Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Trends Pharmacol Sci. 2020 Jun;41(6):387-389. doi: 10.1016/j.tips.2020.04.003. Epub 2020 Apr 30.
The ability to design 'biased' drugs that selectively activate G protein-coupled receptor (GPCR) signaling pathways beneficial in treating a disease, while limiting their side effects, is of broad significance. Lee et al. move us a step closer to this important goal by identifying structural differences in the β-adrenoceptor in complex with β-arrestin 1 versus a G protein-mimicking nanobody.
设计“有偏见”的药物的能力,这些药物可以选择性地激活 G 蛋白偶联受体 (GPCR) 信号通路,有益于治疗疾病,同时限制其副作用,具有广泛的意义。Lee 等人通过识别与β-arrestin 1 复合的β-肾上腺素受体与模拟 G 蛋白的纳米抗体复合物之间的结构差异,朝着这一重要目标又迈进了一步。