title: Structure-function analysis of interleukin-5 utilizing mouse/human chimeric molecules.
abstract: Interleukin-5 (IL5) is a T cell derived glycoprotein that stimulates eosinophil production and activation. In the mouse, but apparently not in the human, it is active on B cells. The murine and human IL5 polypeptides exhibit 70% sequence similarity and yet display distinct species-specific activity. Whilst mouse and human IL5 are equally active in human cell assays, human IL5 is 100-fold less active than murine IL5 in mouse cell assays. Two restriction sites were utilized to divide the human and mouse sequences into three fragments. Hybrid molecules consisting of all combinations of these fragments were constructed and expressed. In the human cell assays [using bone marrow or the erythroleukaemic cell line (TF-1)] all the hybrid proteins generated activity comparable to that of the human and mouse IL5. This implies that replacing different domains does not result in detrimental effects to the tertiary structure of the molecule. In the mouse cell assays [using bone marrow or the pro-B cell line (B13)] the hybrids clearly identified the importance of residues in the C terminus for biological activity. The changing of only eight residues in this region of human IL5, to those of mouse IL5, resulted in the hybrid producing biological activity comparable to mouse IL5. In addition, competition binding assays showed that this region probably interacts with the receptor.
authors.affiliation: National Institute for Medical Research, Mill Hill, London, UK.
authors.forename: A N
authors.initials: AN
authors.lastname: McKenzie
authors.forename: S C
authors.initials: SC
authors.lastname: Barry
authors.forename: M
authors.initials: M
authors.lastname: Strath
authors.forename: C J
authors.initials: CJ
authors.lastname: Sanderson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D015848:Interleukin-5; D011994:Recombinant Proteins