STRUCTUAL STUDIES OF POTASSIUM CHANNEL INTRACELLULAR DOMAINS AND ASSOC SUBUNITS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。电压依赖性钾离子通道（Kv）根据膜电位的变化控制钾离子通过细胞膜的流动。千伏通道是许多基本生物过程的中心，如神经传导、肌肉收缩和激素分泌。我们在原子水平上研究了通道调制的分子机制。KCNQ是Kv频道家族的成员。它有一个大的c端结构域，这个结构域内的突变会引起心律失常和癫痫发作。我们已经结晶了c端结构域。晶体很小，在家用探测器上的初步测试表明，它的衍射到~15埃。我们目前正在完善结晶条件。Kv - β是附着在Kv通道上的细胞内蛋白。我们已经在复杂的通道域中获得了kvβ晶体，并且具有调节通道功能的小分子。晶体在母源处衍射至~3A。CHESS的高强度光束将使我们能够筛选晶体并获得小晶体的高分辨率数据集。这些实验只需要单色光束。

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. Voltage-dependent potassium channels (Kv) control the flow of K+ through the cell membrane in response to changes in membrane potential. Kv channels are central to many fundamental biological processes, such as nerve conduction, muscle contraction, and hormone secretion. We study the molecular mechanism of channel modulation at the atomic level. KCNQ is member of the Kv channel family. It has a large C-terminus domain and mutations within this domain causes arrythmias and seizure. We have crystallized the C-terminus domain. The crystals are small and initial tests on home detectors show that it diffracts to ~15 angstrom. We are currently refining the crystallization conditions. Kvbeta is an intracellular protein attached to a Kv channel. We have obtained Kvbeta crytals in complex a channel domain, and with small molecules that regulate channel function. The crystals diffract to ~3A at home source. The high intensity beam at CHESS will enable us to screen crystals and obtain high resolution data set on small crystals. We will only need monochromatic beam for these experiments.