Changeux and Christopoulos have recently described in Cell  how common mechanisms link the allosteric sites of activation and response within the four major receptor families of ligand- and voltage-gated ion channels, G-protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases. As stated in the classical “Monod-Wyman-Changeux” model , the signal transduction mechanism operates through the selective stabilization of the particular state to which any ligand preferentially binds. Recent research shows that these states are affected by multiple factors including oligomerization, distinct conformational ensembles, intrinsically disordered regions, and allosteric modulatory sites. These processes can be perturbed by mutations that shift the equilibrium of receptor functional states and lead to disease . Conversely, marketed medicines now include a large number of allosteric modulators with the advantages of fine-tune physiological responses and offer higher on-target selectivity via more diverse binding sites . Such modulators can also display increased functional selectivity through biased agonism (i.e. the association with a distinct receptor conformation and signal routing). This review summarises the unifying mechanisms for the allosteric modulation of receptor classes and provides a clear demonstration of the associated pharmacological targeting opportunities.
 Changeux, J.-P. and A. Christopoulos (2016). Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation. Cell. 166(5): p. 1084-1102. [PMID: 27565340]
 Monod, J., J. Wyman, and J.P. Changeux (1965). On the nature of allosteric transitions: a plausible model. J. Mol. Biol. 12: p.88-118. [PMID: 14343300]
 Changeux, J.-P. (2013). 50 years of allosteric interactions: the twists and turns of the models. Nat. Rev. Mol. Cell Biol. 14(12): p.819-29. [PMID: 24150612]
 Gentry, P.R., P.M. Sexton, and A. Christopoulos (2015). Novel Allosteric Modulators of G Protein-coupled Receptors. Journal of Biological Chemistry. 290(32): p.19478-19488. [PMID: 26100627]
Comments by David E. Gloriam (Department of Drug Design and Pharmacology, University of Copenhagen).