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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A potent dimeric peptide antagonist of interleukin-5 that binds two interleukin-5 receptor α chains
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A potent dimeric peptide antagonist of interleukin-5 that binds two interleukin-5 receptor α chains

机译：一种有效的白介素5二聚体肽拮抗剂，可与两条白介素5受体α链结合

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摘要

Two series of peptides that specifically bind to the extracellular domain of the α chain of the human interleukin-5 receptor (IL-5Rα), but share no primary sequence homology to IL-5, were identified from libraries of random recombinant peptides. Affinity matura- tion procedures generated a 19-aa peptide that binds to the IL-5 receptor α/β heterodimer complex with an affinity equal to that of IL-5 and is a potent and specific antagonist of IL-5 activity in a human eosinophil adhesion assay. The active form of the peptide is a disulfide-crosslinked dimer that forms spontaneously in solu- tion. Gel filtration analysis, receptor-binding studies, and analytical ultracentrifugation reveal that the dimeric peptide binds simulta- neously to two receptor α chains in solution. Furthermore, the dimer peptide, but not IL-5, can activate a chimeric receptor consisting of the IL-5Rα extracellular domain fused to the intra- cellular domain of the epidermal growth factor receptor, thus demonstrating that the peptide also promotes receptor dimeriza- tion in a cellular context. The functional antagonism produced by the bivalent interaction of the dimeric peptide with two IL-5Rα chains represents a distinctive mechanism for the antagonism of cytokines that use heteromeric receptors.
机译：从随机重组肽文库中鉴定出了两个与人白介素5受体（IL-5Rα）的α链胞外域特异性结合但不与IL-5共有一级序列同源性的肽。亲和力成熟程序产生了一个19-aa肽，该肽以与IL-5亲和力相等的亲和力与IL-5受体α/β异二聚体复合物结合，并且是人类嗜酸性粒细胞中有效的，特异性的IL-5拮抗剂。粘附测定。肽的活性形式是在溶液中自发形成的二硫键交联的二聚体。凝胶过滤分析，受体结合研究和分析超速离心分析表明，二聚体肽与溶液中的两个受体α链同时结合。此外，二聚体肽可激活由与表皮生长因子受体的胞内结构域融合的IL-5Rα胞外结构域组成的嵌合受体，而不是IL-5，从而表明该肽还促进受体二聚化。在蜂窝环境中。由二聚体肽与两条IL-5Rα链的二价相互作用产生的功能拮抗作用代表了使用异聚受体的细胞因子拮抗作用的独特机制。

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