title: The conformational switch in 7-transmembrane receptors: the muscarinic receptor paradigm.
abstract: 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.
authors.affiliation: Division of Physical Biochemistry, National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK. e-hulme@nimr.mrc.ac.uk
authors.forename: E C
authors.initials: EC
authors.lastname: Hulme
authors.forename: Z L
authors.initials: ZL
authors.lastname: Lu
authors.forename: S D
authors.initials: SD
authors.lastname: Ward
authors.forename: K
authors.initials: K
authors.lastname: Allman
authors.forename: C A
authors.initials: CA
authors.lastname: Curtis
mesh_terms: D001665:Binding Sites; D002462:Cell Membrane / Q000648:ultrastructure*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008968:Molecular Conformation; D016297:Mutagenesis, Site-Directed / Q000235:genetics*; D011950:Receptors, Cholinergic / Q000737:chemistry*; D011976:Receptors, Muscarinic / Q000737:chemistry*
chemical_list: D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins