AAPS PharmSci

, 3:25 | Cite as

Evolutionary relationships among G protein-coupled receptors using a clustered database approach

Article

Abstract

Guanine nucleotide-binding proteincoupled receptors (GPCRs) comprise large and diverse gene families in fungi, plants, and the animal kingdom. GPCRs appear to share a common structure with 7 transmembrane segments, but sequence similarity is minimal among the most distant GPCRs. To reevaluate the question of evolutionary relationships among the disparate GPCR families, this study takes advantage of the dramatically increased number of cloned GPCRs. Sequences were selected from the National Center for Biotechnology Information (NCBI) nonredundant peptide database using iterative BLAST (Basic Local Alignment Search Tool) searches to yield a database of ∼1700 GPCRs and unrelated membrane proteins as controls, divided into 34 distinet clusters. For each cluster, separate position-specific matrices were established to optimize sequence comparisons among GPCRs. This approach resulted in significant alignments between distant GPCR families, including receptors for the biogenic amine/peptide, VIP/secretin, cAMP, STE3/MAP3 fungal pheromones, latrophilin, developmental receptors frizzled and smoothened, as well as the more distant metabotrobic glutamate receptors, the STE2/MAM2 fungal pheromone receptors, and GPR1, a fungal glucose receptor. On the other hand, alignment scores between these recognized GPCR clades with p40 (putative GPCR) and pml (putative GPCR), as well as bacteriorhodopsins, failed to support a finding of homology. This study provides a refined view of GPCR ancestry and serves as a reference database with hyperlinks to other sources. Moreover, it may facilitate database annotation and the assignment of orphan receptors to GPCR families.

