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发表于 2013-12-18 08:25:28
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认领第 104 篇论文。
104. Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15.
Ring AM, Lin JX, Feng D, Mitra S, Rickert M, Bowman GR, Pande VS, Li P, Moraga I, Spolski R, Ozkan E, Leonard WJ, Garcia KC.
Natural Immunology (Dec 2012)
关于 IL-2 和 IL-15 功能分歧的机制和结构特点的见解
Ring AM, Lin JX, Feng D, Mitra S, Rickert M, Bowman GR, Pande VS, Li P, Moraga I, Spolski R, Ozkan E, Leonard WJ, Garcia KC 发表于《自然免疫学(Natural Immunology)》2012 年 12 月刊
SUMMARY.
概要
This is a continuation of paper #100, “Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’”. Our results provide new insights for the development of new specific therapeutics based on interleukin.
本篇论文是第 100 篇论文“Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’”的延续。我们的研究提供了基于白介素(interleukin)开发特异性免疫治疗的新观点。
ABSTRACT.
摘要
Interleukin 15 (IL-15) and IL-2 have distinct immunological functions even though both signal through the receptor subunit IL-2Rβ and the common γ-chain (γ(c)). Here we found that in the structure of the IL-15-IL-15Rα-IL-2Rβ-γ(c) quaternary complex, IL-15 binds to IL-2Rβ and γ(c) in a heterodimer nearly indistinguishable from that of the IL-2-IL-2Rα-IL-2Rβ-γ(c) complex, despite their different receptor-binding chemistries. IL-15Rα substantially increased the affinity of IL-15 for IL-2Rβ, and this allostery was required for IL-15 trans signaling. Consistent with their identical IL-2Rβ-γ(c) dimer geometries, IL-2 and IL-15 showed similar signaling properties in lymphocytes, with any differences resulting from disparate receptor affinities. Thus, IL-15 and IL-2 induced similar signals, and the cytokine specificity of IL-2Rα versus IL-15Rα determined cellular responsiveness. Our results provide new insights for the development of specific immunotherapeutics based on IL-15 or IL-2.
虽然白介素 15(Interleukin 15,简称 IL-15)和白介素 2(IL-2)的信号都是通过受体的 IL-2Rβ 和常见的 γ-chain(γ-链,简称 γ(c))传递,它们具有不同的免疫功能。本研究发现 IL-15–IL-15Rα–IL-2Rβ–γ(c) 四聚体复合物的结构,其中 IL-15 结合 IL-2Rβ 和 γ(c) 形成异二聚体,几乎与 IL-2–IL-2Rα–IL-2Rβ–γ(c) 复合物的结构没什么差别,尽管它们具有不同的受体结合化学反应。IL-15Rα 大幅增加 IL-15 与 IL-2Rβ 的亲和力,并且这种变构效应是 IL-15 反式信号传导所必需的。与它们完全相同的 IL-2Rβ–γ(c) 二聚体空间构型一致的是,IL-2 和 IL-15 虽然具有不同的受体亲和性,但它们在淋巴细胞中表现出相似的信号特性,没有什么不同。总之,IL-15 和 IL-2 诱导了相似的信号,IL-2Rα 与 IL-15Rα 的细胞因子特异性决定了它们的细胞响应。我们的研究提供了基于 IL-15 或 IL-2 开发特异性免疫治疗的新观点。
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备注:经搜索发现“生物文库”网站已有介绍翻译,链接在此 http://www.bioku.cn/201303/nature-immunology-interleukin2-il-2-il-15-functional-dichotomy/ ,本贴文字在“生物文库”译文基础上略有修改。
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