STRUCTURAL STUDIES ON CYTOKINE-RECEPTOR COMPLEXES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们工作的总体目标是定义2类细胞因子信号的结构基础。在这个提案中，我们寻求定义介导IL-20信号的受体组装的结构。IL-20与IL-20R1和IL-20R2形成三元复合体，IL-20R1和IL-20R2是细胞表面受体，通过STAT3传递信号。到目前为止，还没有关于2类细胞因子的三元受体复合体的报道。IL-20的生物学特性表明，它调节免疫细胞和上皮细胞之间的串扰。最近的数据表明，IL-20在银屑病的发病机制中起关键作用，并可能成为控制银屑病的靶点。IL-20/IL-20R1/IL-20R2复合体的成功建成将成为2类细胞因子三元复合体的三维原型结构，并可用于设计治疗银屑病的新疗法。该络合物的晶体已经生长出来。需要同步辐射来筛选晶体，获得尽可能高的分辨率数据，并使用SAD/MAD位相方法对结构进行位相。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of our work is to define the structural basis of class-2 cytokine signaling. In this proposal, we seek define the structure of the receptor assembly that mediates IL-20 signaling. IL-20 forms a ternary complex with IL-20R1 and IL-20R2, which are cell surface receptors that signal through STAT3. At this time, no ternary receptor complexes have been reported for any class 2 cytokine. The biology of IL-20 suggests it mediates cross-talk between the immune and epithelial cells. Recent data suggests IL-20 is critical in the pathogenesis of Psoriasis and may be target to control the disease. Successful completion of the IL-20/IL-20R1/IL-20R2 complex will serve as the prototype 3-dimensional structure of a class 2 cytokine ternary complex and may be used to design novel therapies for Psoriasis. Crystals of the complex have been grown. Synchrotron radiation is needed to screen crystals, obtain the highest possible resolution data, and phase the structure using SAD/MAD phasing methods.