Substitutions at the Glu62 residue of human interleukin-2 differentially affect its binding to the alpha chain and the beta gamma complex of the interleukin-2 receptor.

Abstract

Human interleukin-2 (IL-2) alpha helix B is more conserved than the whole molecule, but has been less studied than other alpha helices of IL-2. Using site-directed mutagenesis, several IL-2 mutants in this helix were obtained. We found that the IL-2 mutant containing Leu at position 62 (Leu62-IL-2) loses its ability to bind IL-2 receptor subunit alpha (IL-2R alpha), but retains binding affinity to IL-2R subunit beta gamma as well as some bioactivity; nevertheless, another substitution at the same residue, Arg62IL-2, loses its binding ability to both IL-2R alpha and IL-2R beta gamma, and can no longer stimulate IL-2-dependent cell growth, showing that Glu62 not only takes part in IL-2R alpha binding, but can also affect IL-2 binding to IL-2R beta gamma. In this regard, Glu62 may be a key site in the IL-2/IL-2R alpha interaction, and can facilitate IL-2R ternary-complex formation, leading to IL-2R alpha-mediated, IL-2-stimulated signal transduction.