title: 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.
authors.affiliation: Shanghai Institute of Biochemistry, Academia Sinica, P.R. China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Zheng
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.forename: X
authors.initials: X
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003001:Cloning, Molecular; D005973:Glutamine; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry* / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007376:Interleukin-2; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D005973:Glutamine