title: Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family.
abstract: Interferon-lambda (IFN-lambda) is an antiviral cytokine that signals through a distinct receptor complex, composed of the IFN-lambdaR1 and interleukin-10R2 (IL-10R2) receptor chains. We have determined the crystal structure of human IFN-lambda3 and characterized the interaction with its receptor complex through structure-based site-directed mutagenesis. The ability of IFN-lambda3 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.
authors.affiliation: Centre for Structural Biology, Department of Molecular Biology, Aarhus University, Gustav, Wieds Vej 10, 8000 Arhus C, Denmark.
authors.forename: Hans Henrik
authors.initials: HH
authors.lastname: Gad
authors.forename: Christoffer
authors.initials: C
authors.lastname: Dellgren
authors.forename: Ole J
authors.initials: OJ
authors.lastname: Hamming
authors.forename: Susanne
authors.initials: S
authors.lastname: Vends
authors.forename: Søren R
authors.initials: SR
authors.lastname: Paludan
authors.forename: Rune
authors.initials: R
authors.lastname: Hartmann
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D007372:Interferons; D016753:Interleukin-10 / Q000737:chemistry*; D053710:Interleukin-10 Receptor beta Subunit / Q000378:metabolism; D007378:Interleukins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D050795:STAT2 Transcription Factor / Q000378:metabolism; D000097043:Interleukin-22; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D016753:Interleukin-10; D053710:Interleukin-10 Receptor beta Subunit; D007378:Interleukins; D050505:Mutant Proteins; D050795:STAT2 Transcription Factor; D000097043:Interleukin-22; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494084:STAT2 protein, human