Skip to main content
Log in

New insights into the allergenicity of tropomyosin: a bioinformatics approach

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The invertebrate panallergen tropomyosin is a protein with an extremely simple folding. This makes it a perfect target for investigating structural differences between invertebrate and vertebrate tropomyosins, which are not considered allergenic. Phylogenetic and sequence analyses were conducted in order to explore the differences in primary structure between several tropomyosins and to promote an experimental development in the field of food allergy, based on the study of tropomyosin. The phylogenetic analyses showed that tropomyosin is a useful evolutionary marker. The phylogenetic trees obtained with tropomyosin were not always phylogenetically correct, but they might be useful for allergen avoidance by tropomyosin allergic individuals. Sequence analyses revealed that the probability of alpha helix folding in invertebrate tropomyosins was lower than in all the studied vertebrate ones, except for the Atlantic bluefin tuna Thunnus thynnus tropomyosin. This suggested that the lack of alpha helix folding may be involved in the immunogenicity of tropomyosins. More specifically, the regions adjacent to the positions 133–135 and 201 of the invertebrate tropomyosins, presented lower probability of alpha helix folding than those of vertebrates and are candidates to be responsible for their allergenicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Taylor SL (2008) Molluscan shellfish allergy. Adv Food Nutr Res 54:139–177

    Article  CAS  PubMed  Google Scholar 

  2. Woo CK, Bahna SL (2011) Not all shellfish “allergy” is allergy! Clin Transl Allergy 1:3

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Rico Díaz MA (2007) Estudio de la alergia al marisco en el área de sanitaria de A Coruña. Dissertation, Universidad de La Coruña

  4. Daul CB, Slattery M, Reese G, Lehrer SB (1994) Identification of the major brown shrimp (Penaeus aztecus) allergen (Pen a 1) as the muscle protein tropomyosin. Int Arch Allergy Immunol 105:49–55

    Article  CAS  PubMed  Google Scholar 

  5. Shanti KN, Martin BM, Nagpal S, Metcalfe DD, Rao PV (1993) Identification of tropomyosin as the major shrimp allergen and characterization of its IgE-binding epitopes. J Immunol 151:5354–5363

    CAS  PubMed  Google Scholar 

  6. Kunimoto A, Sisino T, Sakai K, Matsumoto T, Takahashi K, Yamashita H, Hiemori M, Tsuji H, Kimoto M (2009) Molecular cloning and allergenicity of Pen j 1, a major allergen of kuruma prawn, Penaeus japonicus. Biosci Biotechnol Biochem 73:840–848

    Article  CAS  PubMed  Google Scholar 

  7. Jenkins JA, Breiteneder H, Mills EN (2007) Evolutionary distance from human homologs reflects allergenicity of animal food proteins. J Allergy Clin Immunol 120:1399–1405

    Article  CAS  PubMed  Google Scholar 

  8. Santiago HC, Bennuru S, Boyd A, Eberhard M, Nutman TB (2011) Structural and immunologic cross-reactivity among filarial and mite tropomyosin: implications for the higiene hypothesis. J Allergy Clin Immunol 127:479–486

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Liu R, Holck AL, Yang E, Liu C, Xue W (2013) Tropomyosin from tilapia (Oreochromis mossambicus) as an allergen. Clin Exp Allergy 43:365–377

    Article  CAS  PubMed  Google Scholar 

  10. Fitzsimmons CM, Dunne DW (2009) Survival of the fittest: allergology or parasitology? Trends Parasitol 25:447–451

    Article  PubMed  Google Scholar 

  11. Asturias JA, Eraso E, Moneo I, Martínez A (2000) Is tropomyosin an allergen in Anisakis? Allergy 55:898–899

    Article  CAS  PubMed  Google Scholar 

  12. Smillie LB (1979) Structure and functions of tropomyosins from muscle and non-muscle sources. Trends Biochem Sci 4:151–155

    Article  CAS  Google Scholar 

  13. Sigrist CJ, Cerutti L, Hulo N, Gattiker A, Falquet L, Pagni M, Bairoch A, Bucher P (2002) PROSITE: a documented database using patterns and profiles as motif descriptors. Brief Bioinform 3:265–274

