Advertisement

Snaclecs (Snake C-Type Lectins) that Activate Platelets

  • Kenneth J. Clemetson
Chapter

Abstract

One of the major targets for snake venom proteins is haemostasis. This weakens the prey and helps with swallowing and digestion. The venom proteins act either on coagulation factor or on platelets. Snake venom proteins mainly adapt physiological mechanisms to inhibit or activate platelets. The most efficient way for snake venom to reduce platelet function is not by inhibiting the function of individual or several receptors but rather by activating platelets so that they are removed from the circulation producing thrombocytopenia. Platelets can be activated efficiently by an agonist using low molecule numbers in two main ways already used physiologically. One of these is by proteases acting on proteolytically activated receptors. The other major route is by clustering receptors mimicking physiological ligands such as von Willebrand factor and collagen. The snaclecs described in this chapter fall into this latter category. Their targets are those of the physiological ligands and include GPIb, GPVI, α2β1 and the recently discovered CLEC2.

Keywords

Snake Venom Platelet Receptor Washed Platelet Venom Component Sulfated Tyrosine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Batuwangala, T., Leduc, M., Gibbins, J.M., Bon, C., Jones, E.Y., 2004. Structure of the snake-venom toxin convulxin. Acta Crystallogr. D. Biol. Crystallogr. 60, 46–53.PubMedCrossRefGoogle Scholar
  2. Bergmeier, W., Bouvard, D., Eble, J.A., Mokhtari-Nejad, R., Schulte, V., Zirngibl, H., Brakebusch, C., Fassler, R., Nieswandt, B., 2001. Rhodocytin (aggretin) activates platelets lacking α2β1 integrin, GPVI, and the ligand binding domain of GPIbα. J. Biol. Chem. 276, 25121–25126.PubMedCrossRefGoogle Scholar
  3. Brinkhous, K.M., Read, M.S., Fricke, W.A., Wagner, R.H., 1983. Botrocetin (venom coagglutinin): reaction with a broad spectrum of multimeric forms of factor VIII macromolecular complex. Proc. Natl. Acad. Sci. U.S.A. 80, 1463–1466.PubMedCrossRefGoogle Scholar
  4. Chang, C.H., Chung, C.H., Kuo, H.L., Hsu, C.C., Huang, T.F., 2008. The highly specific platelet glycoprotein (GP) VI agonist trowaglerix impaired collagen-induced platelet aggregation ex vivo through matrix metalloproteinase-dependent GPVI shedding. J. Thromb. Haemost. 6, 669–676.PubMedCrossRefGoogle Scholar
  5. Chen, Y.S., Huang, C.H., Chiou, S.H., 2010. Characterization and molecular cloning of one novel C-type lectin from the venom of Taiwan habu (Trimeresurus mucrosquamatus) Toxicon 55, 762–772.PubMedCrossRefGoogle Scholar
  6. Cheng, X., Qian, Y., Liu, Q., Li, B.X., Zhang, M., Liu, J., 1999. Purification, characterization, and cDNA cloning of a new fibrinogenlytic venom protein, Agkisacutacin, from Agkistrodon acutus venom. Biochem. Biophys. Res. Commun. 265, 530–535.PubMedCrossRefGoogle Scholar
  7. Cheng, X., Xu, Z.Y., Liu, Q.D., Li, X.M., Li, X.Y., Liu, J., 2000. Purification and characterization of a platelet agglutinating inhibiting protein (Agkisacutacin) from Agkistrodon acutus venom. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) 32, 653–656.Google Scholar
  8. Chiou, S.H., Huang, K.F., Chow, L.P., Tsugita, A., Wu, S.H., 1996. Isolation of a venom factor devoid of proteolytic activity from Taiwan habu (Trimeresurus mucrosquamatus): N-terminal sequence homology and no functional similarity to factors IX/X-binding proteins and botrocetin. J. Protein Chem. 15, 667–674.PubMedCrossRefGoogle Scholar
