Sequence and structural relationships in the cytokine family.

The sequences of nine different cytokines, growth hormone, and prolactin have been aligned and their secondary structure predicted. The alignment reveals that each exon has a characteristic sequence pattern shared by all cytokines. The most striking sequence similarity is observed in exon 4, where the residue pair Phe-Leu is conserved in many cytokines. In addition, there are discreet homologous regions between two specific growth factors, including a high degree of homology between granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3). The secondary structure analysis predicts that exon 3 of all cytokines has an antiparallel helix-turn-helix motif, which is likely to form the central helical segments of a four alpha-helical bundle-type structure. Based on the secondary structure and the disulfide-bonding pattern, the topological connectivity for a number of cytokines has been predicted.