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Class II cytokines are small @a-helical signaling proteins that play an important role in many different processes. They are involved in immunological processes such as innate immune responses against bacteria and viruses as well as cell and tissue protection during inflammation. Disorders in class II cytokine production and function can cause autoimmunological diseases. Within recent years, several new cytokines were described in organisms other than mammals, and it seems that complex class II cytokines are present in teleost fish as well. Recently, our laboratory solved the crystal structures of two interferons from zebrafish showing that they are homologues of mammalian type I interferons (Hamming et al., 2011). Interleukin (IL)-22 is a class II cytokine belonging to the interleukin-10 family, a subclass within class II cytokines. Homologues of the human IL-22 gene have been described in other mammals, chicken, clawed frog and zebrafish. However, little functional data are currently available on piscine IL-22. We have solved the crystal structure of zebrafish IL-22 (zIL-22) at a resolution up to 2.1A. The structure of zIL-22 shows a typical class II cytokine conformation with the protein core formed by four out of six @a-helices (A, C, D, F) in up-up-down-down orientation. Comparison of the zIL-22 structure to structures of other class II cytokines showed that it is most similar to human IL-22 and IL-20. This indicates that zebrafish IL-22 protein is indeed a homologue of human IL-22. We generated structure-guided alignment of class II cytokines using the DALI server and available structures of members of this family. This alignment was used as a starting point for phylogenetic analysis and gave significant new insight into the evolution of the class II cytokine family. References: Hamming O. J., Lutfalla G., Levraud J.P., Hartmann R., (2011), Crystal structure of zebrafish interferons 1 and 2 reveals a conservation of type I interferon structure in vertebrates, J Virol., 85, 8181-8187
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