References

  1. 1.
    Riek RP, Handschumacher MD, Sung SS, et al. Evolutionary conservation of both the hydrophilic and hydrophobic nature of transmembrane residues. J Theor Biol. 1995;172(3):245–258.PubMedCrossRefGoogle Scholar
  2. 2.
    Kolakowski LF Jr. GPCRDb: a G-protein-coupled receptor database. Receptors Channels. 1994;2:1–7.PubMedGoogle Scholar
  3. 3.
    Horn F, Weare J, Beukers MW, et al. GPCRDB: an, information system for G protein coupled receptors. Nucleic Acids Res. 1998;26:275–279.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Bargmann CI. Oltactory receptors, vomeronasal receptors, and the organization of olfactory information. Cell. 1997;90(4):585–587.PubMedCrossRefGoogle Scholar
  5. 5.
    Slusarski DC, Corces VG, Moon RT. Interaction of Wnt and a frizzled homologue triggers G-protein-linked phosphatidylinositol signalling. Nature. 1997;390(6658):410–413.PubMedCrossRefGoogle Scholar
  6. 6.
    Barnes MR, Duckworth DM, Beeley LJ. Frizzled proteins constitute a novel family of G protein-coupled receptors, most closely related to the Secretin family. Trends Pharmacol Sci. 1998;19(10):399–400.PubMedCrossRefGoogle Scholar
  7. 7.
    Robertson HM. Two large families of chemoreceptor genes in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae reveal extensive gene duplication. diversification, movement, and intron loss. Genome Res. 1998;8(5):449–463.PubMedGoogle Scholar
  8. 8.
    Sugita S, Ichtchenko K, Khvotchev M, SYdhof TC. Alpha-latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors: G-protein coupling not required for triggering exocytosis. J Biol Chem. 1998;273(49):32715–32724.PubMedCrossRefGoogle Scholar
  9. 9.
    Bockaert J, Pin JP. Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J. 1998;18(7):1723–1729.CrossRefGoogle Scholar
  10. 10.
    Wang D, SadŽe W, Quillan JM. Calmodulin binding to G protein-coupling domain of opioid receptors. J Biol Chem. 1999;274:22081–22088.PubMedCrossRefGoogle Scholar
  11. 11.
    Rees DC, DeAntonio L, Eisenberg D. Hydrophobic organization of membrane proteins. Science. 1989;245(491):510–513.PubMedCrossRefGoogle Scholar
  12. 12.
    Persson B, Argos P. Prediction of transmembrane segments in proteins utilising multiple sequence alignments. J Mol Biol. 1994;237(2):182–192.PubMedCrossRefGoogle Scholar
  13. 13.
    Persson B, Argos P. Prediction of membrane protein topology utilizing multiple sequence alignments J Protein Chem. 1997;16(5):453–457.PubMedCrossRefGoogle Scholar
  14. 14.
    Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215(3):403–410.PubMedCrossRefGoogle Scholar
  15. 15.
    Madden TL, Tatusov RL, Zhang J. Applications of network BLAST server. Methods Enzymol. 1996;266:131–141.PubMedCrossRefGoogle Scholar
  16. 16.
    Altschul SF, Madden TL, SchŠffer AA, et al. Gapped BLAST and PSIBLAST a new generation of protein database search programs. Nucleic Acids Res. 1997;25(17):3389–3402.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Josefsson LG. Evidence for kinship between diverse G-protein coupled receptors. Gene. 1999;239(2):333–340.PubMedCrossRefGoogle Scholar
  18. 18.
    Graul RC, SadŻe W. Evolutionary relationships among proteins probed by an iterative neighborhood cluster analysis (INCA): alignment of bacteriorhodopsins with the yeast sequence YRO2. Pharm Res. 1997;14(11);1533–1541.PubMedCrossRefGoogle Scholar
  19. 19.
    Eddy SR. Multiple alignments and sequence searches. Trends Guide to Bioinformatics. Elsevier Science. Trends Supplement; 15–18.Google Scholar
  20. 20.
    SchŠffer AA, Wolf YI, Ponting CP, Koonin EV, Aravind L, Altschul SF. IMPALA: matching a protein sequence against a collection of PSI-BLAST-constructed position-specific score matrices. Bioinformatics. 1999;15(12):1000–1011.CrossRefGoogle Scholar
  21. 21.
    Durbin R, Eddy S, Krogh A, Mitchison G. Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids. Cambridge University Press; 1998.Google Scholar
  22. 22.
    Bateman A, Birney E, Durbin R, Eddy SR, Howe KL, Sonnhammer EL. The Pfam protein families database. Nucleic Acids Res. 2000;28(1):263–266.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Kobilka BK, Frielle T, Collins S, et al. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature. 1987;329(6134):75–79.PubMedCrossRefGoogle Scholar