  9. Chung, C.H., Au, L.C., Huang, T.F., 1999. Molecular cloning and sequence analysis of aggretin, a collagen-like platelet aggregation inducer. Biochem. Biophys. Res. Commun. 263, 723–727.PubMedCrossRefGoogle Scholar
  10. Clemetson, K.J., Morita, T., Kini, R.M., 2009. Scientific and standardization committee communications: classification and nomenclature of snake venom C-type lectins and related proteins. J. Thromb. Haemost. 7, 360.PubMedCrossRefGoogle Scholar
  11. Dormann, D., Clemetson, J.M., Navdaev, A., Kehrel, B.E., 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
  12. Du, X.Y., Clemetson, J.M., Navdaev, A., Magnenat, E.M., Wells, T N., Clemetson, K.J., 2002a. Ophioluxin, a convulxin-like C-type lectin from Ophiophagus hannah (King cobra) is a powerful platelet activator via glycoprotein VI. J. Biol. Chem. 277, 35124–35132.PubMedCrossRefGoogle Scholar
  13. Du, X.Y., Magnenat, E., Wells, T.N., Clemetson, K.J., 2002b. Alboluxin, a snake C-type lectin from Trimeresurus albolabris venom is a potent platelet agonist acting via GPIb and GPVI. Thromb. Haemost. 87, 692–698.Google Scholar
  14. Du, X.Y., Navdaev, A., Clemetson, J.M., Magnenat, E., Wells, T.N., Clemetson, K.J., 2001. Bilinexin, a snake C-type lectin from Agkistrodon bilineatus venom agglutinates platelets via GPIb and α2β1. Thromb. Haemost. 86, 1277–1283.PubMedGoogle Scholar
  15. Flood, V.H., Friedman, K.D., Gill, J.C., Morateck, P.A., Wren, J.S., Scott, J.P., Montgomery, R.R., 2009. Limitations of the ristocetin cofactor assay in measurement of von Willebrand factor function. J. Thromb. Haemost. 7, 1832–1839.PubMedCrossRefGoogle Scholar
  16. Fry, B.G., Vidal, N., Norman, J.A., Vonk, F.J., Scheib, H., Ramjan, S.F., Kuruppu, S., Fung, K., Hedges, S.B., Richardson, M.K., Hodgson, W.C., Ignjatovic, V., Summerhayes, R., Kochva, E., 2006. Early evolution of the venom system in lizards and snakes. Nature 439, 584–588.PubMedCrossRefGoogle Scholar
  17. Fukuda, K., Doggett, T., Laurenzi, I.J., Liddington, R.C., Diacovo, T.G. 2005. The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation. Nat. Struct. Mol. Biol. 12, 152–159.PubMedCrossRefGoogle Scholar
  18. Fukuda, K., Doggett, T.A., Bankston, L.A., Cruz, M.A., Diacovo, T.G., Liddington, R.C., 2002. Structural basis of von Willebrand factor activation by the snake toxin botrocetin. Structure 10, 943–950.PubMedCrossRefGoogle Scholar
  19. Fukuda, K., Mizuno, H., Atoda, H., Morita, T., 2000. Crystal structure of flavocetin-A, a platelet glycoprotein Ib-binding protein, reveals a novel cyclic tetramer of C-type lectin-like heterodimers. Biochemistry 39, 1915–1923.PubMedCrossRefGoogle Scholar
  20. Hamako, J., Matsui, T., Suzuki, M., Ito, M., Makita, K., Fujimura, Y., Ozeki, Y., Titani, K., 1996. Purification and characterization of bitiscetin, a novel von Willebrand factor modulator protein from Bitis arietans snake venom. Biochem. Biophys. Res. Commun. 226, 273–279.PubMedCrossRefGoogle Scholar
  21. Hirotsu, S., Mizuno, H., Fukuda, K., Qi, M.C., Matsui, T., Hamako, J., Morita, T., Titani, K., 2001. Crystal structure of bitiscetin, a von Willebrand factor-dependent platelet aggregation inducer. Biochemistry 40, 13592–13597.PubMedCrossRefGoogle Scholar
