Stoichiometry of the complex of human interleukin-4 with its receptor.
A large number of cytokines have been shown to possess a four-helix bundle structure with a unique up-up-down-down connectivity. The receptors for this family of cytokines have been shown to be homologous as well, each possessing two tandem repeats of a fibronectin type III-like domain. The crystal structure of human growth hormone bound to the soluble portion of its receptor has served as the only experimentally-determined example of the interaction between the four-helix bundle cytokines and their receptors: two identical receptor subunits bind to different epitopes on the same growth hormone ligand. We have conducted a series of experiments to determine if this structural paradigm is true for interleukin-4 and interleukin-4 receptor. Native polyacrylamide gel electrophoresis and gel filtration chromatography reveal that interleukin-4 forms a tight 1:1 complex with the system.
Immunex Corporation, Seattle, WA 98101.
R C
RC
Hoffman
C
C
Schalk-Hihi
B J
BJ
Castner
M G
MG
Gibson
B D
BD
Rasmussen
A
A
Zdanov
A
A
Gustchina
C J
CJ
March
A
A
Wlodawer
D013006:Growth Hormone / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000737:chemistry* / Q000378:metabolism; D046911:Macromolecular Substances; D011485:Protein Binding; D011487:Protein Conformation; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000737:chemistry* / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000737:chemistry / Q000378:metabolism
D046911:Macromolecular Substances; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011986:Receptors, Somatotropin; D015847:Interleukin-4; D013006:Growth Hormone