title: Evolutionary conservation of both the hydrophilic and hydrophobic nature of transmembrane residues.
abstract: An algorithm (HRG), developed to allow the pairwise comparisons of the aligned residues of several members of large gene families of polytopic integral membrane proteins is described. Using hydrophobicity scales, application of this algorithm allows the number and size of the membrane-spanning domains of bacteriorhodopsin, a polytopic protein whose structure has been partially determined, to be predicted with a high degree of accuracy (sensitivity 94%, specificity 82% for predicting the membrane embedded or extramembranous location of residues). As opposed to previously reported structure-prediction algorithms, delineation of putative transmembrane segments from connecting loops is also more clearly evident with the application of the HRG algorithm, even with proteins from widely divergent species. This indicates strong evolutionary pressure for the conservation of both the hydrophobic and hydrophilic character of residues in membrane-embedded regions of polytopic proteins, such as those of the G-protein-coupled receptor superfamily. These and other structural and functional implications evident from the application of the HRG algorithm are considered.
authors.affiliation: Department of Cardiovascular Biology, Cleveland Clinic Foundation, OH 44195, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Riek
authors.forename: M D
authors.initials: MD
authors.lastname: Handschumacher
authors.forename: S S
authors.initials: SS
authors.lastname: Sung
authors.forename: M
authors.initials: M
authors.lastname: Tan
authors.forename: M J
authors.initials: MJ
authors.lastname: Glynias
authors.forename: M D
authors.initials: MD
authors.lastname: Schluchter
authors.forename: J
authors.initials: J
authors.lastname: Novotny
authors.forename: R M
authors.initials: RM
authors.lastname: Graham
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001436:Bacteriorhodopsins / Q000235:genetics; D017124:Conserved Sequence; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014867:Water / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D014867:Water; D001436:Bacteriorhodopsins