title: The structural evolution of a P2Y-like G-protein-coupled receptor.
abstract: Based on the now available crystallographic data of the G-protein-coupled receptor (GPCR) prototype rhodopsin, many studies have been undertaken to build or verify models of other GPCRs. Here, we mined evolution as an additional source of structural information that may guide GPCR model generation as well as mutagenesis studies. The sequence information of 61 cloned orthologs of a P2Y-like receptor (GPR34) enabled us to identify motifs and residues that are important for maintaining the receptor function. The sequence data were compared with available sequences of 77 rhodopsin orthologs. Under a negative selection mode, only 17% of amino acid residues were preserved during 450 million years of GPR34 evolution. On the contrary, in rhodopsin evolution approximately 43% residues were absolutely conserved between fish and mammals. Despite major differences in their structural conservation, a comparison of structural data suggests that the global arrangement of the transmembrane core of GPR34 orthologs is similar to rhodopsin. The evolutionary approach was further applied to functionally analyze the relevance of common scaffold residues and motifs found in most of the rhodopsin-like GPCRs. Our analysis indicates that, in contrast to other GPCRs, maintaining the unique function of rhodopsin requires a more stringent network of relevant intramolecular constrains.
authors.affiliation: Institute of Pharmacology, Medical Faculty, Free University Berlin, 14195 Berlin, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Schulz
authors.forename: Torsten
authors.initials: T
authors.lastname: Schöneberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers; D019143:Evolution, Molecular; D005399:Fishes; D006801:Humans; D007438:Introns; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017433:Protein Structure, Secondary; D049312:Receptors, Lysophospholipid; D018048:Receptors, Purinergic P2 / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013995:Time; D014714:Vertebrates / Q000145:classification / Q000235:genetics
chemical_list: D017931:DNA Primers; C118065:G-protein-coupled receptor 34; D049312:Receptors, Lysophospholipid; D018048:Receptors, Purinergic P2