An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors.
A model for the alpha-carbon positions in the seven transmembrane helices in the rhodopsin family of G-protein-coupled receptors is presented. The model incorporates structural information derived from the analysis of approximately 500 sequences in this family. The location, relative to the centre of the lipid bilayer, of each of the seven helical sequence segments and their probable lengths are deduced from sequence analysis, along with the orientation, relative to the centre of the helix bundle, of each helical segment around its axis. The packing of the helices in the model is guided by the density in a three-dimensional map of frog rhodopsin determined by electron cryo-microscopy. The model suggests which of the residues that are highly conserved in this family of receptors interact with each other. Helices III, V and VI are predicted to protrude more than the others from the central lipid core towards the aqueous phase on the intracellular side of the membrane. This feature could be a property of the receptor structure in some but not all of the conformations that it adopts, since recent studies suggest that relative movement occurs between these helices on photoactivation of rhodopsin. Results from other techniques, including the creation of metal-binding sites and disulphide bridges, site-directed spin-labelling studies, the substituted-cysteine accessibility method and other site-directed mutagenesis studies, are discussed in terms of the model.
Baldwin
J M
JM
MRC Laboratory of Molecular Biology, Medical Research Council Centre, Hills Road, Cambridge, CB2 2QH, U.K.
Schertler
G F
GF
Unger
V M
VM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002244:Carbon; D017124:Conserved Sequence; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008051:Lipid Bilayers; D008958:Models, Molecular; D011956:Receptors, Cell Surface / Q000737:chemistry*; D012160:Retina / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry*; D017421:Sequence Analysis; D013698:Templates, Genetic
D008024:Ligands; D008051:Lipid Bilayers; D011956:Receptors, Cell Surface; D002244:Carbon; D012243:Rhodopsin; D019204:GTP-Binding Proteins