Calmodulation of Auditory Potassium Channels

描述（由申请人提供）：钙调素蛋白对于听觉KCNQ通道的组装和调节至关重要。 尽管与源自离子通道的肽片段结合的钙调素有许多信息丰富的高分辨率结构，但对于所有离子通道来说，钙调素在功能通道上的位置以及钙诱导的负责生理功能的结构变化仍然难以捉摸。 该提案概述了一种创新的新方法，检测KCNQ结合的钙调素及其与离子传导途径的距离。 使用这些实验确定的距离限制和许多高分辨率的结构钾通道和钙调蛋白结合肽，我们将产生四级结构的不同钙化KCNQ 4和KCNQ 1/KCNE 1-钙调蛋白复合物。 这些四级结构与拟议的功能研究相结合，将提供前所未有的分子洞察钙调节钾循环在耳朵。

DESCRIPTION (provided by applicant): Calmodulin proteins are vital for both the assembly and regulation of auditory KCNQ channels. Although there are many informative high resolution structures of calmodulin bound to peptide fragments derived from ion channels, the location of calmodulin on functioning channels and the calcium-induced structural changes responsible for physiological function have remained elusive for all ion channels. This proposal outlines an innovative new approach that detects KCNQ-bound calmodulin and its distance from the ion conduction pathway. Using these experimentally determined distance restraints and the many high resolution structures of potassium channels and calmodulin bound to peptides, we will generate quaternary structures of the differently calcified KCNQ4- and KCNQ1/KCNE1-calmodulin complexes. These quaternary structures combined with the proposed functional studies will provide unprecedented molecular insight into calcium-regulated potassium recycling in the ear.