Biological and Chemical Research Centre, University of Warsaw, ul. Żwirki i Wigury 101, Warsaw 02-089, Poland; Faculty of Life Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, United Kingdom.
Department of Neurology, University of Southern California, Los Angeles, CA 90089, United States.
Trends Biochem Sci. 2019 Apr;44(4):312-330. doi: 10.1016/j.tibs.2018.11.011. Epub 2019 Jan 3.
Many central biological events rely on protein-ligand interactions. The identification and characterization of protein-binding sites for ligands are crucial for the understanding of functions of both endogenous ligands and synthetic drug molecules. G protein-coupled receptors (GPCRs) typically detect extracellular signal molecules on the cell surface and transfer these chemical signals across the membrane, inducing downstream cellular responses via G proteins or β-arrestin. GPCRs mediate many central physiological processes, making them important targets for modern drug discovery. Here, we focus on the most recent breakthroughs in finding new binding sites and binding modes of GPCRs and their potentials for the development of new medicines.
许多重要的生物学事件依赖于蛋白质-配体相互作用。鉴定和描述配体的蛋白质结合部位对于理解内源性配体和合成药物分子的功能至关重要。G 蛋白偶联受体（GPCRs）通常在细胞表面检测细胞外信号分子，并将这些化学信号传递穿过细胞膜，通过 G 蛋白或β-arrestin 诱导下游细胞反应。GPCRs 介导许多重要的生理过程，使其成为现代药物发现的重要靶点。在这里，我们重点介绍了发现 GPCR 新的结合部位和结合模式的最新突破，以及它们在开发新药方面的潜力。
