The evolution and structure of aminergic G protein-coupled receptors.
An analysis of aligned sequences of the seven transmembrane segments of 59 aminergic G protein-coupled receptors (GPCRs) shows that their classification into subclasses based upon the nature of their ligands is over-simplified. Sequences similarity dendrograms indicate that the evolution of these receptors occurs at two sites (the G protein-coupling regions and the ligand binding site) and this results in convergent as well as divergent evolution. Amino acid substitution patterns at each position in the alignment discriminate between the internal residues and those that face the lipid and the periodicity in these patterns matches that of the classical alpha-helix. The point at which the fifth transmembrane helix protrudes into the cytoplasm and the point at which the seventh transmembrane helix protrudes on the extracellular side of the bilayer are detected. The positions of charged residues on the external face of the remaining helices are used to determine the point at which they enter and leave the bilayer. These data are used to construct three-dimensional models of GPCRs, which are based on the recently determined arrangement of the helices of bovine rhodopsin rather than on the structure of bacteriorhodopsin.
Donnelly
D
D
Department of Crystallography, Birkbeck College, London, U.K.
Findlay
J B
JB
Blundell
T L
TL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D005583:Fourier Analysis; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D018343:Receptors, Adrenergic, beta-2; D011956:Receptors, Cell Surface; D012243:Rhodopsin; D019204:GTP-Binding Proteins