HEMATOPOIETIC CYTOKINES - SIMILARITIES AND DIFFERENCES IN THE STRUCTURES, WITH IMPLICATIONS FOR RECEPTOR-BINDING

Crystal and NMR structures of helical cytokines-interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interle ukin-2 (IL-2)-have been compared. Root mean square deviations in the C (alpha) coordinates for the conserved regions of the helices were 1-2 angstrom between different cytokines, about twice the differences obse rved for independently determined crystal and solution structures of I L-4. Considerable similarity in amino acid sequence in the areas expec ted to interact with the receptors was detected, and the available mut agenesis data for these cytokines were correlated with structure conse rvation. Models of cytokine-receptor interactions were postulated for IL-4 based on its structure as well as on the published structure of h uman growth hormone interacting with its receptors (de Vos, A.M., Ults ch, M., & Kossiakoff, A.A., 1992, Science 255, 306-312). Patches of po sitively charged residues on the surfaces of helices C and D of IL-4 m ay be responsible for the interactions with the negatively charged res idues found in the complementary parts of the IL-4 receptors.