| Autor: |
Labriola-Tompkins, E, Chandran, C, Kaffka, K L, Biondi, D, Graves, B J, Hatada, M, Madison, V S, Karas, J, Kilian, P L, Ju, G |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; December 1991, Vol. 88 Issue: 24 p11182-11186, 5p |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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