludan, Soren R. ^{[2
]}

Hartmann, Rune ^{[1
]}

机构：

[1] Aarhus Univ, Dept Mol Biol, Struct Biol Ctr, DK-8000 Aarhus C, Denmark

[2] Aarhus Univ, Dept Med Microbiol & Immunol, DK-8000 Aarhus C, Denmark

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 31期

基金：

英国医学研究理事会;

关键词：

IFN-LAMBDA; CRYSTAL-STRUCTURE; IL-10R2; BINDING; HOST-DEFENSE; III IFN; IL-22; CRYSTALLOGRAPHY; CYTOKINES; SOFTWARE; COMPLEX;

D O I：

10.1074/jbc.M109.002923

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Interferon-lambda (IFN-lambda) is an antiviral cytokine that signals through a distinct receptor complex, composed of the IFN-lambda R1 and interleukin-10R2 (IL-10R2) receptor chains. We have determined the crystal structure of human IFN-lambda 3 and characterized the interaction with its receptor complex through structure-based site-directed mutagenesis. The ability of IFN-lambda 3 mutants to signal was determined by measuring the antiviral activity and induced STAT2 phosphorylation. In conclusion, our data show that, although IFN-lambda is functionally an interferon, it is clearly structurally related to members of the IL-10 family. In particular, we found an interesting similarity between IFN-lambda and IL-22, and we suggest that IFN-lambda and IL-22 possess parallel functions, protecting epithelial tissue against viral and bacterial infections, respectively.

引用

页码：20869 / 20875

页数：7

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