STRUCTURAL STUDIES OF VOLTAGE-DEPENDENT K+ CHANNELS

该子项目是利用 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，不一定是研究者的机构。 钾通道将K+离子传导穿过细胞膜。钾传导介导广泛的细胞过程，包括细胞体积调节、激素分泌以及神经和肌肉细胞的电信号产生。我们专注于K+通道打开和关闭的机制，该过程称为门控，通过外部刺激，如细胞膜电压的变化。我们最近确定了真核电压依赖性K+通道的开放构象的结构。我们的目标是确定关闭状态的结构，以进一步了解膜电压如何控制这种通道的开放。此外，我们想确定各种配体的结构，包括毒素和电压传感器抑制剂，这将促进我们对电压依赖性钾通道药理学的理解。 我们还开发了G蛋白调节离子通道的晶体。电压门控通道和G蛋白调节通道将是我们同步辐射工作的重点。

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. Potassium channels conduct K+ ions across the membrane of cells. Potassium conduction mediates a wide range of cellular processes including cell volume regulation, hormone secretion, and electrical signal production by nerve and muscle cells. We are focused on the mechanisms by which K+ channels open and close, the process know as gating, by external stimuli such as changes in the cell membrane voltage. We have recently determined the structure of a eukaryotic voltage-dependent K+ channel in the open conformation. We aim to determine the structure of the closed state to further our understanding of how membrane voltage controls opening in this kind of channel. In addition, we would like to determine structures with various ligands including toxins and voltage sensor inhibitors that will advance our understanding of the pharmacology of voltage-dependent potassium channels. We also have developed crystals of a G-protein regulated ion channel. The voltage-gated channel and the G-protein regulated channel will be the main foci of our synchrotron work.