Cryo-electron microscopy determination of G protein-coupled receptor states

该项目旨在解决基本知识的差距，了解肽激素G蛋白偶联受体激活的分子机制。这将通过低温电子显微镜确定激活过程中关键中间态的结构和动力学来实现。新的生物化学方法将被应用于捕获这些状态，使用胰高血糖素受体作为示例，其具有广泛的药理学工具以促进分离不同的功能状态。从这些研究中获得的知识将促进对生理学上重要的受体活化和功效的基本理解，而开发的方法将使其他受体类别的类似研究成为可能。

This project aims to address fundamental knowledge gaps in understanding of the molecular mechanisms of peptide hormone G protein-coupled receptor activation. This will be achieved through cryo-electron microscopy determination of the structure and dynamics of key intermediate states in activation. Novel biochemical approaches will be applied to capture these states, using as exemplar the glucagon receptor that has a broad range of pharmacological tools to facilitate isolation of distinct functional states. The knowledge gained from these studies will advance fundamental understanding of physiologically important receptor activation and efficacy, while the approaches developed will enable similar investigation of other receptor classes.