MODELING HEPARIN INDUCED CONFORMATIONAL CHANGES IN INTERLEUKINE-5

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且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。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 细胞因子 IL-5 的作用是模拟 B 细胞生长，增加免疫球蛋白分泌和嗜酸性粒细胞活化。它在哮喘和过敏性鼻炎等过敏性疾病中发挥着关键作用，在这些疾病中，嗜酸性粒细胞会造成最大的组织损伤。 Coombe 博士和她的合作者详细描述了 IL-5 与肝素的相互作用。还对 IL-5 进行了定点诱变分析。 IL-5 配体结合的一些初步计算模型也已完成。 我们将使用自动对接和分子动力学模拟来表征 IL-5 与肝素的相互作用。目标是了解配体结合后蛋白质可能发生的任何关键结构变化，以及这如何通过 IL-5 受体复合物影响 IL-5 信号传导。

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. Cytokine IL-5 functions to simulate B cell growth increase immunoglobulin secretion and eosinophil activation. It holds a key role in allergic diseases such as asthma and allergic rhinitis where eosinophils cause the maximum tissue damage. Dr. Coombe and her collaborators have characterized the interaction of IL-5 with heparin in detail. Site directed mutagenesis analyses on IL-5 have also been performed. Some initial computational modeling of IL-5 ligand binding has been performed too. We will be using automated docking and molecular dynamics simulations to characterize the interaction of IL-5 with heparin. The goal is to understand any key structural changes that might be brought about in the protein upon ligand binding and how that may affect IL-5 signaling via the IL-5 receptor complex.