ION CHANNEL STRUCTURE AND FLUORESCENCE ENERGY TRANSFFER

描述（改编自申请人的摘要）：检查关系 电压门控离子通道的结构和功能之间的联系不仅 阐明细胞兴奋性的基本机制，但也将 解释离子通道是如何失灵的 离子通道突变已经被 与从代谢紊乱到心脏病等疾病有关 心律失常，可能与癫痫和其他神经系统疾病有关。 紊乱 了解电压敏感性的分子机制， 离子通道不仅可以更好地理解电 神经元之间的通信，但也将有助于解释临床 离子通道紊乱的表现。 当前对电压门控 离子通道表明通道的不同区域经历了 构象随电压变化。 然而，这些规模 变化及其对通道结构的影响是未知的， 蛋白质的三级结构 测量不同物体之间的距离 作为电压函数的沟道区域将有助于阐明 与电压门控相关的构象变化。 荧光 共振能量转移（FRET）已被用来测量距离 两种不同的荧光探针供体分子和受体之间 分子，通过测量探针之间的能量转移。 通过 将一个探针连接到假定的电压敏感区，另一个连接到 在通道的静态区域，FRET有可能确定哪个 通道的区域响应于电压和距离而移动 通过这些区域从通道的关闭状态行进到通道的打开状态。

DESCRIPTION (Adapted from applicant's abstract): Examining the relationship between structure and function in voltage-gated ion channels will not only clarify the fundamental mechanisms of cellular excitability, but will also explain how ion channels can malfunction. Ion channel mutations have been linked to disorders ranging from metabolic disturbances to heart arrhythmias, with possible links to epilepsy and other neurological disorders. Understanding the molecular mechanisms of voltage sensitivity in ion channels will not only lead to a better understanding of the electrical communication between neurons, but will also help explain the clinical manifestations of ion channel disorders. Current knowledge of voltage-gated ion channels indicates that different regions of the channel undergo conformational changes with voltage. However, the magnitude of these changes and their effects on channel structure are unknown, as is the tertiary structure of the protein. Measuring distances between different regions of the channel as a function of voltage will help elucidate the conformational changes associated with voltage gating. Fluorescence resonance energy transfer (FRET) has been used to measure the distance between two different fluorescent probes, a donor molecule and an acceptor molecule, by measuring the transfer of energy between the probes. By attaching one probe to a putative voltage-sensing region and the other to a static region of the channel, FRET has the potential to determine which regions of the channel move in response to voltage and the distances traveled by these regions from the closed to the open state of the channel.