The conformational switch in 7-transmembrane receptors: the muscarinic receptor paradigm.
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.
Hulme
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Division of Physical Biochemistry, National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK. e-hulme@nimr.mrc.ac.uk
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Ward
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Allman
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Curtis
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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*
D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins