PROPOSED ARRANGEMENT OF THE 7 TRANSMEMBRANE HELICES IN THE SECRETIN RECEPTOR FAMILY

An arrangement of the seven transmembrane alpha-helices of the G prote in-coupled Secretin receptor family is proposed. The helices of 27 hom ologous receptor sequences were plotted as helical wheels. The solvent inaccessible portion of each helix was used to assign relative orient ations. They were arranged according to two criteria: 1) conserved, hy drophilic residues and aligned positions with restricted volume change s face the other helices and 2) aligned positions with low identity an d large volume change face the lipid. The positive inside rule confirm s the assumption that loops connecting transmembrane helices I-II, III -IV, V-VI and the C-terminal part of the receptors are intracellular. Our model approach was tested using the Bacteriorhodopsin family. The use of volume changes at each position in the transmembrane helix was crucial for the good correlation of the orientation of the helices usi ng the model approach and the structure of bacteriorhodopsin solved by electron microscopy [Grigorieff N, Ceska TA, Downing KH, Baldwin JM, and Henderson R (1996) J Mol Biol 259 393-421]. The tests of our model ling approach showed that six helices were within a 15 degrees derivat ion in the orientation and five helices were within a horizontal deriv ation of two residues. The largest orientational derivations of a heli x were 40 degrees and the largest horizontal displacement was four res idues. A long stretch of side chains predicted to possess low resistan ce to movement in helix V of the Secretin receptor family suggests an involvement in receptor activation, Comparison of the Secretin recepto r family and the larger G protein-coupled Rhodopsin family showed many similarities, despite the lack of obvious sequence identity.