Three-dimensional structure of scorpion toxins: Towards a new model of interaction with potassium channels

Abstract

Scorpion venom contains various toxins which block ion-channels, responsible for either sodium, potassium, calcium or chloride membrane permeation. This review focuses on the three-dimensional structure of scorpion toxins specific for potassium channels, and on their structure–activity relationships. The overall fold of all these toxins is similar, despite their various specificities towards different types of potassium channels. Fine studies of the influence of punctual mutations of both toxins and channels have converged on a precise description of the scorpion toxins functional maps. From this knowledge, it now becomes possible to predict the specificity of a newly described scorpion toxin. The way is thus now open that leads to the design of new potent synthetic potassium channel blockers which in turn could be used as therapeutic drugs.

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References

  1. 1.

    Carbone, E., Wanke, E., Prestipino, G., Possani, L.D. and Maelicke, A., Nature, 296 (1982) 90.

    Google Scholar 

  2. 2.

    Miller, C., Moczydlowski, E., Latorre, R. and Philips, M., Nature, 313 (1985) 316.

    Google Scholar 

  3. 3.

    Kharrat, R., Mansuelle, P., Sampieri, F., Crest, M., Martin-Eauclaire, M.F., Rochat, H. and El Ayeb, M., FEBS Lett., 406 (1997) 284.

    Google Scholar 

  4. 4.

    Olamendi-Portugal, T., Gomez-Lagunas, F., Gurrola, G.B. and Possani, L.D., Biochem. J., 315 (1996) 977.

    Google Scholar 

  5. 5.

    Rogowski, R.S., Collins, J.H., O'Neill, T., Gustafson, T.A., Werkman, T.R., Rogowski, M.A., Tenenholz, T.C., Weber, D.J. and Blaustein, M.P., Mol. Pharmacol., 50 (1996) 1167.

    Google Scholar 

  6. 6.

    Lebrun, B., Romi-Lebrun, R., Martin-Eauclaire, M.F., Yasuda, A., Ishiguro, M., Oyama, Y., Pongs, O. and Nakajima, T., Biochem. J., 328 (1997) 321.

    Google Scholar 

  7. 7.

    Cornet, B., Bonmatin, J.M., Hetru, C., Hoffmann, J.A., Ptak, M. and Vovelle, F., Structure, 3 (1995) 435.

    Google Scholar 

  8. 8.

    Blanc, E., Lecomte, C., Van Rietschoten, J., Sabatier, J.M. and Darbon, H., Proteins, 29 (1997) 359.

    Google Scholar 

  9. 9.

    Krezel, A.M., Kasibhatla, C., Hidalgo, P., MacKinnon, R. and Wagner, G., Protein Sci., 4 (1995) 1478.

    Google Scholar 

  10. 10.

    Jaravine, V.A., Nolde, D.E., Reibarkh, M.J., Korolkova, Y.V., Kozlov, S.A., Pluzhnikov, K.A., Grishin, E.V. and Arseniev, A.S., Biochemistry, 36 (1997) 1223.

    Google Scholar 

  11. 11.

    Tenenholz, T.C., Rogowski, R.S., Collins, J.H., Blaustein, M.P. and Weber, D.J., Biochemistry, 36 (1997) 2763.

    Google Scholar 

  12. 12.

    Bontems, F., Roumestand, C., Gilquin, B., Menez, A. and Toma, F., Science, 254 (1991) 1521.

    Google Scholar 

  13. 13.

    Bontems, F., Gilquin, B., Roumestand, C., Menez, A. and Toma, F., Biochemistry, 31 (1992) 7756.

    Google Scholar 

  14. 14.

    Johnson, B.A. and Sugg, E.E., Biochemistry, 31 (1992) 8151.

    Google Scholar 

  15. 15.

    Aiyar, J., Withka, J.M., Rizzi, J.P., Singleton, D.H., Andrews, G.C., Lin, W., Boyd, J., Hanson, D.G., Simon, M., Dethlefs, B., Lee, C.L., Hall, J.E., Gutman, G.A. and Chandy, K.G., Neuron, 15 (1995) 1169.

