Snake Venom Toxins Affecting Platelet Function

  • Robert K. Andrews
  • Elizabeth E. Gardiner
  • Michael C. Berndt
Part of the Methods in Molecular Biology™ book series (MIMB, volume 273)

Abstract

Botrocetin from the South American pit viper Bothrops jararaca was described as an activator of von Willebrand factor-dependent platelet aggregation by Read, Shermer, and Brinkhous in 1978 (1). Subsequently, botrocetin has been widely used as an important in vitro modulator in the analysis of von Willebrand factor and platelet aggregation. Botrocetin has since been identified as a heterodimer of the C-type lectin family of snake venom proteins (∼25 kDa nonreduced, ∼14 kDa reduced), the primary sequence and crystal structure have been determined, and specific binding sites within the A1 domain of von Willebrand factor have been identified (2, 3, 4, 5, 6, 7, 8). Interestingly, members of the metalloproteinase-disintegrin family of snake venom proteins—jararhagin, jaracetin, and one-chain botrocetin—are functionally related to two-chain botrocetin, and also interact with the von Willebrand factor A1 domain (4,9,10). Jaracetin and one-chain botrocetin are variably processed forms of jararhagin and are found in the same viper species as the C-type lectin family, two-chain botrocetin. In this regard, recent evidence suggests that C-type lectin proteins and metalloproteinase-disintegrins may be derived from a common gene encoding a much larger precursor protein (11).

