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NMR spectroscopy reveals common structural features of the birch pollen allergen Bet v 1 and the cherry allergen Pru a 1

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Abstract

A high percentage of birch pollen allergic patients also experience food hypersensitivity which results from common epitopes on the corresponding allergens. In order to analyze whether this observed cross-reactivity can be attributed to common structural features, the major birch pollen allergen Bet v 1 and the cherry allergen Pru a 1 were investigated by multidimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy. For the 17 kDa Bet v 1 a three-dimensional structure was calculated on the basis of 1344 experimental restraints. The structure is well defined showing average root mean square deviations of 0.67 and 1.15 Å for the backbone heavy atoms and all heavy atoms of residues 1–154, respectively. The major structural features include a seven-stranded antiparallel β-sheet that wraps around a long C-terminal α-helix, thereby forming a large cavity in the interior of the protein. This structure served as template for the generation of an NMR-based model of Pru a 1 by homology modelling in conjunction with 277 experimentally derived distance restraints. Comparison to the structure of Bet v 1 proves both structures to be highly similar concerning the elements of secondary structure as well as the shape and charge distribution of the protein surface. This finding is consistent with the observed cross-reactivity between both proteins and allows the delineation of common cross-reactive B-cell epitopes.

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References

  1. Kaplan A.P. (ed.): Allergy. New York: Churchill Livingston 1985.

    Google Scholar 

  2. Breiteneder H., Pettenburger K., Bito A., Valenta R., Kraft D., Rumpold H., Scheiner O., Breitenbach M.: EMBO J.8, 1935–1938 (1989)

    Google Scholar 

  3. Breiteneder H., Ferreira F., Reikertshofer A., Duchene M., Valenta R., Hoffmann-Sommergruber K., Ebner C., Breitenbach M., Kraft D., Scheiner O.: J. Allergy Clin. Immunol.90, 909–917 (1992)

    Article  Google Scholar 

  4. Breiteneder H., Ferreira F., Hoffmann-Sommergruber K., Ebner C., Breitenbach M., Rumpold H., Kraft D., Scheiner O.: Eur. J. Biochem.212, 355–362 (1993)

    Article  Google Scholar 

  5. Larsen J.N., Störman P., Ipsen H.: Mol. Immunol.29, 703–711 (1992)

    Article  Google Scholar 

  6. Breiteneder H., Hoffmann-Sommergruber K., O’Riordian G., Susani M., Ahorn H., Ebner C., Kraft D., Scheiner O.: Eur. J. Biochem.233, 484–489 (1995)

    Article  Google Scholar 

  7. Ebner C., Birkner T., Valenta R., Rumpold H., Breitenbach M., Scheiner O., Kraft D.: J. Allergy Clin. Immunol.88, 588–594 (1991)

    Article  Google Scholar 

  8. Vieths S., Janek K., Aulepp H., Petersen A.: Allergy50, 421–430 (1995)

    Article  Google Scholar 

  9. Scheurer S., Metzner K., Haustein D., Vieths S.: Mol. Immunol.34, 619–629 (1997)

    Article  Google Scholar 

  10. Somissch I.E., Schmelzer E., Kawallek P., Hahlbrock K.: Gen. Genet.213, 93–98 (1988)

    Article  Google Scholar 

  11. Walter M.H., Liu J.W., Grand C., Lamb C.J., Hess D.: Gen. Genet.222, 353–360 (1990)

    Article  Google Scholar 

  12. Crowell D., John M.E., Rusell D., Amasino R.M.: Plant Mol. Biol.18, 459–466 (1992)

    Article  Google Scholar 

  13. Vanek-Krebitz M., Hoffmann-Sommergruber K., Laimer Da Camara Machado M., Susani M., Ebner C., Kraft D., Scheiner O., Breiteneder H.: Biochem. Biophys. Res. Commun.2, 538–551 (1995)

    Article  Google Scholar 

  14. Ebner C., Birkner T., Valenta R., Rumpold H., Breitenbach M., Scheiner O., Kraft D.: J. Allergy Clin. Immunol.88, 588–594 (1991)

    Article  Google Scholar 

  15. Gajhede M., Osmark P., Poulsen F.M., Ipsen H., Larsen J.N., Joost van Neerven R.J., Schou C., Lowenstein H., Spangfort M.D.: Nat. Struct. Biol.3, 1040–1045 (1996)

