STRUCTURE OF POTASSIUM AND CHLORIDE CHANNELS

钾和氯离子通道的结构

• 批准号: 8170684
• 负责人: RODERICK MACKINNON
• 金额: $ 2.51万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170684
• 关键词: Chloride Channels; Computer Retrieval of Information on Scientific Projects Database; Cytoplasmic Tail; Disease; Funding; Genes; Grant; Hormones; Institution; Ion Channel; Ion Channel Gating; Ions; Ligands; Molecular Conformation; Mutation; Physiological Processes; Potassium Channel; Potassium Chloride; Production; Publishing; Research; Research Personnel; Resources; Signal Transduction; Solutions; Source; Structure; Time; United States National Institutes of Health; Work; base; insight; inward rectifier potassium channel; voltage

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 钾通道和氯化物通道有助于许多重要的生理过程，包括产生电信号，渗透控制以及激素和发射器的释放。它们是众多药理剂的靶标，这些通道基因的突变与多种使人衰弱的疾病有关。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的结构（KCSA，配体门控MTHK通道和最近发表的电压门控kVAP通道）和一个氯化物通道（CLC级）。这些结构开始揭示离子传导和通道门控的基本原理（通道的开放和关闭）。 我们当前的工作着重于离子通道门的机制。 MTHK通道的结构首次揭示了钾通道中配体门控的结构机制。在其配体和非配合形式中，向内整流钾通道的细胞质结构溶液和CA激活的钾通道的结构解决方案的项目，旨在更深入地了解不同配体podated钾通道中的基因机制。另一个大型正在进行的项目涉及钾通道中依赖电压门控的结构性基础。 KVAP通道的结构首先瞥见了钾通道中依赖电压的门控的作用。我们正在继续通过以不同构型解决通道的结构来研究电压门控机制。 CLC通道中的门控与钾通道大不相同。