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Does divergent binding pocket closure drive ligand bias for class A GPCRs?

Authors

  • M. Bermudez
  • A. Bock

Journal

  • Trends in Pharmacological Sciences

Citation

  • Trends Pharmacol Sci 40 (4): 236-239

Abstract

  • 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.


DOI

doi:10.1016/j.tips.2019.02.005