Binding of Type I IL-1β Receptor Fragment 151–162 to Interleukin-1β

Abstract

The relevance of hydropathically complementary sequences in ligand receptor interactions has been evaluated in the interleukin-1 beta/receptor type I case. Computer assisted comparison of the hydropathic profiles of IL-1 beta and its receptor (type I) identified residues 88-99 in IL-1 beta and 151-162 in the receptor as the sequences pair characterized by the highest level of hydropathic complementarity. These fragments, once produced by chemical synthesis and derivatized with biotin, displayed specific recognition properties for each other, as detected by solid phase binding assays. Binding between the two fragments occurred independently from the assay format, was saturable and specifically inhibited by unlabeled peptides. Receptor fragment (151-162) derivatized with biotin recognized also full length recombinant IL-1 beta, and binding was inhibited to 50% in the presence of 3 microM IL-1 beta (88-99) peptide. Interaction specificity was further confirmed by the non competitive effect on the interaction of a sequence scrambled IL-1 beta (88-99) peptide. In a similar way, full length biotinylated IL-1 beta recognized immobilized IL-1 beta receptor fragment (151-162), and this interaction was diminished in the presence of unlabeled receptor fragment or IL-1 beta Results indicate that IL-1 beta receptor fragment (151-162) binds IL-1 beta recognizing the IL-1 beta (88-99) sequence, thus suggesting a possible role of these fragments in the protein/receptor recognition surface.