Crystal structures of interleukin 17A and its complex with IL-17 receptor A
Crystal structures of interleukin 17A and its complex with IL-17 receptor A
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DOI：
10.1038/ncomms2880
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发表时间：
2013-05-01
影响因子：
16.6
通讯作者：
Griffor, Matthew C.
中科院分区：
文献类型：
--
作者：
Liu, Shenping;Song, Xi;Griffor, Matthew C.
白细胞介素-17家族的组成多肽形成六种不同的同型二聚体细胞因子（IL-17 A-F）和异源二聚体IL-17 A/F。它们与IL-17受体A-E（IL-17 RA-E）的相互作用介导宿主防御，同时也有助于炎症和自身免疫反应。IL-17 A和IL-17 F都优先结合含有一个IL-17 RA分子和一个IL-17 RC分子的受体复合物。更一般地，IL-17 RA似乎是与其家族的其他成员配对以允许不同IL-17细胞因子的信号传导的共享受体。在这里，我们报告了同源二聚体IL-17 A及其与IL-17 RA的复合物的晶体结构。在IL-17 A分子的一侧与IL-17 RA结合诱导IL-17 A的第二个与免疫相关的受体位点的构象变化。这种变化有利于并足以解释选择不同的受体多肽来完成精氨酸-受体复合物。结构结果得到了生物物理学研究的支持，IL-17 A变体通过定点诱变产生。
The constituent polypeptides of the interleukin-17 family form six different homodimeric cytokines (IL-17A-F) and the heterodimeric IL-17A/F. Their interactions with IL-17 receptors A-E (IL-17RA-E) mediate host defenses while also contributing to inflammatory and autoimmune responses. IL-17A and IL-17F both preferentially engage a receptor complex containing one molecule of IL-17RA and one molecule of IL-17RC. More generally, IL-17RA appears to be a shared receptor that pairs with other members of its family to allow signaling of different IL-17 cytokines. Here we report crystal structures of homodimeric IL-17A and its complex with IL-17RA. Binding to IL-17RA at one side of the IL-17A molecule induces a conformational change in the second, symmetry-related receptor site of IL-17A. This change favors, and is sufficient to account for, the selection of a different receptor polypeptide to complete the cytokine-receptor complex. The structural results are supported by biophysical studies with IL-17A variants produced by site-directed mutagenesis.