Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Trends Pharmacol Sci. 2019 Apr;40(4):236-239. doi: 10.1016/j.tips.2019.02.005. Epub 2019 Mar 6.
GPCRs couple to intracellular transducer proteins, which reciprocally closes the extracellular ligand binding pocket, a process called allosteric coupling. Biased agonists preferentially stimulate receptor coupling to specific signaling pathways. Here, we postulate that agonists with extended binding modes selectively interfere with binding pocket closure, which results in divergent allosteric coupling, eventually leading to ligand bias.
G 蛋白偶联受体（GPCRs）与细胞内转导蛋白偶联，这种相互作用会导致细胞外配体结合口袋关闭，这个过程被称为变构偶联。具有偏向激活特性的激动剂优先刺激受体与特定信号通路偶联。在此，我们假设具有扩展结合模式的激动剂会选择性地干扰结合口袋的关闭，从而导致变构偶联的不同，最终导致配体偏向。
