iHuman Institute, ShanghaiTech University, 2F Building 6, 99 Haike Road, Pudong New District, Shanghai, 201210, China.
iHuman Institute, ShanghaiTech University, 2F Building 6, 99 Haike Road, Pudong New District, Shanghai, 201210, China.
Trends Biochem Sci. 2015 Feb;40(2):79-87. doi: 10.1016/j.tibs.2014.12.005. Epub 2015 Jan 15.
Traditionally, G protein-coupled receptor (GPCR) activity has been characterized by ligand properties including affinity (Ki), potency (IC50/EC50), efficacy (Emax), and kinetics (Kon/Koff). These properties are related to ligand residence time, a general index of drug-target interaction in vivo. Recent GPCR structure-function breakthroughs have all required ligand stabilization of the receptor in some manner, highlighting the natural instability of these important cell surface receptors. This research has initiated a new era of discovery that highlights the importance of ligand-receptor interactions beyond the traditional mindset. We propose that receptor stability is related to receptor folding and residence in the cell membrane, affording a new dimension that should be considered when studying receptor function.
传统上，G 蛋白偶联受体 (GPCR) 的活性通过配体特性来描述，包括亲和力 (Ki)、效力 (IC50/EC50)、效能 (Emax) 和动力学 (Kon/Koff)。这些特性与配体的停留时间有关，这是体内药物-靶标相互作用的一般指标。最近的 GPCR 结构-功能突破都需要以某种方式稳定受体的配体，这突出了这些重要的细胞表面受体的自然不稳定性。这项研究开创了一个新的发现时代，强调了配体-受体相互作用的重要性，超越了传统思维。我们提出，受体稳定性与受体在细胞膜中的折叠和停留有关，这为研究受体功能提供了一个新的维度，应该加以考虑。
