INTERLEUKIN-5 RECEPTOR IN COMPLEX WITH INTERLEUKIN-5

与 INTERLEUKIN-5 复合的 INTERLEUKIN-5 受体

• 批准号: 7358880
• 负责人: Patrick J Loll
• 金额: $ 0.36万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7358880
• 关键词: INTERLEUKIN; RECEPTOR; COMPLEX

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. Interleukin 5 (IL5) is the major hematopoietic cytokine responsible for differentiation, proliferation, migration, and activation of eosinophils. Eosinophils play key roles in the innate immune response and are also important players in pathological states such as asthma. IL5 acts on eosinophils through a cell surface receptor that contains alpha and beta chains, with alpha being primarily responsible for ligand binding and beta for signal transduction. As a first step in understanding how IL5 recruits alpha and beta chains and assembles them into a complex competent for intracellular signaling, we have crystallized the complex of IL5 with the extracellular domain of the receptor alpha chain. Our collaborators in the Chaiken laboratory have many years of experience in studying IL5-receptor interactions, and our structure will prove extremely useful in evaluating the data they have amassed concerning the development of agonists and antagonists and the effects of mutagenesis. Our long term goals include the crystallization of the IL5-alpha-beta complex, crystallization of the receptor with various peptide agonists and antagonists, and correlation of our structural results with functional data on receptor assembly acquired by the Chaiken group. A thorough structural and mechanistic understanding of how receptor assembly proceeds and leads to signaling will prove useful in the development of therapeutics for allergic inflammations such as asthma.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。白介素5(IL5)是主要的造血细胞因子，负责嗜酸性粒细胞的分化、增殖、迁移和激活。嗜酸性粒细胞在先天免疫反应中发挥关键作用，也是哮喘等病理状态的重要参与者。IL5通过含有α链和β链的细胞表面受体作用于嗜酸性粒细胞，α链主要负责配体结合，β链负责信号转导。作为理解IL5如何招募α和β链并将它们组装成能够进行细胞内信号传递的复合体的第一步，我们已经将IL5的复合体与受体阿尔法链的胞外结构域结晶。我们在Chaiken实验室的合作者在研究IL5-受体相互作用方面有多年的经验，我们的结构将被证明在评估他们积累的关于激动剂和拮抗剂的开发以及突变的影响的数据方面非常有用。我们的长期目标包括IL5-α-β复合体的结晶，受体与各种多肽激动剂和拮抗剂的结晶，以及我们的结构结果与柴肯小组获得的受体组装功能数据的相关性。彻底了解受体组装如何进行并导致信号传递的结构和机制将被证明有助于开发治疗哮喘等过敏性炎症的药物。