Does Divergent Binding Pocket Closure Drive Ligand Bias for Class A GPCRs?

Publication date: Available online 6 March 2019Source: Trends in Pharmacological SciencesAuthor(s): Marcel Bermudez, Andreas BockGPCRs 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.
Source: Trends in Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research