K CHANNEL DOMAIN STRUCTURES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 第一个目标是继续研究真核和原核生物K通道膜外域的结构基础。我们最近在内向整流K通道的细胞质调节域方面的工作将进一步扩展包含其细胞质调节蛋白的复合体，如膜锚定蛋白的PDZ结合结构域和小分子配体如PIP2。已经产生了几个突变体的晶体来描述与通道门控相关的构象灵活性的重要性(Pegan等人，2005年)。第二个目标是在没有或存在不同洗涤剂的情况下获得Mistic和Mistic变体的高分辨率结构。我们命名为M2的Mistic的一个这样的变体已经结晶，并显示出约3.2埃的衍射。这种蛋白质将与其货运蛋白形成络合。对这些相关结构的系统分析将有助于理解Mistic在帮助蛋白质整合到疏水膜中的作用机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The first goal is to continue investigating the structural basis of the extramembraneous domains of K channels from eukaryotes and prokaryotes. Our recent work of cytoplasmic regulatory domain of inwardly rectifying K channels will be further expanded complexes containing its cytoplasmic regulatory proteins such as PDZ-binding domain of membrane anchoring proteins and small-molecule ligands such as PIP2. Crystals of several mutants have been generated to delineate the significance of conformational flexibility in association with channel gating (Pegan et al., 2005). The second goal is to obtain the high-resolution structure of Mistic and Mistic variants in the absence or presence of different detergents. One such variant of Mistic we named M2 has been crystallized and shows diffraction to ~3.2 Angstrom. The protein will be complexed by its cargo proteins. Systematic analyses of these related structures will help understanding the action mechanism of Mistic in assisting protein integration into hydrophobic membrane.