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. 1991 Apr 1;88(7):2658–2662. doi: 10.1073/pnas.88.7.2658

Conversion of the interleukin 1 receptor antagonist into an agonist by site-specific mutagenesis.

G Ju 1, E Labriola-Tompkins 1, C A Campen 1, W R Benjamin 1, J Karas 1, J Plocinski 1, D Biondi 1, K L Kaffka 1, P L Kilian 1, S P Eisenberg 1, et al.
PMCID: PMC51297  PMID: 1826365

Abstract

Interleukin 1 (IL-1) receptor antagonist (IL-1ra) is a naturally occurring protein that binds to the IL-1 receptor present on T cells, fibroblasts, and other cell types and acts to block IL-1-induced responses. IL-1ra is a pure antagonist and has no agonist activity in in vitro or in vivo systems. By site-specific mutagenesis, an analog of IL-1ra was created that contained a substitution of a single amino acid, Lys-145----Asp. This analog, IL-1ra K145D, exhibited partial agonist activity in the D10.G4.1 cell proliferation assay. The newly acquired agonist activity could not be neutralized by antisera to IL-1 alpha or IL-1 beta, but it could be blocked by a monoclonal antibody to the T-cell IL-1 receptor. The analog also showed agonist activity as assayed by increased prostaglandin E2 synthesis from CHO cells expressing recombinant mouse IL-1 receptor. These results with IL-1ra K145D demonstrate the importance of the region surrounding the corresponding Asp-145 residue in IL-1 beta for triggering the biological response to IL-1.

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Selected References

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