Crystal structure of the IL-15-IL-15Rα complex, a cytokine-receptor unit presented in trans
Crystal structure of the IL-15-IL-15Rα complex, a cytokine-receptor unit presented in trans
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DOI：
10.1038/ni1492
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发表时间：
2007-09-01
影响因子：
30.5
通讯作者：
Ikemizu, Shinji
中科院分区：
文献类型：
--
作者：
Chirifu, Mami;Hayashi, Chiharu;Ikemizu, Shinji
白细胞介素15（IL-15）和IL-2分别促进记忆性CD 8（+）T细胞和调节性T细胞的存活，结合共享β和γ信号亚基的受体复合物。受体特异性由独特的非信号α亚基提供。尽管IL-2受体-α（IL-2 R α）在T细胞和B细胞上与β-和γ-亚基一起顺式表达，但IL-15 R α在抗原呈递细胞上反式表达。在这里，我们提出了一个1.85埃的晶体结构的人IL-15-IL-15 R α复合物。该结构提供了深入了解细胞因子识别的特异性的分子基础，并强调了水在产生这种非常高亲和力的复合物中的重要性。尽管IL-15-IL-2序列同源性非常低且受体结构不同，但IL-15-IL-15 Ra和IL-2-IL-2 Ra复合物的拓扑结构非常相似。我们的数据提出了IL-2，像IL-15一样，可能能够在其独特的受体α链的背景下反式呈递的可能性。
Interleukin 15 (IL-15) and IL-2, which promote the survival of memory CD8(+) T cells and regulatory T cells, respectively, bind receptor complexes that share beta- and gamma-signaling subunits. Receptor specificity is provided by unique, nonsignaling alpha-subunits. Whereas IL-2 receptor-alpha (IL-2R alpha) is expressed together in cis with the beta- and gamma-subunits on T cells and B cells, IL-15R alpha is expressed in trans on antigen-presenting cells. Here we present a 1.85-angstrom crystal structure of the human IL-15-IL-15R alpha complex. The structure provides insight into the molecular basis of the specificity of cytokine recognition and emphasizes the importance of water in generating this very high-affinity complex. Despite very low IL-15-IL-2 sequence homology and distinct receptor architecture, the topologies of the IL-15-IL-15R alpha and IL-2-IL-2R alpha complexes are very similar. Our data raise the possibility that IL-2, like IL-15, might be capable of being presented in trans in the context of its unique receptor a-chain.