Keywords

Carbide EDTA Tyrosine Citrate Electrophoresis 

References

  1. 1.
    Read, M. S., Shermer, R. W., and Brinkhous, K. M. (1978) Venom coagglutinin: an activator of platelet aggregation dependent on von Willebrand Factor. Proc. Natl. Acad. Sci. USA 83, 514–4518.Google Scholar
  2. 2.
    Andrews, R. K., Booth, W. J., Gorman, J. J., Castaldi, P. A., and Berndt, M. C. (1989) Purification of botrocetin from Bothrops jararaca venom. Analysis of the botrocetin-mediated interaction between von Willebrand factor and the human platelet membrane glycoprotein Ib–IX complex. Biochemistry 28, 8317–8326.PubMedCrossRefGoogle Scholar
  3. 3.
    Shen, Y., Romo, G. M., Dong, J.-F., Schade, A., McIntire, L. V., Kenny, D., et al. (2000) Requirement of leucine-rich repeats of GP Ibα for shear-dependent and static binding of von Willebrand factor to the platelet membrane GP Ib-IX-V complex. Blood 95, 903–910.PubMedGoogle Scholar
  4. 4.
    Fujimura, Y., Titani, K., Usami, Y., Suzuki, M., Oyama, R., Matsui, T., et al. (1991) Isolation and chemical characterization of two structurally and functionally distinct forms of botrocetin, the platelet coagglutinin isolated from the venom of Bothrops jararaca. Biochemistry 30, 1957–1964.PubMedCrossRefGoogle Scholar
  5. 5.
    Berndt, M. C., Ward, C. M., Booth, W. J., Castaldi, P. A., Mazurov, A. V., and Andrews, R. K. (1992) Identification of aspartic acid 514 through glutamic acid 542 as a glycoprotein Ib–IX complex receptor recognition sequence in von Willebrand factor. Mechanism of modulation of von Willebrand factor by ristocetin and botrocetin. Biochemistry 31, 11,144–11,151.PubMedCrossRefGoogle Scholar
  6. 6.
    Usami, Y., Fujimura, Y., Suzuki, M., Ozeki, Y., Nishio, K., Fukui, H., et al. (1993) Primary structure of two-chain botrocetin; a von Willebrand factor modulator purified from the venom of Bothrops jararaca. Proc. Natl. Acad. Sci. USA 90, 928–932.PubMedCrossRefGoogle Scholar
  7. 7.
    Sen, U., Vasudevan, S., Subbarao, G., McClintock, R. A., Celikel, R., Ruggeri, Z. M., et al. (2001) Crystal structure of the von Willebrand factor modulator botrocetin. Biochemistry 40, 345–352.PubMedCrossRefGoogle Scholar
  8. 8.
    Fukuda, K., Doggett, T. A., Bankston, L. A., Cruz, M. A., Diacovo, T. G., and Liddington, R. C. (2002) Structural basis of von Willebrand factor activation by the snake toxin botrocetin. Structure (Camb) 10, 943–950.CrossRefGoogle Scholar
  9. 9.
    De Luca, M., Ward, C. M., Ohmori, K., Andrews, R. K., and Berndt, M. C. (1995) Jarar-hagin and jaracetin: novel snake venom inhibitors of the integrin collagen receptor, α2β1. Biochem. Biophys. Res. Commun. 206, 570–576.PubMedCrossRefGoogle Scholar
  10. 10.
    Paine, M. J. I., Desmond, H. P., Theakston, R. D. G, and Crampton, J. M. (1992) Purification, cloning, and molecular characterization of a high molecular weight hemorrhagic metalloprotease, jararhagin, from Bothrops jararaca venom: insights into the disintegrin gene family. J. Biol. Chem. 267, 22,869–22,876.PubMedGoogle Scholar
  11. 11.
    Kini, R. M. (1996) Are C-type lectin-related proteins derived by proteolysis of metalloproteinase/disintegrin precursor proteins? Toxicon 34, 1287–1294.PubMedCrossRefGoogle Scholar
  12. 12.
    Obert, B., Houllier, A., Meyer, D., and Girma, J.-P. (1999) Conformational changes in the A3 domain of von Willebrand factor modulate the interaction of the A1 domain with platelet glycoprotein Ib. Blood 93, 1959–1968.PubMedGoogle Scholar
  13. 13.
    Andrews, R. K., Kroll, M. H., Ward, C. M., Rose, J. W., Scarborough, R. M., Smith, A. I., et al. (1996) Binding of a novel 50-kilodalton alboaggregin from Trimeresurus albolabris and related viper venom proteins to the platelet membrane glycoprotein Ib-IX–V complex. Effect on platelet aggregation and glycoprotein Ib-mediated platelet activation. Biochemistry 35, 12,629–12,639.PubMedCrossRefGoogle Scholar
  14. 14.
    Jandrot-Perrus, M., Lagrue, A. H., Okuma, M., and Bon, C. (1997) Adhesion and activation of human platelets induced by convulxin involve glycoprotein VI and integrin α2β1. J. Biol. Chem. 272, 27,035–27,041.PubMedCrossRefGoogle Scholar
  15. 15.
    Polgar, J., Clemetson, J. M., Kehrel, B. E., Weidemann, M., Magnenat, E. M., Wells, T. N. C., et al. (1997) Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor. J. Biol. Chem. 272, 13,576–13,583.PubMedCrossRefGoogle Scholar
  16. 16.
    Du, X.-Y., Clemetson, J. M., Navdaev, A., Magnenat, E. M., Wells, T. N. C, and Clemetson, K. J. (2002) Ophioluxin, a convulxin-like C-type lectin from Ophiophagus hannah (King cobra) is a powerful platelet activator via glycoprotein VI. J. Biol. Chem. 277, 35,124–35,132.PubMedCrossRefGoogle Scholar
  17. 17.
