MODELING HEPARIN INDUCED CONFORMATIONAL CHANGES IN INTERLEUKINE-5

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。 细胞因子IL-5可以模拟B细胞的生长，增加免疫球蛋白的分泌和嗜酸性粒细胞的激活。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，嗜酸性粒细胞造成的组织损伤最大。 库姆博士和她的合作者详细描述了IL-5与肝素的相互作用。还进行了对IL-5的定点突变分析。还对IL-5配体结合进行了一些初步的计算模拟。 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。我们的目标是了解在配体结合时蛋白质中可能带来的任何关键结构变化，以及这可能如何通过IL-5受体复合体影响IL-5信号。

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.