Structural Studies on Prokaryotic Potassium Channels

原核生物钾通道的结构研究

• 批准号: 6967305
• 负责人: Adrian Gross
• 金额: $ 27.83万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967305
• 关键词: Streptomyces; X ray crystallography; electron spin resonance spectroscopy; electrophysiology; lipid bilayer membrane; membrane model; membrane potentials; molecular cloning; potassium channel; prokaryote; protein folding; protein structure function; voltage gated channel

DESCRIPTION (provided by applicant): Ion channels are instrumental in the generation of membrane potential, receptor potential, and action potential. They are the molecular building blocks for what is an essential characteristic of many cells in neuroscience: excitability. These proteins are implicated in the physiology and pathophysiology of all excitable tissues, underlie many disease processes including epilepsies and arrhythmias, and are major targets of essential drugs used in clinical medicine. Potassium channels are the phylogenetic founders of a large superfamily of structurally related ion channels that includes nucleotide gated channels, sodium channels, and calcium channels. Potassium channels are typically assembled from four identical subunits in a four-fold symmetrical fashion. This rather simple structural blueprint and the substantial practical advantage of only one subunit type have made potassium channels a much studied model system. Potassium channels exhibit two important properties: they selectively admit potassium over sodium and they change their structure during function in a process called gating. This proposal explores the gating transition in potassium channels. We will use a combination of cysteine scanning mutagenesis, site-directed spin labeling, site-directed mass tagging, X-ray crystallography, and electrophysiology to study the gating transition in three prokaryotic potassium channels: KcsA, MthK, and KvAP. The long term goal of this proposal is to understand functional properties of ion channels at a structural level.

描述（由申请人提供）：离子通道有助于产生膜电位，受体电位和动作电位。它们是许多细胞在神经科学中的基本特征的分子构建块：兴奋性。这些蛋白质与所有令人兴奋的组织的生理和病理生理学有关，这是许多疾病过程，包括癫痫和心律不齐，是临床医学中使用的必需药物的主要靶标。钾通道是包括核苷酸门控通道，钠通道和钙通道的大型超家族的系统发育创始人。钾通道通常以四倍的对称方式从四个相同的亚基组装。这种相当简单的结构蓝图和只有一种亚基类型的实质性实践优势使钾通道成为了众所周知的模型系统。钾通道具有两种重要特性：它们有选择地将钾在钠上允许，并在称为门口的过程中改变其在功能过程中的结构。该建议探讨了钾通道中的门控过渡。我们将结合半胱氨酸扫描诱变，位于位置定向的自旋标记，定位的质量标记，X射线晶体学和电生理学来研究三个原核生物钾通道的门控转变：KCSA，MTHK和KVAP。 该建议的长期目标是了解结构层面离子通道的功能特性。