A model of the complex between interleukin-4 and its receptors.
A three-dimensional model of interleukin-4 (IL-4) bound to one molecule each of the high- and low-affinity receptors (IL-4R and IL-2R gamma) was built, using the crystal structure of the complex of human growth hormone (HGH) with its receptor (HGHR) as a starting model. The modeling of IL-4 with its receptors was based on the conservation of the sequences and on the predicted structural organization for cytokine receptors, and assuming that the binding mode of the ligands would be similar. Analysis of the interface between IL-4 and both receptor molecules was carried out to reveal which residues are important for complex formation. The modeling procedures showed that there were no major problems in maintaining a reasonable fit of IL-4 with the two receptor molecules, in a manner analogous to the complex of HGH-HGHR. Many of the residues that appear by modeling to be important for binding between IL-4 and the receptors have been previously implicated in that role by different methods. A striking motif of aromatic and positively charged residues on the surface of the C-terminal domains of the receptors is highly conserved in the structure of HGH-HGHR and in the models of IL-4 complexed with its receptors.
Gustchina
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A
NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Maryland 21702, USA.
Zdanov
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A
Schalk-Hihi
C
C
Wlodawer
A
A
D000595:Amino Acid Sequence; D013006:Growth Hormone / Q000378:metabolism; D015847:Interleukin-4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019948:Receptors, Interleukin-4; D011986:Receptors, Somatotropin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics
D018123:Receptors, Interleukin; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D011986:Receptors, Somatotropin; D015847:Interleukin-4; D013006:Growth Hormone