DC Field | Value | Language |
---|---|---|
dc.contributor.author | Soo Hyun Kim | - |
dc.contributor.author | Tania Azam | - |
dc.contributor.author | Daniela Novick | - |
dc.contributor.author | Do Young Yoon | - |
dc.contributor.author | Leonid L Reznikov | - |
dc.contributor.author | Philip Burfler | - |
dc.contributor.author | Menachem Rubinstein | - |
dc.contributor.author | Charles A Dinarello | - |
dc.date.accessioned | 2017-04-19T08:58:58Z | - |
dc.date.available | 2017-04-19T08:58:58Z | - |
dc.date.issued | 2002 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | 10.1074/jbc.M108311200 | ko |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/5805 | - |
dc.description.abstract | Interleukin-18 (IL-18) is a pro-inflammatory cytokine, and IL-18-binding protein (IL-18BP) is a naturally occurring protein that binds IL-18 and neutralizes its biological activities. Computer modeling of human IL-18 identified two charged residues, Glu-42 and Lys-89, which interact with oppositely charged amino acid residues buried in a large hydrophobic pocket of IL-18BP. The cell surface IL-18 receptor a chain competes with IL-18BP for IL-18 binding, although the IL-18 receptor α chain does not share significant homology to IL-18BP. In the present study, Glu-42 was mutated to Lys and Lys-89 to Glu; Glu-42 and Lys-89 were also deleted separately. The deletion mutants (E42X and K89X) were devoid of biological activity, and the K89E mutant lost 95% of its activity. In contrast, compared with wild-type (WT) IL-18, the E42K mutant exhibited a 2-fold increase in biological activity and required a 4-fold greater concentration of IL-18BP for neutralization. The binding of WT IL-18 and its various mutants to human natural killer cells was evaluated by competition assays. The mutant E42K was more effective than WT IL-18 in inhibiting the binding of 125I-IL-18 to natural killer cells, whereas the three inactive mutants E42X, K89E, and K89X were unable to compete with 125I-IL-18 for binding. Similarly, WT IL-18 and the E42K mutant induced degradation of Iκ-Bα, whereas the three biologically inactive mutants did not induce degradation. The present study reveals that Glu-42 and Lys-89 are critical amino acid residues for the integrity of IL-18 structure and are important for binding to cell surface receptors, for signal transduction, and for neutralization by IL-18BP. | - |
dc.publisher | Elsevier | - |
dc.title | Identification of amino acid residues critical for biological activity in human interleukin-18 | - |
dc.title.alternative | Identification of amino acid residues critical for biological activity in human interleukin-18 | - |
dc.type | Article | - |
dc.citation.title | Journal of Biological Chemistry | - |
dc.citation.number | 13 | - |
dc.citation.endPage | 11003 | - |
dc.citation.startPage | 10998 | - |
dc.citation.volume | 277 | - |
dc.contributor.affiliatedAuthor | Do Young Yoon | - |
dc.contributor.alternativeName | 김수현 | - |
dc.contributor.alternativeName | Azam | - |
dc.contributor.alternativeName | Novick | - |
dc.contributor.alternativeName | 윤도영 | - |
dc.contributor.alternativeName | Reznikov | - |
dc.contributor.alternativeName | Burfler | - |
dc.contributor.alternativeName | Rubinstein | - |
dc.contributor.alternativeName | Dinarello | - |
dc.identifier.bibliographicCitation | Journal of Biological Chemistry, vol. 277, no. 13, pp. 10998-11003 | - |
dc.identifier.doi | 10.1074/jbc.M108311200 | - |
dc.description.journalClass | Y | - |
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