  22. Hooley, E., Papagrigoriou, E., Navdaev, A., Pandey, A.V., Clemetson, J.M., Clemetson, K.J., Emsley, J., 2008. The crystal structure of the platelet activator aggretin reveals a novel (αβ)2 dimeric structure. Biochemistry 47, 7831–7837.PubMedCrossRefGoogle Scholar
  23. Horii, K., Brooks, M.T., Herr, A.B., 2009. Convulxin forms a dimer in solution and can bind eight copies of glycoprotein VI: implications for platelet activation. Biochemistry 48, 2907–2914.PubMedCrossRefGoogle Scholar
  24. Howard, M.A. and Firkin, B.G., 1971. Ristocetin – a new tool in the investigation of platelet aggregation. Thromb. Diath. Haemorrh. 26, 362–369.PubMedGoogle Scholar
  25. Huang, K.F., Ko, T.P., Hung, C.C., Chu, J., Wang, A.H., Chiou, S.H., 2004. Crystal structure of a platelet-agglutinating factor isolated from the venom of Taiwan habu (Trimeresurus mucrosquamatus). Biochem. J. 378, 399–407.PubMedCrossRefGoogle Scholar
  26. Kanaji, S., Kanaji, T., Furihata, K., Kato, K., Ware, J.L., Kunicki, T.J. 2003. Convulxin binds to native, human glycoprotein Ibα (GPIbα). J. Biol. Chem. 278, 39452–39460.PubMedCrossRefGoogle Scholar
  27. Kaneko, M.K., Kato, Y., Kameyama, A., Ito, H., Kuno, A., Hirabayashi, J., Kubota, T., Amano, K., Chiba, Y., Hasegawa, Y., Sasagawa, I., Mishima, K., Narimatsu, H., 2007. Functional glycosylation of human podoplanin: glycan structure of platelet aggregation-inducing factor. FEBS Lett. 581, 331–336.PubMedCrossRefGoogle Scholar
  28. Kato, Y., Kaneko, M.K., Kunita, A., Ito, H., Kameyama, A., Ogasawara, S., Matsuura, N., Hasegawa, Y., Suzuki-Inoue, K., Inoue, O., Ozaki, Y., Narimatsu, H., 2008. Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Cancer Sci. 99, 54–61.PubMedGoogle Scholar
  29. Kerrigan, A.M., Dennehy, K.M., Mourão-Sá, D., Faro-Trindade, I., Willment, J.A., Taylor, P.R., Eble, J.A., Reis e Sousa, C., Brown, G.D., 2009. CLEC-2 is a phagocytic activation receptor expressed on murine peripheral blood neutrophils. J. Immunol. 182, 4150–4157.PubMedCrossRefGoogle Scholar
  30. Kowalska, M.A., Tan, L., Holt, J.C., Peng, M., Karczewski, J., Calvete, J.J., Niewiarowski, S., 1998. Alboaggregins A and B. Structure and interaction with human platelets. Thromb. Haemost. 79, 609–613.PubMedGoogle Scholar
  31. Kunita, A., Kashima, T.G., Morishita, Y., Fukayama, M., Kato, Y., Tsuruo, T., Fujita, N., 2007. The platelet aggregation-inducing factor aggrus/podoplanin promotes pulmonary metastasis. Am. J. Pathol. 170, 1337–1347.PubMedCrossRefGoogle Scholar
  32. Leduc, M., Bon, C., 1998. Cloning of subunits of convulxin, a collagen-like platelet-aggregating protein from crotalus durissus terrificus venom. Biochem. J. 333, 389–393.PubMedGoogle Scholar
  33. Lee, W.H., Du, X.Y., Lu, Q.M., Clemetson, K.J., Zhang, Y., 2003. Stejnulxin, a novel snake C-type lectin-like protein from Trimeresurus stejnegeri venom is a potent platelet agonist acting specifically via GPVI. Thromb. Haemost. 90, 662–671.PubMedGoogle Scholar
  34. Li, X., Zheng, L., Kong, C., Kolatkar, P.R., Chung, M.C., 2004. Purpureotin: a novel di-dimeric C-type lectin-like protein from Trimeresurus purpureomaculatus venom is stabilized by noncovalent interactions. Arch. Biochem. Biophys. 424, 53–62.PubMedCrossRefGoogle Scholar
  35. Liu, S., Zhu, Z., Sun, J., Huang, Q., Teng, M., Niu, L., 2002. Purification, crystallization and preliminary X-ray crystallographic analysis of agkaggregin, a C-type lectin-like protein from Agkistrodon acutus venom. Acta Crystallogr. D. Biol. Crystallogr. 58, 675–678.PubMedCrossRefGoogle Scholar
