STRUCTURE OF POTASSIUM AND CHLORIDE CHANNELS

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。 钾通道和氯通道参与许多重要的生理过程，包括电信号的产生、渗透调节、激素和递质的释放信号。它们是许多药理药物的靶标，这些通道基因的突变与各种衰弱疾病有关。离子通道的结构研究是一个相对较新的研究领域。我们已经解决了三个钾通道(KCSA、配体门控MthK通道和最近发表的电压门控KvAP通道)和一个氯通道(ClC类)的结构。这些结构开始揭示离子传导和通道门控(通道的调节打开和关闭)的基本原理。我们目前的工作主要集中在离子通道的门控机制上。MthK通道的结构首次揭示了钾通道中配体门控的结构机制。关于内向整流钾通道胞质结构域和钙激活钾通道配基和非配基形式的结构溶液的项目旨在更深入地了解不同配基门控钾通道的门控机制。另一个正在进行的大型项目涉及钾通道中电压依赖门控的结构基础。KvAP通道的结构首次揭示了钾通道的电压依赖性门控是如何起作用的。我们正在继续通过求解不同构象下的沟道结构来研究电压门控的机制。CLC通道的门控与钾通道有很大的不同。

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 and chloride channels contribute to many important physiological processes including the production of electrical signals, osmotic control, and signaling the release of hormones and transmitters. They are targets of numerous pharmacological agents, and mutations of these channel genes have been associated with a variety of debilitating diseases. The structural study of ion channels is a relatively new research field. We have solved the structures of three potassium channels (KcsA, the ligand gated MthK channel, and the recently published voltage gated KvAP channel) and of one chloride channel (ClC-class). These structures begin to reveal the fundamental principles of ion conduction and channel gating (the regulated opening and closing of the channel). Our current work focuses on mechanisms by which ion channels gate. The structure of the MthK channel revealed for the first time the structural mechanisms of ligand gating in potassium channels. Projects on the structure solution of cytoplasmic domains of inward rectifier potassium channels and of the Ca activated potassium channels in their liganded and unliganded form aim to gain deeper insight into the mechanisms of gating in different ligand gated potassium channels. Another large ongoing project concerns the structural basis of voltage dependent gating in potassium channels. The structure of the KvAP channel provided the first glimpse into how voltage dependent gating in Potassium channels works. We are continuing to investigate the mechanism of voltage gating by solving the structure of the channel in different conformations. Gating in ClC channels is very different from potassium channels.