    Andrews, R. K., Gardiner, E. E., Asazuma, N., Berlanga, O., Tulasne, D., Nieswandt, B., et al. (2001) A novel viper venom metalloproteinase, alborhagin, is an agonist at the platelet collagen receptor GPVI. J. Biol. Chem. 276, 28,092–28,097.PubMedCrossRefGoogle Scholar
  18. 18.
    De Luca, M., Dunlop, L. C, Andrews, R. K., Flannery, J. V., Ettling, R., Cumming, D. A., et al. (1995) A novel cobra venom metalloproteinase, mocarhagin, cleaves a ten amino acid peptide from the mature N-terminus of P-selectin glycoprotein ligand receptor, PSGL-1, and abolishes P-selectin binding. J. Biol. Chem. 270, 26,734–26,737.PubMedCrossRefGoogle Scholar
  19. 19.
    Ward, C. M., Andrews, R. K., Smith, A. I., and Berndt, M. C. (1996) Mocarhagin, a novel cobra venom metalloproteinase, cleaves the platelet von Willebrand factor receptor glycoprotein Ibα. Identification of the sulfated tyrosine/anionic sequence Tyr-276-Glu-282 of glycoprotein Ibα as a binding site for von Willebrand factor and α-thrombin. Biochemistry 35, 4929–4938.PubMedCrossRefGoogle Scholar
  20. 20.
    Kamiguti, A. S., Hay, C. R. M., and Zuzel, M. (1996) Inhibition of collagen-induced platelet aggregation as the result of cleavage of α2β1-integrin by the snake venom metalloproteinase jararhagin. Biochem. J. 320, 635–641.PubMedGoogle Scholar
  21. 21.
    Hamako, J., Matsui, T., Nishida, S., Nomura, S., Fujimura, Y., Ito, M., et al. (1998) Purification and characterization of kaouthiagin, a von Willebrand factor-binding and-cleaving metalloproteinase from Naja kaouthia cobra venom. Thromb. Haemost. 80, 499–505.PubMedGoogle Scholar
  22. 22.
    Wu, W. B., Peng, H. C., and Huang, T.-F. (2001) Crotalin, a vWF and GP Ib cleaving metalloproteinase from venom of Crotalus atrox. Thromb. Haemost. 86, 1501–1511.PubMedGoogle Scholar
  23. 23.
    Zhou, Q., Dangelmaier, C., and Smith, J. B. (1996) The hemorrhagin catrocollastatin inhibits collagen-induced platelet aggregation by binding to collagen via its disintegrin-like domain. Biochem. Biophys. Res. Commun. 219, 720–726.PubMedCrossRefGoogle Scholar
  24. 24.
    Andrews, R. K. and Berndt, M. C. (2000) Snake venom modulators of platelet adhesion receptors and their ligands. Toxicon 38, 775–791.PubMedCrossRefGoogle Scholar
  25. 25.
    Andrews, R. K., Kamiguti, A., Berlanga, O., Leduc, M., Theakston, R. D. G., and Watson, S. P. (2001) The use of snake venom toxins as tools to study the platelet receptors for collagen and von Willebrand factor. Haemostasis 31, 155–172.PubMedGoogle Scholar
  26. 26.
    Fujimura, Y., Kawasaki, T., and Titani, K. (1996) Snake venom proteins modulating the interaction between von Willebrand factor and platelet glycoprotein Ib. Thromb. Haemost. 76, 633–639.PubMedGoogle Scholar
  27. 27.
    Dormann, D., Clemetson, J. M., Navdaev, A., Kehrel, B. E., and Clemetson, K. J. (2001) Alboaggregin A activates platelets by a mechanism involving glycoprotein VI as well as glycoprotein Ib. Blood 97, 929–936.PubMedCrossRefGoogle Scholar
  28. 28.
    Asazuma, N., Marshall, S., Berlanga, O., Snell, D., Poole, A., Berndt, M. C., et al. (2001) The snake venom toxin alboaggregin-A activates GPVI. Blood 97, 3989–3991PubMedCrossRefGoogle Scholar
  29. 29.
    Kuter, D. J., Gminski, D., and Rosenberg, R. D. (1992) Botrocetin agglutination of rat megakaryocytes: a rapid method for megakaryocyte isolation. Exp. Hematol. 20, 1085–1089.PubMedGoogle Scholar
  30. 30.
    Berlanga, O., Bobe, R., Becker, M., Murphy, G., Leduc, M., Bon, C., et al. (2000) Expression of the collagen receptor glycoprotein VI during megakaryocyte differentiation. Blood 96, 2740–2745.PubMedGoogle Scholar
  31. 31.
    Ward, C. M., Vinogradov, D. V., Andrews, R. K., and Berndt, M. C. (1996) Characterization of mocarhagin, a cobra venom metalloproteinase from Naja mocambique mocambique, and related proteins from other Elapidae venoms. Toxicon 34, 1203–1206.PubMedCrossRefGoogle Scholar
  32. 32.
    Rucavado, A., Soto, M., Kamiguti, A. S., Theakston, R. D., Fox, J. W., Escalante, T., et al. (2001) Characterization of aspercetin, a platelet aggregating component from the venom of the snake Bothrops asper which induces thrombocytopenia and potentiates metalloproteinase-induced hemorrhage. Thromb. Haemost. 85, 710–715.PubMedGoogle Scholar
  33. 33.
    Dong, J.-F., Berndt, M. C., Schade, A., McIntire, L. V., Andrews, R. K., and López, J. A. (2001) Ristocetin-but not botrocetin-dependent binding of von Willebrand factor to the platelet membrane glycoprotein Ib-IX-V complex correlates with shear-dependent interactions. Blood 97, 162–168.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Robert K. Andrews
    • 1
  • Elizabeth E. Gardiner
    • 1
  • Michael C. Berndt
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyMonash UniversityClaytonAustralia

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