    Article  Google Scholar 

  16. Boehm M., Rösch P.: Biol. Chem.378, 687–695 (1997)

    Article  Google Scholar 

  17. Nerkamp J.: Diploma Thesis, University of Bayreuth, Bayreuth, Germany 1998.

    Google Scholar 

  18. Marion D., Ikura M., Tschudin R., Bax A.: J. Magn. Reson.85, 393–399 (1989)

    Google Scholar 

  19. Kay L.E., Keifer P., Saarinen T.: J. Am. Chem. Soc.114, 10663–10665 (1992)

    Article  Google Scholar 

  20. Schleucher J., Sattler M., Griesinger C.: Angew. Chem.105, 1518–1521 (1993)

    Article  Google Scholar 

  21. Grzesiek S., Bax A.: J. Magn. Reson.96, 432–440 (1992)

    Google Scholar 

  22. Wittekind M., Mueller L.: J. Magn. Reson.101, 201–205 (1993)

    Article  Google Scholar 

  23. Grzesiek S., Bax A.: J. Am. Chem. Soc.114, 6291–6293 (1992)

    Article  Google Scholar 

  24. Muhandiram D.R., Kay L.E.: J. Magn. Reson. Ser. B103, 203–216 (1994)

    Article  Google Scholar 

  25. Kay L.E., Xu G.Y., Yamazaki T.: J. Magn. Reson. Ser. A109, 129–133 (1994)

    Article  Google Scholar 

  26. Emsley L., Bodenhausen G.: Chem. Phys. Lett.165, 469–476 (1990)

    Article  ADS  Google Scholar 

  27. Sattler M., Schleucher J., Griesinger C.: Prog. NMR Spectrosc.34, 93–158 (1999)

    Article  Google Scholar 

  28. Ikura M., Kay L.E., Bax A.: J. Biomol. NMR1, 299–304 (1991)

    Article  Google Scholar 

  29. Kay L.E., Xu G.Y., Singer A., Muhandiram D.R., Forman-Kay J.D.: J. Magn. Reson. Ser. B101, 333–337 (1993)

    Article  Google Scholar 

  30. Wijmenga S.S., Steensma E., van Mierlo C.P.M.: J. Magn. Reson.124, 459–467 (1997)

    Article  ADS  Google Scholar 

  31. Shaka A., Lee C.J., Pines A.: J. Magn. Reson.77, 274–293 (1988)

    Google Scholar 

  32. Vuister G.W., Bax A.: J. Am. Chem. Soc.115, 7772–7777 (1993)

    Article  Google Scholar 

  33. Talluri S., Wagner G.: J. Magn. Reson. Ser. B112, 200–205 (1996)

    Article  Google Scholar 

  34. Cavanagh J., Rance M.: J. Magn. Reson.96, 670–678 (1992)

    Google Scholar 

  35. Shaka A., Barker P.B., Freeman R.: J. Magn. Reson.64, 547–552 (1985)

    Google Scholar 

  36. Barkhuijsen H., de Beer R., Bovee W.M.M.J., van Ormondt D.: J. Magn. Reson.61, 465–481 (1985)

    Google Scholar 

  37. Press W.H., Teukolsky S.A., Vetterling W.T., Flannery B.P.: Numerical Recipes in C., 2nd edn. Cambridge: Cambridge University Press 1992.

    Google Scholar 

  38. Zhu G., Bax A.: J. Magn. Reson.90, 405–410 (1990)

    Google Scholar 

  39. Friedrich M.S.: J. Biomol. NMR5, 147–153 (1995)

    MathSciNet  Google Scholar 

  40. Live D.H., Davis D.G., Agosta W.C., Cowburn D.: J. Am. Chem. Soc.106, 1939–1941 (1984)

    Article  Google Scholar 

  41. Clore G.M., Gronenborn A.M., Nilges M., Ryan C.A.: Biochemistry26, 8012–8023 (1987)

    Article  Google Scholar 

  42. Kraulis P.J., Clore G.M., Nilges M., Jones T.A., Petterson G., Knowles J., Gronenborn A.M.: Biochemistry28, 7241–7257 (1989)