    Article  CAS  PubMed  Google Scholar 

  14. Asturias JA, Eraso E, Martínez A (2000) Cloning and high level expression in Escherichia coli of an Anisakis simplex tropomyosin isoform. Mol Biochem Parasitol 108:263–267

    Article  CAS  PubMed  Google Scholar 

  15. Jeong KY, Hong CS, Yong TS (2006) Allergenic tropomyosins and their cross-reactivities. Protein Pept Lett 13:835–845

    Article  CAS  PubMed  Google Scholar 

  16. Shanti KN, Martin BM, Nagpal S, Metcalfe DD, Rao PV (1993) Identification of tropomyosin as the major shrimp allergen and characterization of its IgE-binding epitopes. J Immunol 151:5354–5363

    CAS  PubMed  Google Scholar 

  17. Reese G, Ayuso R, Carle T, Lehrer SB (1999) IgE-binding epitopes of shrimp tropomyosin, the major allergen Pen a 1. Int Arch Allergy Immunol 118:300–301

    Article  CAS  PubMed  Google Scholar 

  18. Reese G, Ayuso R, Lehrer SB (1999) Tropomyosin: an invertebrate pan-allergen. Int Arch Allergy Immunol 119:247–258

    Article  CAS  PubMed  Google Scholar 

  19. Ayuso R, Sanchez-García S, Pascal M, Lin J, Grishina G, Fu Z, Ibanez MD, Sastre J, Sampson HA (2012) Is epitope recognition of shrimp allergens useful to predict clinical reactivity? Clin Exp Allergy 42:293–304

    Article  CAS  PubMed  Google Scholar 

  20. Ayuso R, Sánchez-Garcia S, Lin J, Fu Z, Ibáñez MD, Carrillo T, Blanco C, Goldis M, Bardina L, Sastre J, Sampson HA (2010) Greater epitope recognition of shrimp allergens by children than by adults suggests that shrimp sensitization decreases with age. J Allergy Clin Immunol 125:1286–1293

    Article  CAS  PubMed  Google Scholar 

  21. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) ClustalW and ClustalX version 2.0. Bioinformatics 23:2947–2948

    Article  CAS  PubMed  Google Scholar 

  22. Nicholas KB, Nicholas HB (1997) GeneDoc: a tool for editing and annotating multiple sequence alignments. Distributed by the author, http://www.nrbsc.org/downloads/

  23. García-Boronat M, Diez-Rivero CM, Reinherz EL, Reche PA (2008) PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery. Nucleic Acids Res 36:35–41

    Article  Google Scholar 

  24. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: Molecular Evolutionary Genetics Analysis using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods. Mol Biol Evol 28:2731–2739

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O (2010) New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biology 59:307–321

    Article  CAS  Google Scholar 

  26. Garnier J, Gibrat JF, Robson B (1996) GOR secondary structure prediction method version IV. Meth Enzymol 266:540–553

    Article  CAS  PubMed  Google Scholar 

  27. Combet C, Blanchet C, Geourjon C, Deléage G (2000) NPS@: Network Protein Sequence Analysis. TIBS 25:147–150

    CAS  PubMed  Google Scholar 

  28. Felsenstein J (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791

    Article  Google Scholar 

  29. Zuckerkandl E, Pauling L (1965) Evolutionary divergence and convergence in proteins. In: Bryson V, Vogel HJ (eds) Evolving Genes and Proteins. Academic Press, New York, pp 97–166

    Google Scholar 

  30. Sneath PHA, Sokal RR (1973) Numerical Taxonomy. Freeman W H and Company, San Francisco

    Google Scholar 

  31. Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    CAS  PubMed  Google Scholar 

  32. Rzhetsky A, Nei M (1992) A simple method for estimating and testing minimum evolution trees. Mol Biol Evol 9:945–967

    CAS  Google Scholar 

  33. Nei M, Kumar S (2000) Molecular Evolution and Phylogenetics. Oxford University Press, New York

    Google Scholar 

  34. Le SQ, Gascuel O (2008) An improved general amino acid replacement matrix. Mol Biol Evol 25:1307–1320

    Article  CAS  PubMed  Google Scholar 

  35. Gascuel O (1997) BIONJ: an improved version of the NJ algorithm based on a simple model of sequence data. Mol Biol Evol 14:685–695

