Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family.
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.
Gad
Hans Henrik
HH
Centre for Structural Biology, Department of Molecular Biology, Aarhus University, Gustav, Wieds Vej 10, 8000 Arhus C, Denmark.
Dellgren
Christoffer
C
Hamming
Ole J
OJ
Vends
Susanne
S
Paludan
Søren R
SR
Hartmann
Rune
R
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
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