STRUCTURE OF THE ZINC TRANSPORTER YIIP

锌转运蛋白YIIP的结构

• 批准号: 7726266
• 负责人: Dax Fu
• 金额: $ 2.2万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-18 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726266
• 关键词: Binding; Binding Sites; Cations; Computer Retrieval of Information on Scientific Projects Database; Diffusion; Drug Design; Equilibrium; Escherichia coli; Event; Family; Funding; Goals; Grant; Homeostasis; Human; Institution; Ions; Membrane; Metals; Molecular; Movement; Pathway interactions; Play; Process; Property; Research; Research Personnel; Resolution; Resources; Role; Series; Source; Staging; Structure; Thinking; United States National Institutes of Health; Zinc; base; efflux pump; ion mobility; zinc-binding protein

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 锌转运蛋白在调节细胞锌稳态中发挥着核心作用。 金属离子的转运被认为是金属离子沿着跨膜易位途径中的一个或多个结合位点的平衡结合和通电运动的组合过程。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。这项拟议的研究将重点关注锌外排泵的一个主要系列，即阳离子扩散促进剂（CDF）。 我们将探讨如何将结合特性和金属离子迁移率构建到 YiiP（大肠杆菌的代表性 CDF 转运蛋白）的结构中。为了实现这些目标，我们将（1）过度表达、纯化和结晶YiiP； (2) 使用可衍射至高分辨率的晶体确定 YiiP 结构。这项研究代表了 CDF 在分子水平上的结构功能分析的第一系列。解决代表性 CDF 的结构将为针对迄今为止确定的七种人类 CDF (ZnT1-7) 的基于结构的药物设计奠定基础。