Journal
TRENDS IN PHARMACOLOGICAL SCIENCES
Volume 40, Issue 4, Pages 236-239Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2019.02.005
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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.
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