The conformational switch in 7-transmembrane receptors: the muscarinic receptor paradigm

Eur J Pharmacol. 1999 Jun 30;375(1-3):247-60. doi: 10.1016/s0014-2999(99)00297-6.


The rhodopsin-like superfamily of 7-transmembrane receptors is the largest class of signalling molecules in the mammalian genome. Recently, a combination of mutagenesis, biophysical and modelling studies have suggested a credible model for the alpha-carbon backbone in the transmembrane region of the 7-transmembrane receptors, and have started to reveal the structural basis of the conformational switch from the inactive to the active state. A key feature may be the replacement of a network of radial constraints, centred on transmembrane helix three, which stabilise the inactive ground state of the receptor by a new set of axial interactions which help to stabilise the activated state. Transmembrane helix three may act as a rotary switch in the activation mechanism.

Publication types

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

MeSH terms

  • Binding Sites
  • Cell Membrane / ultrastructure*
  • GTP-Binding Proteins / metabolism*
  • Molecular Conformation
  • Mutagenesis, Site-Directed / genetics*
  • Receptors, Cholinergic / chemistry*
  • Receptors, Muscarinic / chemistry*


  • Receptors, Cholinergic
  • Receptors, Muscarinic
  • GTP-Binding Proteins