INACTIVATION OF THE T CELL K+ CHANNEL

描述 这项建议试图确定与C失活相关的机制 T淋巴细胞上存在电压门控性K通道。的第一个目标是 该项目是测试假设之间的相互作用的亚单位 负责失活的四聚体通道是协同的。这 假说将根据失活时间进程的变化进行评估 在野生型组装的异源表达的异多聚体通道中 以及具有不同定义化学计量的突变亚基。最适合的 将数据转换为数学模型将被用来区分 不同的选择。这项研究的第二个目标试图确定 亚基的哪些区域参与失活。的 特别关注的是S1-S2环路的作用。分子生物学 技术将使用快递通道，这一地区已经 修改过的。表达的电流和结构的数学模型 构象状态之间的跃迁的自由能分布将 导致对该区域在C失活中的作用的描述。

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.