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. 1991 Dec 15;88(24):11182–11186. doi: 10.1073/pnas.88.24.11182

Identification of the discontinuous binding site in human interleukin 1 beta for the type I interleukin 1 receptor.

E Labriola-Tompkins 1, C Chandran 1, K L Kaffka 1, D Biondi 1, B J Graves 1, M Hatada 1, V S Madison 1, J Karas 1, P L Kilian 1, G Ju 1
PMCID: PMC53098  PMID: 1837145

Abstract

Human interleukin 1 beta (IL-1 beta) exerts its diverse biological effects by binding to specific receptors on target cells. Two types of IL-1 receptor (IL-1R) have been identified: the type I IL-1R (p80) and the type II IL-1R (p68). Using site-specific mutagenesis, we have identified the binding site on IL-1 beta for the murine type I IL-1R. Analogs of the IL-1 beta protein containing defined amino acid substitutions were produced and tested for competitive binding to the two IL-1Rs. Substitutions of the amino acids at seven positions resulted in analogs that had greater than or equal to 100-fold reductions in competitive binding to the type I IL-1R, while maintaining substantial binding to the type II IL-1R. These seven amino acids (Arg-4, Leu-6, Phe-46, Ile-56, Lys-93, Lys-103, and Glu-105) are clustered in the IL-1 beta molecule, forming a discontinuous binding site. The side chains of all seven residues are exposed on the surface of IL-1 beta. The cumulative binding energies contributed by each of the residues predict a binding affinity that is consistent with the observed Kd of the wild-type protein for the type I IL-1R.

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Selected References

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