Identification of specific residues of human interleukin 2 that affect binding to the 70-kDa subunit (p70) of the interleukin 2 receptor
| Autor: | L Collins, G Ju, D V Weber, C Seals, W H Tsien, V Toome, John Hakimi, P Bailon, Warner C. Greene, J Hoskings |
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| Rok vydání: | 1988 |
| Předmět: |
Receptor complex
Multidisciplinary Circular Dichroism Protein subunit Interleukin 5 receptor alpha subunit hemic and immune systems Receptors Interleukin-2 Biology Binding Competitive Gamma-aminobutyric acid receptor subunit alpha-1 Molecular biology Chromatography Affinity Recombinant Proteins Cell Line Interleukin 10 receptor alpha subunit Protein structure Biochemistry Interleukin 26 Mutation Escherichia coli Humans Interleukin-2 Interleukin 12 receptor beta 1 subunit Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 85:7709-7713 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.85.20.7709 |
| Popis: | Analogs of interleukin 2 containing defined amino acid substitutions and deletions were assayed for bioactivity and for competitive binding to the high-affinity human interleukin 2 receptor complex and its two component subunits, a 55-kDa subunit (p55 or TAC) and a 70-kDa subunit (p70). Substitution of Asp20 or deletion of Phe124 resulted in inactive analog proteins that were unable to interact with the high-affinity p55/p70 complex or the intermediate-affinity p70 subunit of the interleukin 2 receptor. These analogs, however, retained the capacity to compete for binding to the low-affinity p55 subunit. The presence of the carboxylic acid in the side chain of Asp20 was necessary for effective binding to the p70 protein. In contrast, substitution of Trp121 and Leu17 created analogs that were inactive in the bioassay and all three binding assays. The effects of these mutations on protein conformation were assessed by circular dichroism. These results demonstrate that specific residues in the NH2 and COOH termini of interleukin 2 are crucial for its structure and activity. |
| Databáze: | OpenAIRE |
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