    Google Scholar 

  16. 16.

    Martins, J.C., Zhang, W., Tartar, A., Lazdunski, M. and Borremans, F., FEBS Lett., 260 (1990) 249.

    Google Scholar 

  17. 17.

    Martins, J.C., Van de Ven, F.J.M. and Borremans, F.A.M., J. Mol. Biol., 253 (1995) 590.

    Google Scholar 

  18. 18.

    Meunier, S., Bernassau, J.M., Martin-Eauclaire, M.F., Van Rietschoten, J., Cambillau, C. and Darbon, H., Biochemistry, 32 (1993) 11969.

    Google Scholar 

  19. 19.

    Johnson, B.A., Stevens, S.P. and Williamson, J.M., Biochemistry, 33 (1994) 15061.

    Google Scholar 

  20. 20.

    Delepierre, M., Prochkina-Chalufour, A. and Possani, L.D., Biochemistry, 36 (1997) 2649.

    Google Scholar 

  21. 21.

    Dauplais, M., Gilquin, B., Possani, L.D., Gurrola-Briones, G., Roumestand, C. and Menez, A., Biochemistry, 34 (1995) 16563.

    Google Scholar 

  22. 22.

    Blanc, E., Sabatier, J.M., Kharrat, R., Meunier, S., El Ayeb, M., Van Rietschoten, J. and Darbon, H., Proteins, 29 (1997) 321.

    Google Scholar 

  23. 23.

    Blanc, E., Frémont, V., Sizun, P., Meunier, S., Van Rietschoten, J., Thevand, A., Bernassau, J.M. and Darbon, H., Proteins, 24 (1996) 359.

    Google Scholar 

  24. 24.

    Sandberg, B.E., Int. J. Pept. Protein Res., 13 (1979) 327.

    Google Scholar 

  25. 25.

    Labbé-Jullié, C., Granier, C., Albericio, F., Defendini, M.L., Ceard, B., Rochat, H. and Van Rietschoten, J., Eur. J. Biochem., 196 (1991) 639.

    Google Scholar 

  26. 26.

    Devaux, C., Knibiehler, M., Defendini, M.L., Mabrouk, K., Rochat, H., Van Rietschoten, J., Baty, D. and Granier, C., Eur. J. Biochem., 231 (1995) 544.

    Google Scholar 

  27. 27.

    Chicchi, G.G., Gimenez-Gallego, G., Ber, E., Garcia, M.L., Winquist, R. and Cascieri, M., J. Biol. Chem., 263 (1988) 10192.

    Google Scholar 

  28. 28.

    Auguste, P., Hugues, M., Gravé, B., Gesquière, J.C., Maes, P., Tartar, A., Romey, G., Schweitz, H. and Lazdunski, M., J. Biol. Chem., 265 (1990) 4753.

    Google Scholar 

  29. 29.

    Sabatier, J.M., Zerrouck, H., Darbon, H., Mabrouk, K., Benslimane, A., Rochat, H., Martin-Eauclaire, M.F. and Van Rietschoten, J., Biochemistry, 32 (1993) 2763.

    Google Scholar 

  30. 30.

    Sabatier, J.M., Frémont, V., Mabrouk, K., Crest, M., Darbon, H., Rochat, H., Van Rietschoten, J. and Martin-Eauclaire, M.F., Int. J. Pept. Protein Res., 43 (1994) 486.

    Google Scholar 

  31. 31.

    Inisan, A.G., Meunier, S., Fedelli, O., Altbach, M., Frémont, V., Sabatier, J.M., Thevan, A., Bernassau, J.M., Cambillau, C. and Darbon, H., Int. J. Pept. Protein Res., 45 (1995) 441.

    Google Scholar 

  32. 32.

    Anderson, C.S., McKinnon, R., Smith, C. and Miller, C., J. Gen. Phys., 91 (1988) 317.

    Google Scholar 

  33. 33.

    McKinnon, R. and Miller, C., J. Gen. Phys., 91 (1988) 335.

    Google Scholar 

  34. 34.

