Human IL-21 and IL-4 bind to partially overlapping epitopes of common gamma-chain.
Interleukin 21 (IL-21) is a recently identified novel cytokine that plays an important role in the regulation of B, T, and NK cell functions. Its effects depend on binding to and signaling through an IL-21 receptor complex consisting of the IL-21 receptor (IL-21R) and the common gamma-chain (gamma(c)). In this study using biosensor technique, the ligand-binding properties of IL-21R and gamma(c), which are presently poorly understood on a molecular level, were analyzed employing recombinant ectodomains of IL-21R and gamma(c). The formation of a binary complex between IL-21 and immobilized IL-21R (K(D) 70pM), gamma(c) and immobilized IL-21 (K(D) 160 microM) and a ternary complex between gamma(c) and IL-21 saturated immobilized IL-21R (K(D) 160nM) could be analyzed. The gamma(c) residues involved in IL-21 binding were defined by alanine-scanning mutational analysis. The epitope comprises gamma(c) residues N44, Y103, N128, L161, E162, and L208. It is not identical but partially overlapping with the previously established gamma(c) epitope for IL-4 binding. These results open the way to understand the molecular recognition mechanism in the IL-21 receptor system and also the promiscuous binding properties of gamma(c).
Zhang
Jin-Li
JL
Theodor-Boveri-Institut für Biowissenschaften, Biozentrum, Physiologische Chemie II, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany. zhang@biozentrum.uni-wuerzburg.de
Foster
Don
D
Sebald
Walter
W
D000595:Amino Acid Sequence; D001665:Binding Sites; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit; D053738:Interleukin-21 Receptor alpha Subunit; D015847:Interleukin-4 / Q000737:chemistry / Q000378:metabolism*; D007378:Interleukins / Q000737:chemistry / Q000378:metabolism*; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D018123:Receptors, Interleukin / Q000378:metabolism; D053655:Receptors, Interleukin-21; D020395:Receptors, Interleukin-7 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D000098546:Interleukin-21
D000939:Epitopes; C508117:IL21R protein, human; C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D046911:Macromolecular Substances; D018123:Receptors, Interleukin; D053655:Receptors, Interleukin-21; D020395:Receptors, Interleukin-7; D015847:Interleukin-4; D000098546:Interleukin-21