School of Pharmacy, Sungkyunkwan University, 2066 Seoburo, Jangan-gu, Suwon, 16419, Republic of Korea.
School of Pharmacy, Sungkyunkwan University, 2066 Seoburo, Jangan-gu, Suwon, 16419, Republic of Korea.
Curr Opin Struct Biol. 2021 Aug;69:117-123. doi: 10.1016/j.sbi.2021.03.013. Epub 2021 May 8.
The precise structural mechanism of G protein-coupled receptor (GPCR)-G protein coupling has been of significant research interest because it provides fundamental knowledge on cellular signaling and valuable information for GPCR-targeted drug development. Over the last decade, several GPCR-G protein complex structures have been identified. However, these structures are mere snapshots of guanosine diphosphate (GDP)-released stable GPCR-G protein complexes, which have limited the understanding of the allosteric conformational transition during receptor binding to GDP release and the GPCR-G protein coupling selectivity. Recently, deeper insights into the mechanism underlying stepwise conformational changes during GPCR-G protein coupling were obtained using hydrogen/deuterium exchange mass spectrometry, hydroxyl radical footprinting-mass spectrometry, X-ray crystallography, cryoelectron microscopy, and molecular dynamics simulation techniques. This review summarizes these recent developments.
G 蛋白偶联受体（GPCR）-G 蛋白偶联的确切结构机制一直是研究的重点，因为它为细胞信号转导提供了基础知识，也为 GPCR 靶向药物的开发提供了有价值的信息。在过去的十年中，已经确定了几种 GPCR-G 蛋白复合物的结构。然而，这些结构仅仅是 GDP 释放的稳定 GPCR-G 蛋白复合物的快照，这限制了对受体结合到 GDP 释放过程中变构构象转变以及 GPCR-G 蛋白偶联选择性的理解。最近，使用氢/氘交换质谱、羟基自由基足迹质谱、X 射线晶体学、低温电子显微镜和分子动力学模拟技术，对 GPCR-G 蛋白偶联过程中逐步构象变化的机制有了更深入的了解。本文综述了这些最新进展。
