STRUCTURAL STUDIES OF POTASSIUM TRANSPORTERS AND POTASSIUM CHANNELS

钾转运蛋白和钾通道的结构研究

• 批准号: 8363371
• 负责人: MING ZHOU
• 金额: $ 1.03万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363371
• 关键词: Address; Affect; Cell membrane; Complex; Crystallography; Escherichia coli; Funding; Goals; Grant; Human; Integral Membrane Protein; Iodides; Ion Transport; Ions; Light; Membrane; Membrane Potentials; National Center for Research Resources; Physiology; Play; Potassium; Potassium Channel; Principal Investigator; Research; Research Infrastructure; Resolution; Resources; Role; Sodium; Source; Structure; Synchrotrons; Thyroid Gland; TrkA protein; United States National Institutes of Health; Work; cost; response; small molecule; sodium-iodide symporter; symporter; voltage

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. Ion symporters are integral membrane proteins that co-transport two different ion species across the membrane. They play important roles in human physiology: the Sodium/Iodide symporter, for example, is responsible for accumulation of iodide in the thyroid gland. However, an atomic level mechanistic understanding of how symporters work is lacking. The long term goal of the first project is to obtain high resolution structures of an E. coli Sodium/Potassium symporter, TrkH, in complex with a regulatory intracellular protein, TrkA. We will address the questions of how the ion selectivity is achieved, and how the function of ion transport is regulated by intracellular ATP level.Voltage-dependent potassium channels (Kv) control the flow of K+ through the cell membrane in response to changes in membrane potential. The long-term goal of the second project is to develop an atomic level understanding of channel modulation mechanisms. In this project, we focus on modulation of Kv channel by beta subunit. We will solve high resolution structures of the beta subunit in complex with intracellular channel domains, in reduced and in oxidized forms. We will also solve structure of the beta subunit in complex with small molecule modulators that affect channel functions.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 离子共转运蛋白是整合的膜蛋白，其跨膜共转运两种不同的离子种类。它们在人体生理学中起着重要作用：例如，钠/碘同向转运体负责甲状腺中碘的积累。然而，缺乏对协同转运体如何工作的原子水平的机械理解。第一个项目的长期目标是获得高分辨率的E。大肠杆菌钠/钾同向转运体TrkH与细胞内调节蛋白TrkA复合。我们将讨论离子选择性是如何实现的，以及离子转运功能是如何受细胞内ATP水平的调节。电压依赖性钾通道（Kv）响应膜电位的变化控制K+通过细胞膜的流动。第二个项目的长期目标是发展对通道调制机制的原子水平理解。在本项目中，我们主要研究β亚基对Kv通道的调节。 我们将解决高分辨率结构的β亚基在复杂的细胞内通道结构域，在还原和氧化的形式。我们还将解决与影响通道功能的小分子调节剂复合的β亚基的结构。