Molecular switches in GPCRs

Curr Opin Struct Biol. 2019 Apr;55:114-120. doi: 10.1016/j.sbi.2019.03.017. Epub 2019 May 10.

Abstract

Molecular switches in GPCRs enable passing the signal from the agonist binding site, usually located close to the extracellular surface, to the intracellular part of the receptor. The switches are usually associated with conserved structural motifs on transmembrane helices (TMs), and they are accompanied by adjacent residues which provide the signal to the central residue in the toggle switch. In case of locks being the molecular switches, they are breaking (permanently or temporarily) upon agonist binding. Cascade action of switches is correlated with influx of water molecules to form a pathway linking both sides of the receptor. The switches remove the hydrophobic barriers and facilitate water movement while water molecules help to rearrange the hydrogen bond network inside the receptor.

Publication types

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

MeSH terms

  • Binding Sites
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Protein Domains
  • Protein Structure, Secondary
  • Receptors, G-Protein-Coupled / chemistry*
  • Water / chemistry

Substances

  • Receptors, G-Protein-Coupled
  • Water