Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia.
Nature. 2018 Jul;559(7712):45-53. doi: 10.1038/s41586-018-0259-z. Epub 2018 Jul 4.
G-protein-coupled receptors (GPCRs) are key cell-surface proteins that transduce external environmental cues into biochemical signals across the membrane. GPCRs are intrinsically allosteric proteins; they interact via spatially distinct yet conformationally linked domains with both endogenous and exogenous proteins, nutrients, metabolites, hormones, small molecules and biological agents. Here we explore recent high-resolution structural studies, which are beginning to unravel the atomic details of allosteric transitions that govern GPCR biology, as well as highlighting how the wide diversity of druggable allosteric sites across these receptors present opportunities for developing new classes of therapeutics.
G 蛋白偶联受体（GPCRs）是一种关键的细胞膜表面蛋白，能够将外部环境线索转化为跨膜的生化信号。GPCRs 是固有变构蛋白；它们通过空间上不同但构象上相连的结构域与内源性和外源性蛋白质、营养素、代谢物、激素、小分子和生物制剂相互作用。在这里，我们探讨了最近的高分辨率结构研究，这些研究开始揭示控制 GPCR 生物学的变构转变的原子细节，并强调了这些受体中广泛的变构药物靶点多样性为开发新类别的治疗药物提供了机会。
