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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 白细胞介素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。它们通过与两个IL 1受体家族成员（初级受体和辅助受体）的细胞外结构域结合，形成异源三聚体信号传导全复合物，来激活效应细胞中的生物学应答。尽管IL 1细胞因子/受体复合物的重要性和长期的兴趣，只有IL 1b/IL 1受体I（IL 1 RI）和IL 1 Ra/IL 1 RI复合物已被表征的结构水平上的日期，信息的异源三聚体复合物的分子排列是不可用的。IL-33是近年来发现的一种IL-1样细胞因子，它参与了T辅助细胞2型介导的免疫应答，如哮喘或过敏。 我们使用小角度X射线散射结合NMR化学位移扰动数据和详细的生化表征，以获得溶液中IL-33/ST 2复合物的一致模型。该模型显示IL 33与ST 2形成类似于IL 1b/IL 1 RI复合物的复合物。我们将SAXS分析扩展到IL 33/ST 2/IL 1 RacP和IL 1b/IL 1 RI/IL 1 RacP复合物，并提出了IL 1三聚体信号复合物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.