Structural insights into G-protein-coupled receptor allostery

Nature. 2018 Jul;559(7712):45-53. doi: 10.1038/s41586-018-0259-z. Epub 2018 Jul 4.


G-protein-coupled receptors (GPCRs) are key cell-surface proteins that transduce external environmental cues into biochemical signals across the membrane. GPCRs are intrinsically allosteric proteins; they interact via spatially distinct yet conformationally linked domains with both endogenous and exogenous proteins, nutrients, metabolites, hormones, small molecules and biological agents. Here we explore recent high-resolution structural studies, which are beginning to unravel the atomic details of allosteric transitions that govern GPCR biology, as well as highlighting how the wide diversity of druggable allosteric sites across these receptors present opportunities for developing new classes of therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation* / drug effects
  • Animals
  • Binding Sites / drug effects
  • Cytosol
  • Humans
  • Models, Molecular
  • Protein Conformation / drug effects
  • Protein Multimerization / drug effects
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / classification
  • Receptors, G-Protein-Coupled / metabolism*


  • Receptors, G-Protein-Coupled