INACTIVATION OF THE T CELL K+ CHANNEL

描述 该提案旨在确定与C-失活相关的机制， 与T淋巴细胞中的电压门控K通道有关。 第一个目标 项目是测试假设，亚单位之间的相互作用 负责失活的四聚体通道是协同的。 这 将根据灭活时程的变化对假设进行评价 在从野生型组装的异源表达的异源多聚体通道中， 和具有不同定义的化学计量的突变亚基。 最适合的 数学模型的数据将被用来区分 不同的选择 本研究的第二个目的是确定 亚基的哪些区域参与失活。 的 特别关注的是S1-S2循环的作用。 分子生物学 技术将用于表达渠道，其中该地区已被 修改. 表达电流和结构的数学建模 构象状态之间转换的自由能分布将 导致对该区域在C-失活中作用的描述。

DESCRIPTION This proposal seeks to determine the mechanism of C-inactivation associated with voltage-gated K channels in T-lymphocytes. The first aim of the project is to test the hypothesis that interactions among the subunits of the tetrameric channel responsible for inactivation is cooperative. This hypothesis will be evaluated from changes in the time course of inactivation in heterologous expressed heteromultimeric channels assembled from wild-type and mutant subunits with different defined stoichiometries. Best fits of the data to mathematical models will be used to distinguish between different alternatives. The second aim of the study seeks to determine which regions of the subunits participate in the inactivation. Of particular focus is the role of the S1-S2 loop. Molecular biology techniques will be used express channels in which this region has been modified. Mathematical modeling of the expressed current and construction of free energy profiles for transitions between conformational states will lead to a description of a role for this region in C-inactivation.