STRUCTURE OF THE ZINC TRANSPORTER YIIP

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 锌转运蛋白在调节细胞锌稳态中起着核心作用。金属离子的运输被认为是金属离子沿一个或多个结合部位的平衡结合和带电运动的综合过程。我们的长期目标是了解锌转运蛋白中与金属离子结合和移动相关的潜在分子事件的结构基础。这项拟议的研究将集中在锌外排泵的一个主要家族-阳离子扩散促进剂(CDF)。我们将探索结合特性和金属离子迁移率是如何被构建到具有代表性的CDF转运蛋白YIIP的结构中的。为此，我们将(1)过度表达、提纯和结晶YIP；(2)使用可以衍射到高分辨率的晶体来确定YIP的结构。这项研究代表了CDF在分子水平上的第一系列结构-功能分析。解决具有代表性的CDF的结构将为基于结构的药物设计奠定基础，目标是到目前为止已确定的七个人CDF(ZnT1-7)。

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. Zinc transporters play a central role in regulating cellular zinc homeostasis. The transport of metal ions is thought to be a combined process of equilibrium binding and energized movement of metal ions along one or more binding sites in a translocation pathway across the membrane. Our long-term goal is to understand the structural basis underlying molecular events associated with the binding and movement of metal ions in zinc transporters. This proposed study will focus on a major family of zinc efflux pumps, the cation diffusion facilitators (CDFs). We will explore how the binding property and metal ion mobility are built into the structure of YiiP, a representative CDF transporter from E. coli. Toward these ends, we will (1) over-express, purify and crystallize YiiP; (2) determine YiiP structures using crystals that can diffract to high resolutions. This study represents the first series of structure-function analyses of a CDF at a molecular level. Solving the structure of a representative CDF will set the stage for structure-based drug design targeting seven human CDFs (ZnT1-7) identified thus far.