Gating of ion channels and shutdown of G-protein-coupled receptors revealed by kinetic DEER spectroscopy.

动态 DEER 光谱揭示了离子通道的门控和 G 蛋白偶联受体的关闭。

• 批准号: 420322655
• 负责人: Professor Dr. Ulrich Benjamin Kaupp
• 金额: --
• 依托单位: Abteilung für Chemische Biologie
• 依托单位国家: 德国
• 项目类别: Reinhart Koselleck Projects
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/420322655?language=en
• 关键词: Gating; ion; channels; shutdown; protein

Membrane receptors (like G-protein-coupled receptors) and ion channels involved in cellular signaling become activated by binding of ligands. The structure of a few receptors and ion channels is known at molecular or atomic resolution. However, except for a few cases, the conformational changes during transition from one to another signaling state at Ångström and micro- to millisecond resolution are not known. I propose to use time-resolved pulsed electron paramagnetic resonance (EPR) techniques (PELDOR or DEER) to resolve these conformational changes in two different signaling processes: the opening of cyclic nucleotidesensitive ion channels and the shut-down of the visual pigment rhodopsin by the stop-protein arrestin. This approach has the potential to delineate the sequence of conformational changes in many signaling proteins and, thereby, serve as a model. The project is challenging and requires the cooperation of several experts in EPR spectroscopy, channel biophysics, protein chemistry, computational biophysics, and cellular signaling.

参与细胞信号传递的膜受体(如G蛋白偶联受体)和离子通道通过配体的结合而被激活。一些受体和离子通道的结构在分子或原子分辨率上是已知的。然而，除了少数情况外，从一种信令状态到另一种信令状态的转换过程中的构象变化以及微秒到毫秒的分辨率是未知的。我建议使用时间分辨脉冲电子顺磁共振(EPR)技术(PELDOR或DEER)在两个不同的信号过程中解决这些构象变化：打开环核苷酸敏感离子通道和停止蛋白arrestin关闭视觉色素视紫红质。这种方法有可能描绘出许多信号蛋白的构象变化序列，从而作为一个模型。该项目具有挑战性，需要EPR光谱学、通道生物物理学、蛋白质化学、计算生物物理学和细胞信号方面的几位专家的合作。