Structural Studies on Prokaryotic Potassium Channels

原核生物钾通道的结构研究

基本信息

批准号：
7924176
负责人：
Adrian Gross
金额：
$ 10.63万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7924176
关键词：
Action Potentials Address Amino Acid Sequence Arrhythmia Binding Biological Models Calcium Channel Cells Characteristics Clinical Medicine Complex Consensus Crystallization Cysteine DNA Sequence Rearrangement Disease Drug usage Educational process of instructing Electron Spin Resonance Spectroscopy Electrons Electrophysiology (science)Epilepsy Essential Drugs Exhibits Functional disorder Generations Goals Immunoglobulin Fragments Ion Channel Ion Channel Gating Laboratories Lipid Bilayers Mass Spectrum Analysis Membrane Potentials Membrane Proteins Molecular Molecular Conformation Neuraxis Neurosciences Nucleotides Phylogenetic Analysis Physiologic pulse Physiological Physiology Potassium Potassium Channel Process Property Protein Dynamics Proteins Research Research Personnel Resolution Scanning Seminal Signal Transduction Site Site-Directed Mutagenesis Sodium Sodium Channel Spin Labels Structure Study models Techniques Tetraethylammonium Time Tissues Uncertainty Work X-Ray Crystallography base improved insight interest prokaryotic potassium channel receptor voltage

项目摘要

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）：离子通道有助于膜电位、受体电位和动作电位的产生。它们是神经科学中许多细胞的基本特征：兴奋性的分子构建块。这些蛋白质与所有兴奋组织的生理学和病理生理学有关，是包括癫痫和心律失常在内的许多疾病过程的基础，并且是临床医学中使用的基本药物的主要靶标。钾通道是结构相关离子通道大家族的系统发育奠基者，其中包括核苷酸门控通道、钠通道和钙通道。钾通道通常由四个相同的亚基以四重对称的方式组装而成。这种相当简单的结构蓝图和仅一种亚基类型的巨大实际优势使钾通道成为备受研究的模型系统。钾通道表现出两个重要的特性：它们选择性地接纳钾而不是钠，并且在功能过程中通过称为门控的过程改变其结构。该提案探讨了钾通道的门控转变。我们将结合使用半胱氨酸扫描诱变、定点自旋标记、定点质量标记、X 射线晶体学和电生理学来研究三种原核钾通道的门控转变：KcsA、MthK 和 KvAP。该提案的长期目标是在结构水平上了解离子通道的功能特性。