STRUCTURAL STUDIES ON CYTOKINE-RECEPTOR COMPLEXES

细胞因子受体复合物的结构研究

• 批准号: 8362192
• 负责人: MARK R WALTER
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362192
• 关键词: Biology; Cell Surface Receptors; Complex; Cytokine Receptors; Cytokine Signaling; Data; Epithelial Cells; Funding; Goals; Grant; Immune; Mediating; Methods; National Center for Research Resources; Pathogenesis; Phase; Principal Investigator; Psoriasis; Radiation; Receptor Signaling; Reporting; Research; Research Infrastructure; Resolution; Resources; STAT3 gene; Signal Transduction; Source; Structure; Time; United States National Institutes of Health; Work; base; cost; cytokine; design; disorder control; interleukin 20; novel; prototype; receptor; structural biology; synchrotron radiation; three dimensional structure

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们工作的总体目标是确定2类细胞因子信号传导的结构基础。在这个提议中，我们试图定义介导IL-20信号传导的受体组装的结构。IL-20与IL-20 R1和IL-20 R2形成三元复合物，IL-20 R1和IL-20 R2是通过STAT 3发出信号的细胞表面受体。此时，尚未报道任何2类细胞因子的三元受体复合物。IL-20的生物学表明它介导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是至关重要的，并且可能是控制该病的靶点。IL-20/IL-20 R1/IL-20 R2复合物的成功完成将作为2类细胞因子三元复合物的原型三维结构，并可用于设计新的银屑病治疗方法。该复合物的晶体已经生长。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定相方法对结构进行定相。