MODELING HEPARIN INDUCED CONFORMATIONAL CHANGES IN INTERLEUKINE-5

模拟肝素诱导的 INTERLEUKINE-5 构象变化

• 批准号: 8361859
• 负责人: ROBERT J WOODS
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361859
• 关键词: Affect; Allergic Disease; Allergic rhinitis; Asthma; B-Lymphocytes; Complex; Computer Simulation; Docking; Funding; Goals; Grant; Heparin; Immunoglobulins; Interleukin-5; Ligand Binding; Modeling; National Center for Research Resources; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Signal Transduction; Simulate; Site-Directed Mutagenesis; Source; Tissues; United States National Institutes of Health; cell growth; cost; cytokine; eosinophil; molecular dynamics; receptor

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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 细胞因子IL-5的功能是刺激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，其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。也进行了IL-5配体结合的一些初始计算建模。 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。目的是了解配体结合后可能在蛋白质中引起的任何关键结构变化，以及如何通过IL-5受体复合物影响IL-5信号传导。