  36. Lu, Q., Navdaev, A., Clemetson, J.M., Clemetson, K.J., 2004. GPIb is involved in platelet aggregation induced by mucetin, a snake C-type lectin protein from Chinese habu (Trimeresurus mucrosquamatus) venom. Thromb. Haemost. 91, 1168–1176.PubMedGoogle Scholar
  37. Maita, N., Nishio, K., Nishimoto, E., Matsui, T., Shikamoto, Y., Morita, T., Sadler, J.E., Mizuno, H., 2003. Crystal structure of von Willebrand factor A1 domain complexed with snake venom, bitiscetin: insight into glycoprotein Ibα binding mechanism induced by snake venom proteins. J. Biol. Chem. 278, 37777–37781.PubMedCrossRefGoogle Scholar
  38. Mizuno, H., Fujimoto, Z., Atoda, H., Morita, T., 2001. Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X. Proc. Natl. Acad. Sci. U.S.A. 98, 7230–7234.PubMedCrossRefGoogle Scholar
  39. Mizuno, H., Fujimoto, Z., Koizumi, M., Kano, H., Atoda, H., Morita, T., 1999. Crystal structure of coagulation factor IX-binding protein from habu snake venom at 2.6 Å: implication of central loop swapping based on deletion in the linker region. J. Mol. Biol. 289, 103–112.PubMedCrossRefGoogle Scholar
  40. Murakami, M.T., Zela, S.P., Gava, L.M., Michelan-Duarte, S., Cintra, A.C., Arni, R.K., 2003. Crystal structure of the platelet activator convulxin, a disulfide-linked α4β4 cyclic tetramer from the venom of Crotalus durissus terrificus. Biochem. Biophys. Res. Commun. 310, 478–482.PubMedCrossRefGoogle Scholar
  41. Navdaev, A., Clemetson, J.M., Polgar, J., Kehrel, B.E., Glauner, M., Magnenat, E., Wells, T.N., Clemetson, K.J., 2001. Aggretin, a heterodimeric C-type lectin from Calloselasma rhodostoma (Malayan pit viper) stimulates platelets by binding to α2β1 integrin and GPIb, activating Syk and PLCγ2, but does not involve the GPVI/Fcγ collagen receptor. J. Biol. Chem. 276, 20882–20889.PubMedCrossRefGoogle Scholar
  42. Navdaev, A., Dormann, D., Clemetson, J.M., Clemetson, K.J., 2001. Echicetin, a GPIb-binding snake C-type lectin from Echis carinatus, also contains a binding site for IgMκ responsible for platelet agglutination in plasma and inducing signal transduction. Blood 97, 2333–2341.PubMedCrossRefGoogle Scholar
  43. Peng, M., Holt, J.C., Niewiarowski, S., 1994. Isolation, characterization and amino acid sequence of echicetin β-subunit, a specific inhibitor of von Willebrand factor and thrombin interaction with glycoprotein Ib. Biochem. Biophys. Res. Commun. 205, 68–72.PubMedCrossRefGoogle Scholar
  44. Peng, M., Lu, W., Kirby, E.P., 1991. Alboaggregin-B: A new platelet agonist that binds to platelet membrane glycoprotein Ib. Biochemistry 30, 11529–11536.PubMedCrossRefGoogle Scholar
  45. Peng, M., Lu, W., Kirby, E.P., 1992. Characterization of three alboaggregins purified from Trimeresurus albolabris venom. Thromb. Haemost. 67, 702–707.PubMedGoogle Scholar
  46. Polgar, J., Clemetson, J.M., Kehrel, B.E., Wiedemann, M., Magnenat, E.M., Wells, T.N.C., Clemetson, K.J., 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, 13576–13583.PubMedCrossRefGoogle Scholar
  47. Polgar, J., Magnenat, E.M., Peitsch, M.C., Wells, T.N., Saqi, M.S., Clemetson, K.J., 1997. Amino acid sequence of the alpha subunit and computer modelling of the alpha and beta subunits of echicetin from the venom of Echis carinatus (saw-scaled viper). Biochem. J. 323, 533–537.PubMedGoogle Scholar
