Interferon-λ Is Functionally an Interferon but Structurally Related to the Interleukin-10 Family
Interferon-λ Is Functionally an Interferon but Structurally Related to the Interleukin-10 Family
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DOI：
10.1074/jbc.m109.002923
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发表时间：
2009-07-31
影响因子：
4.8
通讯作者：
Hartmann, Rune
中科院分区：
文献类型：
--
作者：
Gad, Hans Henrik;Dellgren, Christoffer;Hartmann, Rune
干扰素-λ（IFN-λ）是一种抗病毒细胞因子，其通过由IFN-λ R1和白细胞介素-10R2（IL-10 R2）受体链组成的不同受体复合物发出信号。我们已经确定了人IFN-λ 3的晶体结构，并通过基于结构的定点突变表征了与其受体复合物的相互作用。通过测量抗病毒活性和诱导的STAT 2磷酸化来确定IFN-λ 3突变体的信号传导能力。总之，我们的数据表明，虽然IFN-λ在功能上是一种干扰素，但它在结构上与IL-10家族成员明显相关。特别是，我们发现了一个有趣的相似性之间的IFN-λ和IL-22，我们认为，IFN-λ和IL-22具有平行的功能，分别保护上皮组织免受病毒和细菌感染。
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.