STRUCTURE OF POTASSIUM AND CHLORIDE CHANNELS

这个子项目是许多研究子项目中的一个 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， 因此可以在其他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。 钾离子通道和氯离子通道参与许多重要的生理过程，包括电信号的产生、渗透压控制以及激素和递质释放的信号传导。它们是许多药理学试剂的靶点，并且这些通道基因的突变与多种使人衰弱的疾病相关。离子通道的结构研究是一个较新的研究领域。我们已经解决了三个钾通道（KcsA，配体门控MthK通道，和最近公布的电压门控KvAP通道）和一个氯离子通道（ClC类）的结构。这些结构开始揭示了离子传导和通道门控（调节通道的打开和关闭）的基本原理。 我们目前的工作重点是离子通道门控的机制。MthK通道的结构首次揭示了钾通道配体门控的结构机制。研究内向整流钾通道胞质结构域和钙激活钾通道配体和非配体结构域的结构解，旨在深入了解不同配体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性门控的结构基础。KvAP通道的结构提供了对钾通道中电压依赖性门控如何工作的第一次一瞥。我们将继续研究电压门控的机制，通过解决不同构象的通道结构。ClC通道的门控与钾通道非常不同。

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.