    Article  Google Scholar 

  43. Brünger A.T.: X-PLOR Version 3.1. Howard Hughes Institute and Yale University, New Haven, CT 1993.

    Google Scholar 

  44. Kharrat A., Macias M., Gibson T.J., Nilges M., Pastore A.: EMBO J.14, 3572–3584 (1995)

    Google Scholar 

  45. Berendsen H.J.C., Postma J.P.M., van Gunsteren W.F., DiNiola A., Haak J.R.: J. Chem. Phys.81, 3684–3690 (1984)

    Article  ADS  Google Scholar 

  46. Nilges M.: Proteins17, 297–309 (1993)

    Article  Google Scholar 

  47. Kabsch W., Sander C.: Biopolymers22, 2577–2637 (1983)

    Article  Google Scholar 

  48. Laskowski R.A., MacArthur M.W., Moss D.S., Thornton J.M.: J. Appl. Crystallogr.26, 283–291 (1993)

    Article  Google Scholar 

  49. Hutchinson E.G., Thornton J.M.: Protein Sci.5, 212–220 (1996)

    Article  Google Scholar 

  50. Kraulis P.J.: J. Appl. Crystallogr.24, 946–950 (1991)

    Article  Google Scholar 

  51. Merrit E.A., Murphy M.E.P.: Acta Crystallogr. D50, 869–873 (1994)

    Article  Google Scholar 

  52. Peitsch M.C.: Bio. Technology13, 658–660 (1995)

    Google Scholar 

  53. Peitsch M.C.: Biochem. Soc. Trans.24, 274–279 (1996)

    Google Scholar 

  54. Bacon D.J., Anderson W.F.: J. Mol. Graphics6, 219–220 (1988)

    Article  Google Scholar 

  55. Düx P., Rubinstenn Y., Vuister G.W., Mulder F.A., Hard K., Hoff W.D., Kroon W.D., Crielaard W., Hellingwerf K.J., Kaptein R.: Biochemistry37, 12689–12699 (1998)

    Article  Google Scholar 

  56. Pickford A.R., Potts J.R., Bright J.R., Phan I., Campbell I.D.: Structure5, 359–370 (1997)

    Article  Google Scholar 

  57. Sticht H., Pickford A.R., Potts J.R., Campbell I.D.: J. Mol. Biol.276, 177–187 (1998)

    Article  Google Scholar 

  58. Benjamin D.C., Berzofsky J.A., East I.J., Gurd F.R., Hannum C., Leach S.J., Margoliash E., Michael J.G., Miller A., Prager E.M., Reinlin M., Sercarz E.E., Smith-Gill S.J., Todd D.E., Wilson A.C.: Annu. Rev. Immunol.2, 67–101 (1984)

    Article  Google Scholar 

  59. Gajhede M., Osmark P., Poulsen F.M., Ipsen H., Larsen J.N., Joost van Neerven R.J., Schou C., Lowenstein H., Spangfort M.D.: Nat. Struct. Biol.3, 1040–1045 (1996)

    Article  Google Scholar 

  60. Spangfort M.D., Gajhede M., Osmark P., Poulsen F.M., Ipsen H., Larsen J.N., van Neerven R.J., Schou C., Lowenstein H.: Int. Arch. Allergy. Immunol.113, 243–245 (1997)

    Article  Google Scholar 

  61. Scheurer S., Son D.Y., Böehm M., Karamloo F., Franke S., Hoffmann A., Haustein D., Vieths S.: Mol. Immunol. (in press)

  62. Ferreira F., Ebner C., Kramer B., Casari G., Briza P., Kungl A.J., Grimm R., Jahn-Schmid B., Breiteneder H., Kraft D., Breitenbach M., Rheinberger H.J., Scheiner O.: FASEB J.12, 231–242 (1998)

    Google Scholar 

  63. Nicholls A.: GRASP: Graphical Representation and Analysis of Surface Properties. New York: Columbia University 1993.

    Google Scholar 

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Schweimer, K., Sticht, H., Nerkamp, J. et al. NMR spectroscopy reveals common structural features of the birch pollen allergen Bet v 1 and the cherry allergen Pru a 1. Appl. Magn. Reson. 17, 449–464 (1999). https://doi.org/10.1007/BF03162177

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  • DOI: https://doi.org/10.1007/BF03162177

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