Mapping receptor binding sites in interleukin (IL)-1 receptor antagonist and IL-1 beta by site-directed mutagenesis. Identification of a single site in IL-1ra and two sites in IL-1 beta
| Autor: | R J, Evans, J, Bray, J D, Childs, G P, Vigers, B J, Brandhuber, J J, Skalicky, R C, Thompson, S P, Eisenberg |
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| Rok vydání: | 1995 |
| Předmět: |
Models
Molecular Binding Sites Magnetic Resonance Spectroscopy Sequence Homology Amino Acid Thymoma Protein Conformation Sialoglycoproteins Molecular Sequence Data Receptors Interleukin-1 CHO Cells Thymus Neoplasms Binding Competitive Recombinant Proteins Rats Interleukin 1 Receptor Antagonist Protein Mice Cricetinae Escherichia coli Mutagenesis Site-Directed Tumor Cells Cultured Animals Point Mutation Amino Acid Sequence Cloning Molecular Interleukin-1 |
| Zdroj: | The Journal of biological chemistry. 270(19) |
| ISSN: | 0021-9258 |
| Popis: | Interleukin-1 receptor antagonist (IL-1ra), an IL-1 family member, binds with high affinity to the type I IL-1 receptor (IL-1RI), blocking IL-1 binding but not inducing an IL-1-like response. Extensive site-directed mutagenesis has been used to identify residues in IL-1ra and IL-1 beta involved in binding to IL-1RI. These analyses have revealed the presence of two discrete receptor binding sites on IL-1 beta. Only one of these sites is present on IL-1ra, consisting of residues Trp-16, Gln-20, Tyr-34, Gln-36, and Tyr-147. Interestingly, the absent second site is at the location of the major structural difference between IL-1ra and IL-1 beta, which are otherwise structurally similar. The two receptor binding sites on IL-1 beta are also present on IL-1 alpha. Thus, it appears that the two IL-1 agonist molecules have two sites for IL-1RI binding, and the homologous antagonist molecule, IL-1ra, has only one. Based on these observations, a hypothesis is presented to account for the difference in activity between the agonist and antagonist proteins. It is proposed that the presence of the two receptor binding sites may be necessary for agonist activity. |
| Databáze: | OpenAIRE |
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