Role of extracellular surface residues in agonist activation of the alpha1 adrenoceptor

大多数现代药物作用于一类被称为gpcr的细胞蛋白。尽管它们很重要，但对于从细胞外部起作用的激动剂如何产生GPCR结构的变化，从而使信号传导到细胞内部，人们知之甚少。我们已经在α 1肾上腺素能受体的细胞外表面发现了新的残基，这些残基显著影响激动剂的反应，为理解GPCR激活的分子过程和开发针对不同GPCR构象的药物打开了大门。

Most modern drugs act on a class of cellular proteins known as GPCRs. Despite their importance, little is known about how agonists acting from the outside of cells produce a change in GPCR structure allowing signalling to the cell's interior. We have identified new residues on the extracellular surface of the alpha1 adrenoceptor that dramatically affect agonist responses, opening the door to understanding the molecular process of GPCR activation and the development of drugs that can target different GPCR conformations.