    Park, C.S. and Miller, C., Biochemistry, 31 (1992) 7749.

    Google Scholar 

  35. 35.

    Goldstein, S.A.N. and Miller, C., Biophys. J., 65 (1993) 1613.

    Google Scholar 

  36. 36.

    Stampe, P., Kolmakova-Partensky, L. and Miller, C., Biophys. J., 62 (1992) 8.

    Google Scholar 

  37. 37.

    Stampe, P., Kolmakova-Partensky, L. and Miller, C., Biochemistry, 33 (1994) 443.

    Google Scholar 

  38. 38.

    Goldstein, S.A.N. and Miller, C., Biophys. J., 62 (1992) 5.

    Google Scholar 

  39. 39.

    Ranganathan, R., Lewis, J.H. and McKinnon, R., Neuron, 16 (1996) 131.

    Google Scholar 

  40. 40.

    Goldstein, S.A.N., Pheasant, D.J. and Miller, C., Neuron, 12 (1994) 1377.

    Google Scholar 

  41. 41.

    Naranjo, D. and Miller, C., Neuron, 16 (1996) 123.

    Google Scholar 

  42. 42.

    Naini, A.A. and Miller, C., Biochemistry, 35 (1996) 6181.

    Google Scholar 

  43. 43.

    Garcia, M.L., Garcia-Calvo, M., Hidalgo, P., Lee, A. and McKinnon, R., Biochemistry, 33 (1994) 6834.

    Google Scholar 

  44. 44.

    Crest, M., Jacquet, G., Gola, M., Zerrouk, H., Benslimane, A., Rochat, H., Mansuelle, P. and Martin-Eauclaire, M.F., J. Biol. Chem., 267 (1992) 1640.

    Google Scholar 

  45. 45.

    Romi, R., Crest, M., Sampieri, F., Jacquet, G., Zerrouk, H., Mansuelle, P., Sorokine, O., Van Dorsselaer, A., Rochat, H., Martin-Eauclaire, M.F. and Van Rietschoten, J., J. Biol. Chem., 268 (1993) 26302.

    Google Scholar 

  46. 46.

    Laraba-Djebari, F., Legros, C., Crest, M., Ceard, B., Romi, R., Mansuelle, P., Jacquet, G., Van Rietschoten, J., Gola, M., Rochat, H., Bougis, P.E. and Martin-Eauclaire, M.F., J. Biol. Chem., 269 (1994) 32835.

    Google Scholar 

  47. 47.

    Gross, A. and McKinnon, R., Neuron, 16 (1996) 399.

    Google Scholar 

  48. 48.

    Hidalgo, P. and McKinnon, R., Science, 268 (1995) 307.

    Google Scholar 

  49. 49.

    Gairi, M., Romi, R., Fernandez, I., Rochat, H., Martin-Eauclaire, M.F., Van Rietschoten, J., Pons, M. and Giralt, E., J. Pept. Sci., 3 (1997) 314.

    Google Scholar 

  50. 50.

    McKinnon, R. and Miller, C., Science, 245 (1989) 1382.

    Google Scholar 

  51. 51.

    McKinnon, R., Heginbotham, L. and Abramson, T., Neuron, 5 (1990) 767.

    Google Scholar 

  52. 52.

    Stocker, M. and Miller, C., Proc. Natl. Acad. Sci. USA, 91 (1994) 9509.

    Google Scholar 

  53. 53.

    Naini, A.A. and Miller, C., Biochemistry, 35 (1996) 6181.

    Google Scholar 

  54. 54.

    Aiyar, J., Rizzi, J.P., Gutman, G.A. and Chandy, K.G., J. Biol. Chem., 271 (1996) 31013.

    Google Scholar 

  55. 55.

    Durell, S.R. and Guy, H.R., Biophys. J., 62 (1992) 238.

    Google Scholar 

  56. 56.

    Yool, A. and Schwarz, T.L., Nature, 349 (1991) 700.

    Google Scholar 

  57. 57.

    Bradley, J.C. and Richards, W.G., Protein Eng., 7 (1993) 859.

    Google Scholar 

  58. 58.

