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PMID: 19457860 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family.

The Journal of biological chemistry ·Vol. 284 ·No. 31 ·2009-07-31 ·Pages 20869-75

Gad HH, Dellgren C, Hamming OJ, Vends S, Paludan SR, Hartmann R

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.

MeSH Terms
Antiviral Agents/metabolism Binding Sites Cell Line, Tumor Crystallography, X-Ray Humans Interferons Interleukin-10/chemistry Interleukin-10 Receptor beta Subunit/metabolism Interleukins/chemistry,metabolism Models, Molecular Mutant Proteins/chemistry,metabolism Phosphorylation Protein Binding Protein Structure, Secondary STAT2 Transcription Factor/metabolism
Chemicals
Antiviral Agents IFNL3 protein, human Interleukin-10 Receptor beta Subunit Interleukins Mutant Proteins STAT2 Transcription Factor STAT2 protein, human Interleukin-10 Interferons interleukin-22
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Gad Hans Henrik
Centre for Structural Biology, Department of Molecular Biology, Aarhus University, Gustav, Wieds Vej 10, 8000 Arhus C, Denmark.
Dellgren Christoffer
Hamming Ole J
Vends Susanne
Paludan Søren R
Hartmann Rune
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M109.002923
Published
2009-07-31
Epub
2009-00-20
Pages
20869-75
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2742852
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M109.002923 PMC Full Text View journal details
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