STRUCTURAL STUDIES OF POTASSIUM TRANSPORTERS AND POTASSIUM CHANNELS

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。 离子转运体是一种完整的膜蛋白，它共同运输两种不同的离子物种穿过膜。它们在人体生理中扮演着重要的角色：例如，钠/碘同向转运体负责在甲状腺中积累碘。然而，缺乏对符号如何工作的原子层面的机械理解。第一个项目的长期目标是获得大肠杆菌钠/钾转运蛋白TrkH与调节细胞内蛋白TrkA的复合体的高分辨率结构。我们将讨论离子选择性是如何实现的，以及细胞内ATP水平是如何调节离子转运功能的。电压依赖性钾通道(Kv)控制K+通过细胞膜的流动，以响应膜电位的变化。第二个项目的长期目标是发展对信道调制机制的原子水平的理解。在本项目中，我们主要研究β亚基对Kv通道的调制作用。我们将解决具有细胞内通道结构域的复合体中β亚基的高分辨率结构，包括还原和氧化形式。我们还将解决与小分子调节剂的复合体中影响通道功能的β亚基的结构。

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.