    Haris, P.I., Ramesh, B., Sansom, M.S.P., Kerr, I.D., Srai, K.S. and Chapman, D., Protein Eng. 7 (1994) 255.

    Google Scholar 

  59. 59.

    Heginbotham, L., Lu, Z., Abramson, M. and McKinnon, R., Biophys. J., 66 (1994) 1061.

    Google Scholar 

  60. 60.

    Lu, Q. and Miller, C., Science, 268 (1995) 304.

    Google Scholar 

  61. 61.

    Kürz, L.L., Zühlke, R.D., Zhang, H.J. and Joho, R.H., Biophys. J., 68 (1995) 900.

    Google Scholar 

  62. 62.

    McKinnon, R., Neuron, 14 (1995) 889.

    Google Scholar 

  63. 63.

    Pascual, J.M., Shieh, C.C., Kirsch, G.E. and Brown, A.M., Neuron, 14 (1995) 1055.

    Google Scholar 

  64. 64.

    Guy, H.R. and Durell, S.R., In Farmbrough, D.M. (Ed.), Molecular Evolution of Physiological Processes. Rockefeller University Press, New York, NY, 1994, pp. 197–212.

    Google Scholar 

  65. 65.

    Durell, S.R. and Guy, H.R., Neuropharmacol., 35 (1996) 761.

    Google Scholar 

  66. 66.

    Lipkind, G.M., Hank, D.A. and Fozzard, H.A., Proc. Natl. Acad. Sci. USA, 92 (1995) 9215.

    Google Scholar 

  67. 67.

    Lipkind, G.M. and Fozzard, H.A., J. Membr. Biol., 158 (1997) 187.

    Google Scholar 

  68. 68.

    Kerr, I.D. and Sansom, M.S.P., Biophys. J., 73 (1997) 581.

    Google Scholar 

  69. 69.

    Yang, P.K., Lee, C.Y. and Hwang, M.J., Biophys. J., 72 (1997) 2479.

    Google Scholar 

  70. 70.

    Garcia-Calvo, M., Leonard, R.J., Novick, J., Stevens, S.P., Schmalhofer, W., Kaczorowski, G.J. and Garcia, M.L., J. Biol. Chem., 268 (1993) 18866.

    Google Scholar 

  71. 71.

    Knaus, H.G., Koch, R.O.A., Eberhart, A., Kaczorowski, G.J., Garcia, M.L. and Slaughter, R.S., Biochemistry, 34 (1995) 13627.

    Google Scholar 

  72. 72.

    Rogowski, R.S., Krueger, B.K., Collins, J.H. and Blaustein, M.P., Proc. Natl. Acad. Sci. USA, 91 (1994) 1475.

    Google Scholar 

  73. 73.

    Dauplais, M., Lecoq, A., Song, J., Cotton, J., Jamin, N., Gilquin, B., Roumestand, C., Vita, C., De Medeiros, C.L.C., Rowan, E.G., Harvey, A.L. and Menez, A., J. Biol. Chem., 22 (1997) 4302.

    Google Scholar 

  74. 74.

    Giangiacomo, K.M., Sugg, E.E., Garcia-Calvo, M., Leonarc, R.J., McManus, O.B., Kaczorowski, G.J. and Garcia, M.L., Biochemistry, 32 (1993) 2363.

    Google Scholar 

  75. 75.

    Candia, S., Garcia, M.L. and Latorre, R., Biophys. J., 63 (1992) 583.

    Google Scholar 

  76. 76.

    Fremont, V., Blanc, E., Crest, M., Martin-Eauclaire, M.F., Gola, M., Darbon, H. and Van Rietschoten, J., JIPS (in press).

  77. 77.

    Fernandez, R.R., Romi, R., Szendeffy, S., Martin-Eauclaire, M.F., Rochat, H., Van Rietschoten, J., Pons, M. and Giralt, E., Biochemistry, 33 (1994) 14256.

    Google Scholar 

  78. 78.

    Buisine, E., Wieruszeski, J.M., Lippens, G., Wouters, D., Tartar, A. and Sautière, P., J. Pept. Res., 49 (1997) 545.

