Ovine interferon (IFN) is a type I interferon that was originally identified as ovine trophoblast protein and is associated with the maternal recognition of pregnancy in sheep. Additionally, IFN possesses potent antiviral and antiproliferative activity without the corresponding toxicity found in known IFNs. Structure-function studies with synthetic peptides have identified three discontinuous functional sites on the protein that are involved in receptor interaction and biological activity. However, the structural relationship of these regions is unknown. Therefore, a model of the 3-D structure of IFN would be useful in interpretation of existing data and the design of future structurefunction studies. Combining information from circular dichroism (CD) of both the full length recombinant IFNT and ynthetic peptides representing regions of the IFN molecule, with sequence homology of IFN to IFN ,a protein of known 3-D structure, we have constructed a model of IFN using dis ance geometry and energy minimization methods. The most striking feature of this model is that functionally active domains of IFN, discontinuous in the primary structure, are localized to one side of the molecule and found to be spatially contiguous. This observation is consistent with multiple binding sites on IFNT interacting simultaneously with the IFN receptor. 1994 Oxford University Press.
