A single amino acid difference between human and monkey interleukin (IL)-1beta dictates effective binding to soluble type II IL-1 receptor.
Soluble type II interleukin (IL)-1 receptor (sIL1R-II) binds human IL-1beta with high affinity and neutralizes its activity. Recombinant sIL1R-II is considered a potentially useful anti-IL-1 therapeutic, and preclinical studies have been undertaken with this molecule in primates. To better understand the cytokine-receptor interactions occurring in this nonhuman context, monkey IL-1 and IL1R-II were cloned, and their binding abilities were examined in vitro. IL-1beta from cynomolgus monkey was capable of binding and activating the human type I IL-1 receptor. However, unlike human IL-1beta, it was unable to effectively bind and become neutralized by sIL1R-II. Human and cynomolgus IL-1beta proteins are 96% identical, differing by only six amino acids. Structural and mutational analysis revealed that the unique sIL1R-II binding ability of human IL-1beta is due to a single amino acid difference compared with monkey IL-1beta.
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D002455:Cell Division; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000737:chemistry* / Q000378:metabolism*; D008252:Macaca fascicularis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011485:Protein Binding; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D016207:Cytokines; D018076:DNA, Complementary; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins