THE STRUCTURE OF INTERLEUKIN-33 AND ITS INTERACTION WITH THE ST2 AND IL-1RACP RE

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。 白介素1(IL-1)家族的细胞因子在感染性和炎症性疾病的宿主防御和免疫系统调节中发挥重要作用。它们通过结合两个IL-1受体家族成员的胞外结构域，即主要受体和辅受体，激活效应细胞的生物反应，形成一个异源三聚体信号全息复合体。尽管IL-1细胞因子/受体复合体的重要性和长期的兴趣，但到目前为止，只有IL-1b/IL-1受体I(IL-1RI)和IL-1ra/IL-1RI复合体在结构水平上被表征；关于异源三聚体复合体的分子排列的信息尚不清楚。IL-33是新近发现的一种类似IL-1的细胞因子，参与T辅助细胞2型介导的免疫反应，如哮喘、过敏等。我们使用小角X射线散射，结合核磁共振化学位移微扰数据和详细的生化表征，获得了IL-33/ST2复合物在溶液中的一致模型。模型显示，IL-33与ST2形成类似于IL-1b/IL-1RI的复合体。我们将我们的SAXS分析扩展到IL-33/ST2/IL-1racP和IL-1b/IL-1RI/IL-1racP复合体，并提出了IL-1三聚体信号复合体分子排列的一般模型。

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. : Members of the interleukin 1 (IL 1) family of cytokines play major roles in host defense and immune system regulation in infectious and inflammatory diseases. They activate the biological response in effector cells by binding to the extra cellular domain of two IL 1 receptor family members, the primary receptor and the co receptor, forming a heterotrimeric signaling holocomplex. Despite the importance and the long interest in IL 1 cytokine/receptor complexes, only the IL 1b/IL 1 receptor I (IL 1 RI) and IL 1Ra/IL 1 RI complexes have been characterized on a structural level to date; information on the molecular arrangement of the heterotrimeric complexes is not available. Il-33 is a recently discovered IL-1 like cytokine, which was shown to be involved in T-helper-cell type 2 mediated immune responses, such as asthma or allergy. We used small angle x-ray scattering in combination with NMR chemical shift perturbation data and detailed biochemical characterization to obtain a consistent model of the IL-33/ST2 complex in solution. The model shows that IL 33 forms a complex with ST2 that is similar to the IL 1b/IL 1 RI complex. We extended our SAXS analysis to the IL 33/ST2/IL 1RacP and IL 1b/IL 1 RI/IL 1RacP complexes and propose a general model of the molecular arrangement of the IL 1 trimeric signaling complexes.