    Google Scholar 

  79. 79.

    Gimenez-Gallego, G., Navia, M., Reuben, J.P., Katz, G.M., Kaczorowski, G.J. and Garcia, M.L., Proc. Natl. Acad. Sci. USA, 85 (1988) 3329.

    Google Scholar 

  80. 80.

    Lucchesi, K., Ravindran, A., Young, H. and Moczydlowski, E., J. Membr. Biol., 109 (1989) 269.

    Google Scholar 

  81. 81.

    Romi-Lebrun, R., Lebrun, B., Martin-Eauclaire, M.F., Ishiguro, M., Escoubas, P., Wu, F.Q., Hisada, M., Pongs, O. and Nakajima, T., Biochemistry, 36 (1997) 13473.

    Google Scholar 

  82. 82.

    Galvez, A., Gimenez-Gallego, G., Reuben, J.P., Roy-Constancin, L., Feigenbaum, P., Kaczorowski, G.J. and Garcia, M.L., J. Biol. Chem., 265 (1990) 11083.

    Google Scholar 

  83. 83.

    Legros, C., Oughuideni, R., Darbon, H., Rochat, H., Bougis, P.E. and Martin-Eauclaire, M.F., FEBS Lett., 390 (1996) 81.

    Google Scholar 

  84. 84.

    Garcia, M.L., Garcia-Calvo, M., Hidalgo, P., Lee, A. and McKinnon, R., Biochemistry, 33 (1994) 6834.

    Google Scholar 

  85. 85.

    Possani, L.D., Martin, B.M. and Svendsen, I.B., Carlsberg Res. Commun., 47 (1982) 285.

    Google Scholar 

  86. 86.

    Martin, B.M., Ramirez, A.N., Gurrola, G.B., Nobile, M., Prestipino, G. and Possani, L.D., Biochem. J., 304 (1994) 51.

    Google Scholar 

  87. 87.

    Nieto, A.R., Gurrola, G.B., Vaca, L. and Possani, L.D., Toxicon, 34 (1996) 913.

    Google Scholar 

  88. 88.

    Gomez-Lagunas, F., Olamendi-Portugal, T., Zamudio, F.Z. and Possani, L.D., J. Membr. Biol., 152 (1996) 49.

    Google Scholar 

  89. 89.

    Romi-Lebrun, R., Martin-Eauclaire, M.F., Escoubas, P., Wu, F.Q., Lebrun, B., Hisada, M. and Nakajima, T., Eur. J. Biochem., 245 (1997) 457.

    Google Scholar 

  90. 90.

    Zerrouk, H., Laraba-Djebari, F., Fremont, V., Meki, A., Darbon, H., Mansuelle, P., Oughuideni, R., Van Rietschoten, J., Rochat, H. and Martin-Eauclaire, M.F., Int. J. Pept. Protein Res., 48 (1996) 514.

    Google Scholar 

  91. 91.

    Kharrat, M., Mabrouk, K., Crest, M., Darbon, H., Oughideni, R., Martin-Eauclaire, M.F., Jacquet, G., El Ayeb, M., Van Rietschoten, J., Rochat, H. and Sabatier, J.M., Eur. J. Biochem., 242 (1996) 491.

    Google Scholar 

  92. 92.

    Kraulis, P.J., J. Appl. Crystallogr., 24 (1991) 946.

    Google Scholar 

  93. 93.

    Nicholls, A., Sharp, K.A. and Honig, B.A., Proteins, 11 (1991) 281.

    Google Scholar 

  94. 94.

    Nicholls, A. and Honig, B.A., J. Comp. Chem., 12 (1991) 435.

    Google Scholar 

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Darbon, H., Blanc, E. & Sabatier, JM. Three-dimensional structure of scorpion toxins: Towards a new model of interaction with potassium channels. Perspectives in Drug Discovery and Design 15, 41–60 (1999). https://doi.org/10.1023/A:1017070801207

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  • dipole moment
  • neurotoxin
  • NMR
  • potassium channel
  • scorpion
  • structure