Cutting edge: Evidence for ligand-independent multimerization of the IL-17 receptor
Cutting edge: Evidence for ligand-independent multimerization of the IL-17 receptor
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DOI：
10.4049/jimmunol.176.2.711
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发表时间：
2006-01-15
影响因子：
4.4
通讯作者：
Gaffen, SL
中科院分区：
文献类型：
--
作者：
Kramer, JM;Yi, L;Gaffen, SL
IL-17 及其受体是新型炎症细胞因子家族的创始成员。迄今为止，仅鉴定出一种 IL-17 受体亚基，称为 IL-17RA。所有已知的细胞因子受体均由多个亚基的复合体组成。尽管 IL-17 家族细胞因子以同二聚体形式存在，但 IL-17P 复合物的构型和化学计量仍然未知。我们使用荧光共振能量转移 (FRET) 来确定 IL-17RA 亚基是否多聚化，如果是，则确定它们是否在质膜中预组装。共表达与青色或黄色荧光蛋白（CFP 或 YFP）融合的 IL-17RA 的 HEK293 细胞用于评估 IL-17A 或 IL-17F 处理前后的 FRET。在没有配体的情况下，IL-17RA 分子表现出显着的特异性 FRET 效率，证明它们存在于多聚体、预先形成的受体复合物中。引人注目的是，用 IL-17A 或 IL-17F 处理显着降低了 FRET 效率，表明 IL-17R 复合物内的 IL-IM 亚基在配体结合时发生构象变化。
IL-17 and its receptor are founding members of a novel inflammatory cytokine family. To date, only one IL-17 receptor subunit has been identified, termed IL-17RA. All known cytokine receptors consist of a complex of multiple subunits. Although IL-17-family cytokines exist as homodimers, the configuration and stoichiometry of the IL-17P complex remain unknown. We used fluorescence resonance energy transfer (FRET) to determine whether IL-17RA subunits multimerize, and, if so, whether they are preassembled in the plasma membrane. HEK293 cells coexpressing IL-17RA fused to cyan or yellow fluorescent proteins (CFP or YFP) were used to evaluate FRET before and after IL-17A or IL-17F treatment. In the absence of ligand, IL-17RA molecules exhibited significant specific FRET efficiency, demonstrating that they exist in a multimeric, preformed receptor complex. Strikingly, treatment with IL-17A or IL-17F markedly reduced FRET efficiency, suggesting that IL-IM subunits within the IL-17R complex undergo a conformational change upon ligand binding.