STRUCTURE OF THE ZINC TRANSPORTER YIIP

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 锌转运蛋白在调节细胞锌稳态中起着重要作用。 金属离子的转运被认为是平衡结合和金属离子沿着跨膜易位途径中的一个或多个结合位点的能量化运动的组合过程。我们的长期目标是了解与锌转运蛋白中金属离子的结合和运动相关的分子事件的结构基础。这项拟议的研究将集中在一个主要的家庭锌外排泵，阳离子扩散促进剂（CDF）。 我们将探索结合性质和金属离子迁移率如何构建到YiiP的结构中，YiiP是来自E.杆菌为了这些目的，我们将（1）过表达，纯化和结晶YiiP;（2）确定YiiP结构使用晶体，可以重现高分辨率。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。解决一个代表性的CDF的结构将为基于结构的药物设计奠定基础，目标是迄今为止确定的七个人类CDF（ZnT 1 -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.