Scorpion Venom Research Around the World: Tityus serrulatus

  • Karla de Castro Figueiredo Bordon
  • Camila Takeno Cologna
  • Eliane Candiani Arantes
Living reference work entry


Tityus serrulatus is considered the most dangerous scorpion in Brazil. It is widely distributed, especially in the Southeast region, and is responsible for the highest number and most severe accidents. This chapter focuses on Tityus serrulatus scorpion venom (Tsv) and aspires to unravel its complex composition with emphases on its isolated proteins, their targets, structures, and functions. It takes a closer look at the peptides related to the Na+ and K+ channel toxin families, NaTx and KTx, respectively, including their toxin precursors. Additionally, a hyaluronidase, a serine proteinase, metalloproteinases, and many other proteins/peptides, such as a nontoxic protein (Ts4), PAPE peptides, bradykinin-potentiating peptides (BPP), antimicrobial peptides (AMP), anionic peptides, and venom peptides with undetermined functions, were reported.


Disulfide Bridge Venom Gland Scorpion Venom Scorpion Toxin Scorpion Sting 
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.


  1. Almeida FM, Pimenta AMC, De Figueiredo SG, Santoro MM, Martin-Eauclaire MF, Diniz CR, et al. Enzymes with gelatinolytic activity can be found in Tityus bahiensis and Tityus serrulatus venoms. Toxicon. 2002;40(7):1041–5.PubMedCrossRefGoogle Scholar
  2. Alvarenga ÉR, Mendes TM, Magalhães BF, Siqueira FF, Dantas AE, Barroca TM, et al. Transcriptome analysis of the Tityus serrulatus scorpion venom gland. Open J Genet. 2012;2:210–20.CrossRefGoogle Scholar
  3. Arantes EC, Prado WA, Sampaio SV, Giglio JR. A simplified procedure for the fractionation of Tityus serrulatus venom – isolation and partial characterization of TsTX-IV, a new neurotoxin. Toxicon. 1989;27(8):907–16.PubMedCrossRefGoogle Scholar
  4. Banerjee A, Lee A, Campbell E, MacKinnon R. Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel. eLife. 2013;2:e00594.PubMedCentralPubMedCrossRefGoogle Scholar
  5. Barhanin J, Giglio JR, Leopold P, Schmid A, Sampaio SV, Lazdunski M. Tityus serrulatus venom contains two classes of toxins: Tityus ‘gamma’ toxin is a new tool with a very high affinity for studying the Na+ channel. J Biol Chem. 1982;257(21):2553–8.Google Scholar
  6. Bechis G, Sampieri F, Yuan PM, Brando T, Martin MF, Diniz CR, Rochat H. Amino acid sequence of toxin VII, a β-toxin from the venom of the scorpion Tityus serrulatus. Biochem Biophys Res Commun. 1984;122:1146–53.PubMedCrossRefGoogle Scholar
  7. Bergeron ZL, Bingham J-P. Scorpion toxins specific for potassium (K+) channels: a historical overview of peptide bioengineering. Toxins. 2012;4(11):1082–119.PubMedCentralPubMedCrossRefGoogle Scholar
  8. Bertazzi DT. Isolation and biochemical characterization of components from Tityus serrulatus venom with action on the complement system. Ribeirão Preto: University of São Paulo; 2007.Google Scholar
  9. Bitencourt CS, Pereira PA, Ramos SG, Sampaio SV, Arantes EC, Aronoff DM, et al. Hyaluronidase recruits mesenchymal-like cells to the lung and ameliorates fibrosis. Fibrogenesis Tissue Repair. 2011;4(1):3.PubMedCentralPubMedCrossRefGoogle Scholar
  10. Blanc E, Lecomte C, VanRietschoten J, Sabatier JM, Darbon H. Solution structure of TsKapa, a charybdotoxin-like scorpion toxin from Tityus serrulatus with high affinity for apamin-sensitive Ca2+-activated K+ channels. Prot Struct Funct Genet. 1997;29(3):359–69.CrossRefGoogle Scholar
  11. Bordon KCF, Cologna CT, Tytgat J, Arantes EC. Purification and characterization of Ts16, new specific Kv1.2 blocker, from Tityus serrulatus scorpion venom. In: Calvete JJ, chairman. Proceedings of the 17th Congress of the European Section of the International Society of Toxinology; 2011 Sep 11–15; Valencia: Program & Abstracts Book, p. 240, Poster 128; 2011.Google Scholar
  12. Bosmans F, Martin-Eauclaire MR, Tytgat J. Differential effects of five ‘classical’ scorpion β-toxins on rNav1.2a and DmNav1 provide clues on species-selectivity. Toxicol Appl Pharmacol. 2007;218:45–51.Google Scholar
  13. Bosmans F, Martin- Eauclaire MF, Swartz KJ. Deconstructing voltage sensor function and pharmacology in sodium channels. Nature. 2008;456:202–8.PubMedCentralPubMedCrossRefGoogle Scholar
  14. Bosmans F, Puopolo M, Martin-Eauclaire MF, Bean BP, Swartz KJ. Functional properties and toxin pharmacology of a dorsal root ganglion sodium channel viewed through its voltage sensors. J Gen Physiol. 2011;138:59–72.PubMedCentralPubMedCrossRefGoogle Scholar
  15. Campos FV, Coronas FIV, Beirao PSL. Voltage-dependent displacement of the scorpion toxin Ts3 from sodium channels and its implication on the control of inactivation. Br J Pharmacol. 2004;142(7):1115–22.PubMedCentralPubMedCrossRefGoogle Scholar
