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 interleukin-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 A between different cytokines, about twice the differences observed for independently determined crystal and solution structures of IL-4. Considerable similarity in amino acid sequence in the areas expected to interact with the receptors was detected, and the available mutagenesis data for these cytokines were correlated with structure conservation. Models of cytokine-receptor interactions were postulated for IL-4 based on its structure as well as on the published structure of human growth hormone interacting with its receptors (de Vos, A.M., Ultsch, M., & Kossiakoff, A.A., 1992, Science 255, 306-312). Patches of positively charged residues on the surfaces of helices C and D of IL-4 may be responsible for the interactions with the negatively charged residues found in the complementary parts of the IL-4 receptors.
Wlodawer
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Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702.
Pavlovsky
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Gustchina
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D000595:Amino Acid Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray; D016207:Cytokines / Q000737:chemistry* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry; D006410:Hematopoiesis; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry; D015847:Interleukin-4 / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D018121:Receptors, Cytokine / Q000378:metabolism*
D016207:Cytokines; D007376:Interleukin-2; D018121:Receptors, Cytokine; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor