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

冷冻电镜测定 G 蛋白偶联受体状态

• 批准号: DE230101681
• 负责人: Dr Xin Zhang
• 金额: $ 32.21万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: Discovery Early Career Researcher Award
• 财政年份: 2023
• 资助国家: 澳大利亚
• 起止时间: 2023-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/DE230101681
• 关键词: Cryo; electron; microscopy; determination; protein

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.

该项目旨在解决了解肽激素 G 蛋白偶联受体激活的分子机制方面的基本知识差距。这将通过冷冻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。新的生化方法将用于捕获这些状态，以胰高血糖素受体为例，胰高血糖素受体具有广泛的药理学工具，有助于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上重要的受体激活和功效的基本理解，而开发的方法将使对其他受体类别的类似研究成为可能。