  24. 24.
    Olde B, McCombie WR. Molecular cloning and functional expression of a serotonin receptor from Caenorhabditis elegans. J Mol Neurosci. 1997;8(1):53–62.PubMedCrossRefGoogle Scholar
  25. 25.
    Dunn RJ, Hackett NR, Huang KS, et al. Studies on the light-transducing pigment bacteriorhodopsin. Cold Spring, Harb Symp Quant Biol 1983;48(Pt2):853–862.CrossRefGoogle Scholar
  26. 26.
    Hart AC, KrŠmer H, Van Vactor DLJ, Paidhungat M, Zipursky SL. Induction of cell fate in the Drosophila retina: the bride of sevenless protein is predicted to contain a large extracellular domain and seven transmembrane segments. Genes Dev. 1990;4(11):1835–1847.PubMedCrossRefGoogle Scholar
  27. 27.
    Klein PS, Sun TJ, Saxe CL 3rd, Kimmel AR, Johnson RL, Devreotes PN. A chemoattractant receptor controls development in Dictyostelium discoideum. Science. 1988;241(4872):1467–1472.PubMedCrossRefGoogle Scholar
  28. 28.
    Lewis MJ, Pelham HR. A human homologne of the yeast HDEL receptor. Nature. 1990;348(6297):162–163.PubMedCrossRefGoogle Scholar
  29. 29.
    Vinson CR, Conover S, Adler PN. A Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domains. Nature. 1989;338(6212)263–264.PubMedCrossRefGoogle Scholar
  30. 30.
    Alcedo J, Ayzenzon M, Von Ohlen T, Noll M, Hooper JE. The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal. Cell. 1996;86(2):221–232.PubMedCrossRefGoogle Scholar
  31. 31.
    Clark JA, Mezey E, Lam AS, Bonner TI. Distribution of the GABAB receptor subunit gb2 in rat CNS. Brain Res. 2000;860(1–2):41–52.PubMedCrossRefGoogle Scholar
  32. 32.
    Yun CW, Tamaki H, Nakayama R, Yamamoto K, Kumagai H. Gprotein coupled receptor from yeast Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1997;240(2):287–292.PubMedCrossRefGoogle Scholar
  33. 33.
    Kraakman L, Lemaire K, Ma P, et al., A Saccharomyces cerevisiae G-protein coupled receptor, Gprl, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose. Mol Microbiol. 1999;32(5):1002–1012.PubMedCrossRefGoogle Scholar
  34. 34.
    White GR, Varley JM, Heighway J Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer. Oncogene. 1998;17(26):3513–3519.PubMedCrossRefGoogle Scholar
  35. 35.
    Abe T, Tanemoto M, Nishio T, Hebert SC (unpublished). Metabotropic glutamate-like sequence in C. elegans.Google Scholar
  36. 36.
    Desai MA, Burnett JP, Mayne NG, Schoepp DD. Cloning and expression of a human metabotropic glutamate receptor 1 alpha: enhanced coupling on co-transfection with a glutamate transporter. Mol Pharmacol. 1995;48(4):648–657.PubMedGoogle Scholar
  37. 37.
    Bassi MT, Schiaffino MV, Renieri A, et al. Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome. Nature Gen. 1995;10(1):13–19.CrossRefGoogle Scholar
  38. 38.
    Sengupta P, Chou JH, Bargmann CI. odr-10 encodes a seven transmembrane domain olfactory receptor required for responses to the odorant diacetyl. Cell. 1996;84(6):899–909.PubMedCrossRefGoogle Scholar
  39. 39.
    Buck L, Axel R A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell. 1991;65(1):175–187.PubMedCrossRefGoogle Scholar
  40. 40.
    Mayer H, Salzer U, Breuss J, Ziegler S, Marchler-Bauer A, Prohaska R. Isolation molecular characterization, and tissue-specific expression of a novel putative G protein-coupled receptor. Biochim Biophys Acta. 1998;1395(3):301–308.PubMedCrossRefGoogle Scholar
  41. 41.
    Murphy PM, Malech HL. Nucleotide sequence of a cDNA encoding a protein with primary structural similarity to G-protein coupled receptors. Nucleic Acids Res. 1990;18(7):1896.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Hooper JE, Scott MP. The Drosophila patched, gene encodes a putative membrane protein required for segmental patterning. Cell. 1989;59(4):751–765.PubMedCrossRefGoogle Scholar
  43. 43.
    Regan JW, Bailey TJ, Pepperl DJ, et al. Cloning of a novel human prostaglandin receptor with characteristics of the pharmacologically defined EP2 subtype. Mol Pharmacol. 1994;46(2):213–220.PubMedGoogle Scholar
  44. 44.
    Liang R, Fei YJ, Prasad PD, et al. Human intestinal H+/peptide cotransporter: cloning functional expression, and chromosomal localization. J Biol Chem. 1995;270(12):6456–6463.PubMedCrossRefGoogle Scholar
  45. 45.
