GPCR Activation

Activation mechanism of GPCRs

G protein-coupled receptors (GPCRs) (also called 7TM receptors) form a large superfamily of membrane proteins, which can be activated by small molecules, lipids, hormones, peptides, light, pain, taste and smell etc. Although 27% of the drugs in market target GPCRs, only 4% are targeted therapeutically. Activation of GPCRs take place by “molecular switches” which include the ionic lock switch, 3-7 lock switch, tyrosine toggle switch linked with the NPxxY motif in TM7, and transmission switch (Fig 2) (1). The detailed knowledge of the GPCR activation mechanism could be very useful in designing specific drugs. We proposed novel activation mechanism of cannabinoid receptors (2), and elucidated the role of water in the activation of formyl peptide receptor (FPR1) (3)

Fig 1. Activation Switches in GPCRs


  1. Trzaskowski B, Latek D, Yuan S, Ghoshdastider U, Debinski A, et al. (2012) Action of molecular switches in GPCRs–theoretical and experimental studies. Curr Med Chem 19: 1090–1109.
  2. Latek D, Kolinski M, Ghoshdastider U, Debinski A, Bombolewski R, et al. (2011) Modeling of ligand binding to G protein coupled receptors: cannabinoid CB1, CB2 and adrenergic β 2 AR. J Mol Model 17: 2353–2366. doi:10.1007/s00894-011-0986-7.
  3. Yuan S, Ghoshdastider U, Trzaskowski B, Latek D, Debinski A, et al. (2012) The role of water in activation mechanism of human Nformyl Peptide Receptor 1 (FPR1) based on molecular dynamics simulations. PloS One.