An analysis of the conserved residues between halobacterial retinal proteins and G-protein coupled receptors: implications for GPCR modeling.
An alignment of the transmembrane domains of halobacterial retinal proteins (including bacteriorhodopsin) and G-protein coupled receptors (GPCRs) is presented based on the commonality of conserved residues between families. Due to the limited sequence homology displayed by these proteins, an alternative strategy is proposed for sequence alignment that correlates residues within secondary structure elements. The nonsequential alignment developed identifies three proline and two aspartates residues that share common positions and, in the former case, similar functions in the transmembrane domain. The alignment is further applied to model the packing of transmembrane helices 5 and 6 of the beta-adrenergic receptor based on the backbone coordinates of bacteriorhodopsin helices 3 and 2, respectively. Unlike models derived from standard sequential alignments, the approach developed here allows the key structural features conferred by the proline residues to be captured during model building. The structure described is also compared with available site directed mutagenesis results as well as existing GPCR models. In addition to the implications to model building, the commonality observed suggests a potential relationship among the GPCRs and retinal proteins.
Metzger
T G
TG
Department of Medicinal Chemistry, University of Minnesota, Minneapolis 55455, USA.
Paterlini
M G
MG
Portoghese
P S
PS
Ferguson
D M
DM
D000595:Amino Acid Sequence; D001436:Bacteriorhodopsins / Q000737:chemistry* / Q000235:genetics*; D003198:Computer Simulation; D017124:Conserved Sequence; D019204:GTP-Binding Proteins / Q000737:chemistry*; D006217:Halobacterium / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D011956:Receptors, Cell Surface; D001436:Bacteriorhodopsins; D019204:GTP-Binding Proteins