ABSTRACT

The interferons (IFNs) were discovered in 1957 by Isaacs and Lindenman when they observed that a substance secreted by virally infected cells could protect other cells from viral infection. The interferons IFN-β, IFN-α-2, and several other cytokines including Interleukin-2 (IL-2), Interleukin 4 (IL-4), growth hormone, and Granulocyte-macrophage colony stimulating factor (GM-CSF) belong to a family in which all share a four-helix bundle structural motif. The structure of IFN-τ was also examined by Circular dichroism (CD). Analysis of the IFN-τ spectra predicts that the secondary structural elements derived from CD spectra indicate approximately 70% α-helix. The production of IFN-γ-neutralizing antibodies specific for an N-terminal peptide of human IFN-γ provided the first evidence that the N-terminus of IFN-γ contained an important functional site. This chapter reviews some of the structure/function studies that have begun to elucidate important features of IFN activity and form a basis for future rational drug design.