STRUCTURAL STUDY OF FCRY, AN AVIAN IGY TRANSCYTOSIS RECEPTOR

禽类IGY转细胞受体FCRY的结构研究

• 批准号: 8362373
• 负责人: Yongqun He
• 金额: $ 0.08万
• 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/8362373
• 关键词: Binding; Birds; Blood; Family; Funding; Grant; IgY; Immunoglobulin G; Mammals; Membrane; Mothers; National Center for Research Resources; Neonatal; Phospholipase A2; Principal Investigator; Radiation; Research; Research Infrastructure; Resources; Small Intestines; Source; United States National Institutes of Health; Yolk Sac; acquired immunity; cost; human disease; improved; neonatal Fc receptor; receptor; structural biology; transcytosis

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. For mammals, acquired immunity is achieved by transferring IgG from mother to young through a receptor called FcRn, which binds IgG at acidic pH in the neonatal small intestine and releases it at basic pH into blood. FcRY is an avian functional equivalent of FcRn, but belongs to a different structural family which includes phospholipase A2 receptor. FcRY binds IgY, the avian counterpart of IgG, and transfers it across yolk sac membranes. It has been shown that the ectodomain of FcRY has a large conformational change between acidic and basic pH which corresponds to the binding and the releasing of IgY. However, the structural details of this conformational change are unclear. Here we propose to use SAXS to investigate the conformational change of FcRY and its binding with IgY. This could improve our current understanding of the mechanisms of acquired immunity and also the strategies against avian- associated human diseases.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 对于哺乳动物，通过称为FCRN的受体将IgG从母亲转移到年轻人，该受体在新生儿小肠中结合IgG，并将其在基本的pH中释放到血液中，从而实现了获得的免疫力。 fcry是FCRN的鸟类功能，但属于包括磷脂酶A2受体的不同结构家族。 FCRY结合Igy，IgG的禽类对应物，并将其转移到蛋黄囊膜上。已经表明，fcry的胞外域在酸性和碱性pH之间具有较大的构象变化，这与Igy的结合和释放相对应。但是，这种构象变化的结构细节尚不清楚。在这里，我们建议使用SAXS研究FCRY的构象变化及其与IGY的结合。这可以提高我们目前对获得免疫机制以及针对禽类相关人类疾病的策略的理解。