BINDING OF TYPE-I IL-1-BETA RECEPTOR FRAGMENT-151-162 TO INTERLEUKIN-1-BETA

The relevance of hydropathically complementary sequences in ligand rec eptor interactions has been evaluated in the interleukin-1 beta/recept or type I case. Computer assisted comparison of the hydropathic profil es 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 character ized by the highest level of hydropathic complementarity. These fragme nts, 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 occur red independently from the assay format, was saturable and specificall y inhibited by unlabeled peptides. Receptor fragment (151-162) derivat ized with biotin recognized also full length recombinant IL-1 beta, an d binding was inhibited to 50% in the presence of 3 mu M 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 be ta (88-99) peptide. In a similar way, full length biotinylated IL-1 be ta recognized immobilized IL-1 beta receptor fragment (151-162), and t his interaction was diminished in the presence of unlabeled receptor f ragment or IL-1 beta. Results indicate that IL-1 beta receptor fragmen t (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/re ceptor recognition surface.