INACTIVATION OF THE T CELL K+ CHANNEL

描述 该提案旨在确定相关的 C 失活机制 T 淋巴细胞中具有电压门控 K 通道。 该项目的第一个目标是 项目的目的是检验以下假设：亚基之间的相互作用 负责失活的四聚体通道是合作性的。 这个 假设将根据失活时间过程的变化进行评估 在由野生型组装的异源表达的异多聚体通道中 和具有不同化学计量的突变亚基。 最适合的 数学模型的数据将用于区分 不同的选择。 该研究的第二个目标旨在确定 亚基的哪些区域参与失活。 的 特别值得关注的是 S1-S2 环路的作用。 分子生物学 技术将用于该地区已被使用的快速通道 已修改。 表达电流和结构的数学建模 构象态之间转变的自由能分布将 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.