IL-22R, IL-10R2, and IL-22BP Binding Sites Are Topologically Juxtaposed on Adjacent and Overlapping Surfaces of IL-22
IL-22R, IL-10R2, and IL-22BP Binding Sites Are Topologically Juxtaposed on Adjacent and Overlapping Surfaces of IL-22
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DOI：
10.1016/j.jmb.2008.07.046
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发表时间：
2008-10-24
影响因子：
5.6
通讯作者：
Fouser, Lynette A.
中科院分区：
文献类型：
--
作者：
Wu, Paul W.;Li, Jing;Fouser, Lynette A.
白细胞介素（IL）22是一种II型细胞因子，由免疫细胞产生，作用于非免疫细胞以调节局部组织炎症。IL-22作为最近鉴定的CD 4（+）效应淋巴细胞的T辅助细胞17谱系的产物，在粘膜免疫以及在自身免疫性疾病中观察到的失调的炎症中起关键作用。我们使用综合诱变结合哺乳动物细胞表达，ELISA细胞为基础的，和结构的方法来评估IL-22如何与其细胞表面受体，IL-22 R/IL-10 R2，和分泌的IL-22结合蛋白相互作用。本研究鉴定了IL-22的那些氨基酸侧链，其对于与IL-22 R的最佳结合是单独重要的，显著扩展了与IL-10 R2结合所需的IL-22表面的定义，并证明了IL-22结合蛋白如何阻止IL-22 R与IL-22结合。IL-22 R和IL-10 R2结合位点在相邻的IL-22表面上并置，主要由螺旋A、D和IF以及环AB贡献。我们的研究结果还提供了一个模型，IL-19，IL-20，IL-24和IL-26是其他IL-10样细胞因子，如何与它们各自的细胞表面受体相互作用。(C)2008爱思唯尔有限公司保留所有权利。
Interleukin (IL) 22 is a type II cytokine that is produced by immune cells and acts on nonimmune cells to regulate local tissue inflammation. As a product of the recently identified T helper 17 lineage of CD4(+) effector lymphocytes, IL-22 plays a critical role in mucosal immunity as well as in dysregulated inflammation observed in autoimmune diseases. We used comprehensive mutagenesis combined with mammalian cell expression, ELISA cell-based, and structural methods to evaluate how IL-22 interacts with its cell surface receptor, IL-22R/IL-10R2, and with secreted IL-22 binding protein. This study identifies those amino acid side chains of IL-22 that are individually important for optimal binding to IL-22R, considerably expands the definition of IL-22 surface required for binding to IL-10R2, and demonstrates how IL-22 binding protein prevents IL-22R from binding to IL-22. The IL-22R and IL-10R2 binding sites are juxtaposed on adjacent IL-22 surfaces contributed mostly by helices A, D, and IF and loop AB. Our results also provide a model for how IL-19, IL-20, IL-24, and IL-26 which are other IL-10-like cytokines, interact with their respectively cell Surface receptors. (C) 2008 Elsevier Ltd. All rights reserved.