    Sherrington R, Rogaev EI, Liang Y, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimeras disease. Nature. 1995;375(6534):754–760.PubMedCrossRefGoogle Scholar
  46. 46.
    Cheng Y, Lotan R Molecular cloning and characterization of a novel retmoic acid-inducible gene that encodes a putative G protein-coupled receptor. J Biol Chem. 1998;273(52):35008–35015.PubMedCrossRefGoogle Scholar
  47. 47.
    Troemel ER, Chou JH, Dwyer ND, Colbert HA, Bargmann CI. Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans Cell. 1995;83(2):207–218.PubMedCrossRefGoogle Scholar
  48. 48.
    Burkholder AC, Hartwell LH. The yeast alpha-factor receptor: structural properties deduced from the sequence of the STE2 gene. Nucleic Acids Res. 1985;13(23):8463–8475.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Kitamura K, Shimoda C. The Schizosaccharomyces pombe MAM2 gene encodes a putative pheromone receptor which has a significant homology with the Saccharomyces cerevisiae STE2 protein. EMBO J. 1991;10(12):3743–3751.PubMedCentralPubMedGoogle Scholar
  50. 50.
    Hagen DC, McCaffrey G, Sprague GF Jr. Evidence the yeast STE3 gene encodes a receptor for the peptide pheromone a factor gene sequence and implications for the structure of the presumed receptor. Proc Natl Acad Sci USA. 1986;83(5):1418–1422.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Tanaka K, Davey J, Imai Y, Yamamoto M. Schizosaccharomyces pombe map3+ encodes the putative M-factor receptor. Mol Cell Biol. 1993;13(1):80–88.PubMedCentralPubMedGoogle Scholar
  52. 52.
    Sreedharan SP, Patel DR, Huang JX, Goetzl EJ. Cloning and functional expression of a human neuroendocrine vasoactive intestinal peptide receptor. Biochem Biophys Res Commun. 1993;193(2):546–553.PubMedCrossRefGoogle Scholar
  53. 53.
    Dulac C, Axel R A novel family of genes encoding putative pheromone receptors in mammals. Cell. 1995;83(2):195–206.PubMedCrossRefGoogle Scholar
  54. 54.
    Feldmann H, Aigle M, Aljinovic G, et al. Complete DNA sequence of yeast chromosome II. EMBO J. 1994;13(24):5795–5809.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Aljinovic G, Pohl TM. Sequence and analysis of 24 kb on chromosome II of Saccharomyces cerevisiae Yeast. 1995;11(5):475–479.PubMedCrossRefGoogle Scholar
  56. 56.
    Bieszke JA, Braun EL, Bean LE, Kang S, Natvig DO, Borkovich KA. The nop-1 gene of Neurospora crassa encodes a seven transmembrane helix retinal-binding protein homologous to archaeal thodopsins. Proc Natl Acad Sci USA. 1999;96(14):8034–8039.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Tusn‡dy GE, Simon I. Principles governing amino acid composition of integral membrane proteins: application to topology prediction. J Mol Biol. 1998;283(2):489–506.CrossRefGoogle Scholar
  58. 58.
    Brenner SE, Chothia C, Hubbard TJP. Assessing sequence comparison methods with reliable structurally identified distant evolutionary relationship. Proc Natl Acad Sci USA. 1998;95:6073–6078.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Retief JD. Phylogenetic analysis using PHYLIP. Methods Mol Biol. 2000;132:243–258.PubMedGoogle Scholar
  60. 60.
    Felder CB. Gratil RC, Lee AY, Merkle H-P, SadŽe W. The venus flytrap of periplasmic binding proteins an ancient protein module present in multiple drug receptors PharmSci. 1999;1(2)http://www.pharmsci.org/journal/.Google Scholar
  61. 61.
    Engelke G, Gutowski-Eckel Z, Hammelmann M, Entian KD. Biosynthesis of the lantibiotic nisin genomic organization and membrane localization of the NisB protein. Appl Environ Microbiol. 1992;58(11):3730–3743.PubMedCentralPubMedGoogle Scholar
  62. 62.
    Park J, Karplus K, Barrett C, et al. Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods. J Mol Biol. 1998;284:1201–1210.PubMedCrossRefGoogle Scholar
  63. 63.
    Bauer H, Mayer H, Marchler-Bauer A, Salzer U, Prohaska R. Characterization of p40/GPR69A as a peripheral membrane protein related to the lantibiotic synthetase component C. Biochem Biophys Res Commun. 2000;275(1):69–74.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2001

Authors and Affiliations

  1. 1.Incyte GenomicsPalo Alto
  2. 2.Departments of Biopharmaceutical Sciences and Pharmaceutical ChemistryUniversity of California San FranciscoSan Francisco

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