  48. Rucavado, A., Soto, M., Kamiguti, A.S., Theakston, R.D., Fox, J.W., Escalante, T., Gutierrez, J.M., 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
  49. Sakurai, Y., Fujimura, Y., Kokubo, T., Imamura, K., Kawasaki, T., Handa, M., Suzuki, M., Matsui, T., Titani, K., Yoshioka, A., 1998. The cDNA cloning and molecular characterization of a snake venom platelet glycoprotein Ib-binding protein, mamushigin, from Agkistrodon halys blomhoffii venom. Thromb. Haemost. 79, 1199–1207.PubMedGoogle Scholar
  50. Sen, U., Vasudevan, S., Subbarao, G., McClintock, R.A., Celikel, R., Ruggeri, Z.M., Varughese, K.I., 2001. Crystal structure of the von Willebrand factor modulator botrocetin. Biochemistry 40, 345–352.PubMedCrossRefGoogle Scholar
  51. Shin, Y., Okuyama, I., Hasegawa, J., Morita, T., 2000. Molecular cloning of glycoprotein Ib-binding protein, flavocetin-A, which inhibits platelet aggregation. Thromb. Res. 99, 239–247.PubMedCrossRefGoogle Scholar
  52. Suzuki-Inoue, K., Fuller, G.L., García, A., Eble, J.A., Pöhlmann, S., Inoue, O., Gartner, T.K., Hughan, S.C., Pearce, A.C., Laing, G.D., Theakston, R.D., Schweighoffer, E., Zitzmann, N., Morita, T., Tybulewicz, V.L., Ozaki, Y., Watson, S.P., 2006. A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2. Blood 107, 542–549.PubMedCrossRefGoogle Scholar
  53. Taniuchi, Y., Kawasaki, T., Fujimura, Y., Suzuki, M., Titani, K., Sakai, Y., Kaku, S., Hisamichi, N., Satoh, N., Takenaka, T., Handa, M., Sawai, Y., 1995. Flavocetin-A and -B, two high molecular mass glycoprotein Ib binding proteins with high affinity purified from Trimeresurus flavoviridis venom, inhibit platelet aggregation at high shear stress. Biochim. Biophys. Acta 1244, 331–338.PubMedCrossRefGoogle Scholar
  54. Uhrin, P., Zaujec, J., Breuss, J.M., Olcaydu, D., Chrenek, P., Stockinger, H., Fuertbauer, E., Moser, M., Haiko, P., Fässler, R., Alitalo, K., Binder, B.R., Kerjaschki, D., 2010. Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation. Blood 115, 3997–4005.Google Scholar
  55. Usami, Y., Fujimura, Y., Suzuki, M., Ozeki, Y., Nishio, K., Fukui, H., Titani, K., 1993. Primary structure of two-chain botrocetin, a von Willebrand factor modulator purified from the venom of Bothrops jararaca. Proc. Natl. Acad. Sci. U.S.A. 90, 928–932.PubMedCrossRefGoogle Scholar
  56. Valentin, E., Lambeau, G., 2000. What can venom phospholipases A2 tell us about the functional diversity of mammalian secreted phospholipases A2? Biochimie 82, 815–831.PubMedCrossRefGoogle Scholar
  57. Wang, R., Kong, C., Kolatkar, P., Chung, M.C., 2001. A novel dimer of a C-type lectin-like heterodimer from the venom of Calloselasma rhodostoma (Malayan pit viper). FEBS Lett. 508, 447–453.PubMedCrossRefGoogle Scholar
  58. Wang, W.J., Huang, T.F., 2001. A novel tetrameric venom protein, agglucetin from Agkistrodon acutus, acts as a glycoprotein Ib agonist. Thromb. Haemost. 86, 1077–1086.PubMedGoogle Scholar
  59. Wei, Q., Lu, Q.M., Jin, Y., Li, R., Wei, J.F., Wang, W.Y., Xiong, Y.L., 2002. Purification and cloning of a novel C-type lectin-like protein with platelet aggregation activity from Trimeresurus mucrosquamatus venom. Toxicon. 40, 1331–1338.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Department of HaematologyUniversity of Berne, InselspitalBerneSwitzerland

Personalised recommendations