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

IL-33 的结构及其与 ST2 和 IL-1RACP RE 的相互作用

• 批准号: 8362106
• 负责人: THOMAS F WEISS
• 金额: $ 0.14万
• 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/8362106
• 关键词: Asthma; Binding; Biochemical; Biological; CD4 Positive T Lymphocytes; Chemicals; Complex; Cytokine Receptors; Data; Disease; Effector Cell; Family; Family member; Funding; Grant; Helper-Inducer T-Lymphocyte; Host Defense; Hypersensitivity; Immune response; Immune system; Inflammatory; Interleukin-1; Interleukin-1 Receptors; Interleukins; Mediating; Modeling; Molecular; Molecular Models; National Center for Research Resources; Play; Principal Investigator; Radiation; Regulation; Research; Research Infrastructure; Resources; Role; Signal Transduction; Solutions; Source; Structure; Th2 Cells; United States National Institutes of Health; anakinra; cost; cytokine; interest; member; molecular modeling; receptor; response; structural biology

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. : 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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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。