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Where have all the active receptor states gone?

Defining G protein–coupled receptor ligand efficacy and biased agonism in precise chemical terms is one challenge posed by the current structural data that exists for this receptor family. Concepts classically used for understanding enzymes and other nonreceptor proteins may lead us in the right direction.

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Figure 1: Agonist-induced changes observed in the backbone structure of GPCRs.
Figure 2: Cooperativity in 'one protein, two ligands' system.
Figure 3: Schematic representation of different modes of ligand bias.

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Correspondence to H Ongun Onaran or Tommaso Costa.

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Onaran, H., Costa, T. Where have all the active receptor states gone?. Nat Chem Biol 8, 674–677 (2012). https://doi.org/10.1038/nchembio.1024

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