Jones Brandi C, Logsdon Naomi J, Walter Mark R
Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Structure. 2008 Sep 10;16(9):1333-44. doi: 10.1016/j.str.2008.06.005. Epub 2008 Jul 3.
IL-22 is an IL-10 family cytokine that initiates innate immune responses against bacterial pathogens and contributes to immune disease. IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1 and IL-10R2 receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22R1 also pairs with the IL-20R2 chain to induce IL-20 and IL-24 signaling. To define the molecular basis of these diverse interactions, we have determined the structure of the IL-22/sIL-22R1 complex. The structure, combined with homology modeling and surface plasmon resonance studies, defines the molecular basis for the distinct affinities and specificities of IL-22 and IL-10 receptor chains that regulate cellular targeting and signal transduction to elicit effective immune responses.
白细胞介素-22（IL-22）是一种白细胞介素-10家族细胞因子，可启动针对细菌病原体的固有免疫反应，并与免疫疾病相关。IL-22的生物活性通过与由IL-22R1和IL-10R2受体链组成的细胞表面复合物结合而启动，并通过与可溶性结合蛋白IL-22BP的相互作用进一步调节，IL-22BP与IL-22R1的细胞外区域（sIL-22R1）具有序列相似性。IL-22R1还与IL-20R2链配对以诱导IL-20和IL-24信号传导。为了确定这些不同相互作用的分子基础，我们测定了IL-22/sIL-22R1复合物的结构。该结构与同源建模和表面等离子体共振研究相结合，确定了调节细胞靶向和信号转导以引发有效免疫反应的IL-22和IL-10受体链不同亲和力和特异性的分子基础。
