Allosteric Modulation as a Unifying Mechanism for Receptor Function and Regulation

Cell. 2016 Aug 25;166(5):1084-1102. doi: 10.1016/j.cell.2016.08.015.


Four major receptor families enable cells to respond to chemical and physical signals from their proximal environment. The ligand- and voltage-gated ion channels, G-protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases are all allosteric proteins that carry multiple, spatially distinct, yet conformationally linked ligand-binding sites. Recent studies point to common mechanisms governing the allosteric transitions of these receptors, including the impact of oligomerization, pre-existing and functionally distinct conformational ensembles, intrinsically disordered regions, and the occurrence of allosteric modulatory sites. Importantly, synthetic allosteric modulators are being discovered for these receptors, providing an enriched, yet challenging, landscape for novel therapeutics.

Publication types

  • Review

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Animals
  • Disease / genetics
  • Drug Design
  • Humans
  • Ligand-Gated Ion Channels / agonists
  • Ligand-Gated Ion Channels / chemistry*
  • Ligands
  • Models, Chemical
  • Mutation
  • Protein Conformation
  • Protein Multimerization
  • Receptor Protein-Tyrosine Kinases / agonists
  • Receptor Protein-Tyrosine Kinases / chemistry*
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / chemistry*
  • Signal Transduction


  • Ligand-Gated Ion Channels
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • Receptor Protein-Tyrosine Kinases