STRUCTURAL STUDY OF FCRY, AN AVIAN IGY TRANSCYTOSIS RECEPTOR

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。 对于哺乳动物来说，获得性免疫是通过一种名为FcRN的受体将IgG从母亲转移到幼崽身上实现的，FcRN在新生儿小肠中在酸性pH下与IgG结合，并在碱性pH下将其释放到血液中。FcRY是禽类FcRN的功能等价物，但属于包括磷脂酶A2受体在内的不同结构家族。FcRY与禽类免疫球蛋白IgY结合，并通过卵黄囊膜转移。结果表明，FcRY的胞外区在酸性和碱性pH之间有很大的构象变化，这与IgY的结合和释放相对应。然而，这种构象变化的结构细节尚不清楚。在这里，我们打算用SAXS来研究FcRY的构象变化及其与IgY的结合。这可能会提高我们目前对获得性免疫机制的了解，也可以提高我们对抗与禽类相关的人类疾病的策略。

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.