    Article  CAS  PubMed  Google Scholar 

  36. Abascal F, Zardoya R, Posada D (2005) ProtTest: selection of best-fit models of protein evolution. Bioinformatics 21:2104–2105

    Article  CAS  PubMed  Google Scholar 

  37. Wang X, Li L, Xu F, Zhang G (2011) Tropomyosin is a nice marker gene for phylogenetic analysis of molluscs. Mol Biol Rep 38:4589–4593

    Article  CAS  PubMed  Google Scholar 

  38. Peña C (2011) Métodos de inferencia filogenética. Rev Peru Biol 18:265–267

    Article  Google Scholar 

  39. FAO/WHO (2001) Evaluation of Allergenicity of Genetically Modified Foods. Report of a Joint FAO/WHO Expert Consultation on Allergenicity of Foods Derived from Biotechnology. FAO, Rome

  40. FAO/WHO (2009) Guideline for the conduct of food safety assessment of foods derived from recombinant DNA plants. In WHO/FAO (ed) Codex Alimentarius Guidelines. Foods derived from modern biotechnology, 2nd edn. FAO, Rome pp 52–55

  41. García BE, Lizaso MT (2011) Cross-reactivity syndromes in food allergy. J Investig Allergol Clin Immunol 21:162–170

    PubMed  Google Scholar 

  42. Van Do T, Elsayed S, Florvaag E, Hordvik I, Endresen C (2005) Allergy to fish parvalbumins: studies on the cross-reactivity of allergens from 9 commonly consumed fish. J Allergy Clin Immunol 116:1314–1320

    Article  PubMed  Google Scholar 

  43. Tsabouri S, Triga M, Makris M, Kalogeromitros D, Church MK, Priftis KN (2012) Fish and shellfish allergy in children: review of a persistent food allergy. Pediatr Allergy Immunol 23:608–615

    Article  PubMed  Google Scholar 

  44. Fernandes J, Reshef A, Patton L, Ayuso R, Reese G, Lehrer SB (2003) Immunoglobulin E antibody reactivity to the major shrimp allergen, tropomyosin, in unexposed Orthodox Jews. Clin Exp Allergy 33:956–961

    Article  CAS  PubMed  Google Scholar 

  45. Ghosh D, Gupta-Bhattacharya S (2008) Structural insight into protein T1, the non-allergenic member of the Bet v 1 allergen family-An in silico analysis. Mol Immunol 45:456–462

    Article  CAS  PubMed  Google Scholar 

  46. Blair JE (2009) Animals (Metazoa). In: Hedges SB, Kumar S (eds) The Timetree of Life. Oxford University Press, Oxford, pp 223–230

    Google Scholar 

  47. Fitch WM, Margoliash E (1967) Construction of phylogenetic trees. Science 155:279–284

    Article  CAS  PubMed  Google Scholar 

  48. González-de-Olano D, Bartolomé B, Maroto AS, Vivanco F, Pastor-Vargas C (2012) Asthma after chicken consumption due to cross-reactivity between fish and chicken parvalbumin. J Investig Allergol Clin Immunol 22:227–228

    PubMed  Google Scholar 

  49. Restani P, Ballabio C, Tripodi S, Fiocchi A (2009) Meat allergy. Curr Opin Allergy Clin Immunol 9:265–269

    Article  CAS  PubMed  Google Scholar 

  50. Greenfield NJ, Hitchcock-DeGregori SE (1995) The stability of tropomyosin, a two stranded coiled-coil protein, is primarily a function of the hydrophobicity of residues at the helix-helix interface. Biochemistry 34:16797–16805

    Article  CAS  PubMed  Google Scholar 

  51. Sumida JP, Wu E, Lehrer SS (2008) Conserved Asp-137 imparts flexibility to tropomyosin and affects function. J Biol Chem 283:6728–6734

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The present study was supported by the Ramón Areces Foundation. JGF is supported by a PhD fellowship from Universidad Complutense de Madrid. We thank José Castresana for useful comments and three anonymous reviewers that helped improve the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Juan González-Fernández.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

González-Fernández, J., Rodero, M., Daschner, A. et al. New insights into the allergenicity of tropomyosin: a bioinformatics approach. Mol Biol Rep 41, 6509–6517 (2014). https://doi.org/10.1007/s11033-014-3534-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3534-6

Keywords

Navigation