Advertisement

Journal of Molecular Modeling

, Volume 13, Issue 3, pp 401–409 | Cite as

Ligand specificity of odorant receptors

  • Kamil Khafizov
  • Claudio Anselmi
  • Anna Menini
  • Paolo CarloniEmail author
Original Paper

Abstract

Odorant receptors belong to class A of the G protein-coupled receptors (GPCRs) and detect a large number of structurally diverse odorant molecules. A recent structural bioinformatic analysis suggests that structural features are conserved across class A of GPCRs in spite of their low sequence identity. Based on this work, we have aligned the sequences of 29 ORs for which ligand binding data are available. Recent site-directed mutagenesis experiments on one such receptor (MOR174-9) provide information that helped to identify nine amino-acid residues involved in ligand binding. Our modeling provides a rationale for amino acids in equivalent positions in most of the odorant receptors considered and helps to identify other amino acids that could be important for ligand binding. Our findings are consistent with most of the previous models and allow predictions for site-directed mutagenesis experiments, which could also validate our model.

Keywords

Olfactory receptors Sequence alignment Odorant binding G protein-coupled receptor Homology modeling 

Abbreviations

OR

odorant receptor

3D

three-dimensional

SI

sequence identity

GPCR

G protein-coupled receptor

TM

transmembrane

Notes

Acknowledgements

We would like to thank Kazushige Touhara and Sayako Katada (University of Tokyo, Japan) for supplying the sequence alignment of bovine rhodopsin and MOR174-9 and the 3D-model structure of the latter, Dr. Alejandro Giorgetti (Università di Roma “La Sapienza”, Italy) for useful discussions and Manuela Schipizza Lough (SISSA/ISAS) for reading the text. This work was supported by INFM-Democritos.

Supplementary material

894_2006_160_MOESM1_ESM.pdf (30 kb)
Supplement 1 An alignment of OR’s sequences against bovine rhodopsin sequence is available as supplementary material (PDF 30 kb).

