title: Proposed arrangement of the seven transmembrane helices in the secretin receptor family.
abstract: An arrangement of the seven transmembrane alpha-helices of the G protein-coupled Secretin receptor family is proposed. The helices of 27 homologous receptor sequences were plotted as helical wheels. The solvent inaccessible portion of each helix was used to assign relative orientations. They were arranged according to two criteria: 1) conserved, hydrophilic residues and aligned positions with restricted volume changes face the other helices and 2) aligned positions with low identity and large volume change face the lipid. The positive inside rule confirms 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 using 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 modelling approach showed that six helices were within a 15 degrees derivation in the orientation and five helices were within a horizontal derivation of two residues. The largest orientational derivations of a helix were 40 degrees and the largest horizontal displacement was four residues. A long stretch of side chains predicted to possess low resistance to movement in helix V of the Secretin receptor family suggests an involvement in receptor activation. Comparison of the Secretin receptor family and the larger G protein-coupled Rhodopsin family showed many similarities, despite the lack of obvious sequence identity.
authors.affiliation: Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Denmark.
authors.forename: J W
authors.initials: JW
authors.lastname: Tams
authors.forename: S M
authors.initials: SM
authors.lastname: Knudsen
authors.forename: J
authors.initials: J
authors.lastname: Fahrenkrug
mesh_terms: D001436:Bacteriorhodopsins / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000737:chemistry* / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry / Q000378:metabolism
chemical_list: D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D001436:Bacteriorhodopsins; D012243:Rhodopsin