K CHANNEL DOMAIN STRUCTURES

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 第一个目标是继续研究真核生物和原核生物K通道膜外结构域的结构基础。我们最近对内向整流钾通道胞质调节结构域的研究将进一步扩展到包含其胞质调节蛋白如膜锚定蛋白PDZ结合结构域和小分子配体如PIP 2的复合物。已经产生了几种突变体的晶体来描述与通道门控相关的构象柔性的重要性（Pegan等人，2005年）。第二个目标是在不存在或存在不同去污剂的情况下获得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~3.2埃的衍射。 蛋白质将与其货物蛋白复合。对这些相关结构的系统分析将有助于理解Mistic分子协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.