References

  1. 1.
    Menini A, Lagostena L, Boccaccio A (2004) News Physiol Sci 19:101–104Google Scholar
  2. 2.
    Buck L, Axel R (1991) Cell 65:175–187CrossRefGoogle Scholar
  3. 3.
    Mombaerts P (2004) Nat Rev Neurosci 5:263–278CrossRefGoogle Scholar
  4. 4.
    Godfrey PA, Malnic B, Buck LB (2004) Proc Natl Acad Sci USA 101:2156–2161CrossRefGoogle Scholar
  5. 5.
    Malnic B, Hirono J, Sato T, Buck LB (1999) Cell 96:713–723CrossRefGoogle Scholar
  6. 6.
    Freitag J, Beck A, Ludwig G, von Buchholtz L, Breer H (1999) Gene 226:165–174CrossRefGoogle Scholar
  7. 7.
    Zhang X, Firestein S (2002) Nat Neurosci 5:124–133Google Scholar
  8. 8.
    Saito H, Kubota M, Roberts RW, Chi Q, Matsunami H (2004) Cell 119:679–691CrossRefGoogle Scholar
  9. 9.
    Araneda RC, Kini AD, Firestein S (2000) Nat Neurosci 3:1248–1255CrossRefGoogle Scholar
  10. 10.
    Bozza T, Feinstein P, Zheng C, Mombaerts P (2002) J Neurosci 22:3033–3043Google Scholar
  11. 11.
    Gaillard I, Rouquier S, Pin JP, Mollard P, Richard S, Barnabe C, Demaille J, Giorgi D (2002) Eur J Neurosci 15:409–418CrossRefGoogle Scholar
  12. 12.
    Kajiya K, Inaki K, Tanaka M, Haga T, Kataoka H, Touhara K (2001) J Neurosci 21:6018–6025Google Scholar
  13. 13.
    Katada S, Nakagawa T, Kataoka H, Touhara K (2003) Biochem Biophys Res Commun 305:964–969CrossRefGoogle Scholar
  14. 14.
    Katada S, Hirokawa T, Oka Y, Suwa M, Touhara K (2005) J Neurosci 25:1806–1815CrossRefGoogle Scholar
  15. 15.
    Krautwurst D, Yau KW, Reed RR (1998) Cell 95:917–926CrossRefGoogle Scholar
  16. 16.
    Levasseur G, Persuy MA, Grebert D, Remy JJ, Salesse R, Pajot-Augy E (2003) Eur J Biochem 270:2905–2912CrossRefGoogle Scholar
  17. 17.
    Oka Y, Omura M, Kataoka H, Touhara K (2004) EMBO J 23:120–126CrossRefGoogle Scholar
  18. 18.
    Touhara K, Sengoku S, Inaki K, Tsuboi A, Hirono J, Sato T, Sakano H, Haga T (1999) Proc Natl Acad Sci USA 96:4040–4045CrossRefGoogle Scholar
  19. 19.
    Zhao H, Ivic L, Otaki JM, Hashimoto M, Mikoshiba K, Firestein S (1998) Science 279:237–242CrossRefGoogle Scholar
  20. 20.
    Kolakowski LF Jr (1994) Receptors Channels 2:1–7Google Scholar
  21. 21.
    Floriano WB, Vaidehi N, Goddard WA III, Singer MS, Shepherd GM (2000) Proc Natl Acad Sci USA 97:10712–10716CrossRefGoogle Scholar
  22. 22.
    Pebay-Peyroula E, Rummel G, Rosenbusch JP, Landau EM (1997) Science 277:1676–1681CrossRefGoogle Scholar
  23. 23.
    Singer MS, Shepherd GM (1994) Neuroreport 5:1297–1300Google Scholar
  24. 24.
    Singer MS, Oliveira L, Vriend G, Shepherd GM (1995) Receptors Channels 3:89–95Google Scholar
  25. 25.
    Afshar M, Hubbard RE, Demaille J (1998) Biochimie 80:129–135CrossRefGoogle Scholar
  26. 26.
    Schertler GF, Villa C, Henderson R (1993) Nature 362:770–772CrossRefGoogle Scholar
  27. 27.
    Schertler GF (1998) Eye 12 (Pt 3b):504–510Google Scholar
  28. 28.
    Singer MS (2000) Chem Senses 25:155–165CrossRefGoogle Scholar
  29. 29.
    Vaidehi N, Floriano WB, Trabanino R, Hall SE, Freddolino P, Choi EJ, Zamanakos G, Goddard WA III (2002) Proc Natl Acad Sci USA 99:12622–12627CrossRefGoogle Scholar
  30. 30.
    Lai PC, Singer MS, Crasto CJ (2005) Chem Senses 30:781–792CrossRefGoogle Scholar
  31. 31.
    Floriano WB, Vaidehi N, Goddard WA III (2004) Chem Senses 29:269–290CrossRefGoogle Scholar
  32. 32.
    Hall SE, Floriano WB, Vaidehi N, Goddard WA III (2004) Chem Senses 29:595–616CrossRefGoogle Scholar
  33. 33.
    Hummel P, Vaidehi N, Floriano WB, Hall SE, Goddard WA III (2005) Protein Sci 14:703–710CrossRefGoogle Scholar
  34. 34.
    Trabanino RJ, Hall SE, Vaidehi N, Floriano WB, Kam VW, Goddard WA III (2004) Biophys J 86:1904–1921CrossRefGoogle Scholar
  35. 35.
    Man O, Gilad Y, Lancet D (2004) Protein Sci 13:240–254CrossRefGoogle Scholar
  36. 36.
    Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Science 289:739–745CrossRefGoogle Scholar
  37. 37.
    Khalid S, Bond PJ, Deol SS, Sansom MS (2006) Proteins 63:6CrossRefGoogle Scholar
  38. 38.
    Oakhill JS, Sutton BJ, Gorringe AR, Evans RW (2005) Protein Eng Des Sel 18:221–228CrossRefGoogle Scholar
  39. 39.
    Zhang Y, Sham YY, Rajamani R, Gao J, Portoghese PS (2005) Chembiochem 6:853–859CrossRefGoogle Scholar
  40. 40.
    Eilers M, Hornak V, Smith SO, Konopka JB (2005) Biochemistry 44:8959–8975CrossRefGoogle Scholar
  41. 41.
    Thompson JD, Higgins DG, Gibson TJ (1994) Nucleic Acids Res 22:4673–4680CrossRefGoogle Scholar
  42. 42.
    Sali A, Blundell TL (1993) J Mol Biol 234:779–815CrossRefGoogle Scholar
  43. 43.
    Okada T, Sugihara M, Bondar AN, Elstner M, Entel P, Buss V (2004) J Mol Biol 342:571–583CrossRefGoogle Scholar
  44. 44.
    Cornell WD, Cieplak P, Bayly CI, Gould IR, Caldwell JW, Kollman PA (1995) J Am Chem Soc 117:5179–5197CrossRefGoogle Scholar
  45. 45.
    Lin JC, Parrish W, Eilers M, Smith SO, Konopka JB (2003) Biochemistry 42:293–301CrossRefGoogle Scholar
  46. 46.
    Liu W, Eilers M, Patel AB, Smith SO (2004) J Mol Biol 337:713–729CrossRefGoogle Scholar
  47. 47.
    Humphrey W, Dalke A, Schulten K (1996) J Mol Graph 14:33–38CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Kamil Khafizov
    • 1
    • 2
    • 3
  • Claudio Anselmi
    • 1
    • 2
    • 3
  • Anna Menini
    • 1
    • 3
  • Paolo Carloni
    • 1
    • 2
    • 3
    Email author
  1. 1.International School for Advanced StudiesTriesteItaly
  2. 2.INFM-DEMOCRITOS Modelling Centre for Research in Atomistic SimulationTriesteItaly
  3. 3.Italian Institute of TechnologyTriesteItaly

Personalised recommendations