The probable arrangement of the helices in G protein-coupled receptors.
G protein-coupled receptors form a large family of integral membrane proteins whose amino acid sequences have seven hydrophobic segments containing distinctive sequence patterns. Rhodopsin, a member of the family, is known to have transmembrane alpha-helices. The probable arrangement of the seven helices, in all receptors, was deduced from structural information extracted from a detailed analysis of the sequences. Constraints established include: (1) each helix must be positioned next to its neighbours in the sequence; (2) helices I, IV and V must be most exposed to the lipid surrounding the receptor and helix III least exposed. (1) is established from the lengths of the shortest loops. (2) is determined by considering: (i) sites of the most conserved residues; (ii) other sites where variability is restricted; (iii) sites that accommodate polar residues; (iv) sites of differences in sequence between pairs or within groups of closely related receptors. Most sites in the last category should be in unimportant positions and are most useful in determining the position and extent of lipid-facing surface in each helix. The structural constraints for the receptors are used to allocate particular helices to the peaks in the recently published projection map of rhodopsin and to propose a tentative three-dimensional arrangement of the helices in G protein-coupled receptors.
MRC Laboratory of Molecular Biology, Cambridge, UK.
J M
JM
Baldwin
D000595:Amino Acid Sequence; D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000648:ultrastructure*; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D011956:Receptors, Cell Surface / Q000648:ultrastructure*; D012243:Rhodopsin / Q000648:ultrastructure*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D012243:Rhodopsin; D019204:GTP-Binding Proteins