  16. Campos FV, Chanda B, Beirao PS, Bezanilla F. β-Scorpion toxin modifies gating transitions in all four voltage sensors of the sodium channel. J Gen Physiol. 2007;130:257–68.PubMedCentralPubMedCrossRefGoogle Scholar
  17. Campos FV, Chanda B, Beirao PS, Bezanilla F. α-Scorpion toxin impairs a conformational change that leads to fast inactivation of muscle sodium channels. J Gen Physiol. 2008;132:251–63.PubMedCentralPubMedCrossRefGoogle Scholar
  18. Carmanhan PAS, Bordon KCF, Arantes EC. Isolation and characterization of a new probable potassium channel toxin from Tityus serrulatus venom. 2013;UniProtKB: P86822.Google Scholar
  19. Catterall WA, Cestele S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T. Voltage-gated ion channels and gating modifier toxins. Toxicon. 2007;49(2):124–41.PubMedCrossRefGoogle Scholar
  20. Cecchini AL, Vasconcelos F, Amara SG, Giglio JR, Arantes EC. Effects of Tityus serrulatus scorpion venom and its toxin TsTX-V on neurotransmitter uptake in vitro. Toxicol Appl Pharmacol. 2006;217(2):196–203.PubMedCrossRefGoogle Scholar
  21. Cerni FA, Amorim FG, Bordon KCF, Arantes EC. Isolation and electrophysiological characterization of a new potassium channel blocker from Tityus serrulatus venom. 2013;UniProtKB: P86822.Google Scholar
  22. Chávez-Olórtegui C, Kalapothakis E, Ferreira A, Ferreira AP, Diniz CR. Neutralizing capacity of antibodies elicited by a non-toxic protein purified from the venom of the scorpion Tityus serrulatus. Toxicon. 1997;35(2):213–21.PubMedCrossRefGoogle Scholar
  23. Chávez-Olórtegui C, Molina F, Granier C. Molecular basis for the cross-reactivity of antibodies elicited by a natural anatoxin with alpha- and beta-toxins from the venom of Tityus serrulatus scorpion. Mol Immunol. 2002;38(11):867–76.PubMedCrossRefGoogle Scholar
  24. Coelho VA, Cremonez CM, Anjolette FAP, Aguiar JF, Varanda WA, Arantes EC. Functional and structural study comparing the C-terminal amidated β-neurotoxin Ts1 with its isoform Ts1-G isolated from Tityus serrulatus venom. Toxicon. 2014. doi:10.1016/j.toxicon.2014.02.010.Google Scholar
  25. Cologna CT, Marcussi S, Giglio JR, Soares AM, Arantes EC. Tityus serrulatus scorpion venom and toxins: an overview. Prot Pept Lett. 2009;16(8):920–32.CrossRefGoogle Scholar
  26. Cologna CT, Peigneur S, Rosa JC, Selistre-de-Araujo HS, Varanda WA, Tytgat J, et al. Purification and characterization of Ts15, the first member of a new alpha-KTX subfamily from the venom of the Brazilian scorpion Tityus serrulatus. Toxicon. 2011;58(1):54–61.PubMedCrossRefGoogle Scholar
  27. Cologna CT, Peigneur S, Rustiguel JK, Nonato MC, Tytgat J, Arantes EC. Investigation of the relationship between the structure and function of Ts2, a neurotoxin from Tityus serrulatus venom. Febs J. 2012;279(8):1495–504.PubMedCrossRefGoogle Scholar
  28. Coronas FV, de Roodt AR, Olamendi-Portugal T, Zamudio FZ, Batista CVF, Gomez-Lagunas F, et al. Disulfide bridges and blockage of Shaker B K+-channels by another butantoxin peptide purified from the Argentinean scorpion Tityus trivittatus. Toxicon. 2003;41(2):173–9.PubMedCrossRefGoogle Scholar
  29. De Lima ME, Martin MF, Diniz CR, Rochat H. Tityus serrulatus toxin VII bears pharmacological properties of both β-toxin and insect toxin from scorpion venoms. Biochem Biophys Res Commun. 1986;139(1):296–302.PubMedCrossRefGoogle Scholar
  30. Dodson PD, Barker MC, Forsythe ID. Two heteromeric Kv1 potassium channels differentially regulate action potential firing. J Neurosci. 2002;22(16):6953–61.PubMedGoogle Scholar
  31. Ferreira LAF, Alves EW, Henriques OB. Peptide T, a novel bradykinin potentiator isolated from Tityus serrulatus scorpion venom. Toxicon. 1993;31(8):941–7.PubMedCrossRefGoogle Scholar
  32. Ferreira LAF, Zingalli R, Habermehl G, Lebrun I. Isolation and properties of a new kallikrein inhibitor from Tityus serrulatus venom. J Protein Chem. 1998;17(8):799–805.PubMedCrossRefGoogle Scholar
  33. Fletcher Jr PL, Fletcher MD, Weninger K, Anderson TE, Martin BM. Vesicle-associated membrane protein (VAMP) cleavage by a new metalloprotease from the Brazilian scorpion Tityus serrulatus. J Biol Chem. 2010;285(10):7405–16.PubMedCentralPubMedCrossRefGoogle Scholar
  34. Gordon D, Karbat I, Ilan N, Cohen L, Kahn R, Gilles N, et al. The differential preference of scorpion alpha-toxins for insect or mammalian sodium channels: implications for improved insect control. Toxicon. 2007;49(4):452–72.PubMedCrossRefGoogle Scholar
  35. Guatimosim SC, Prado VF, Diniz CR, Chávez-Olórtegui C, Kalapothakis E. Molecular cloning and genomic analysis of TsNTxp: an immunogenic protein from Tityus serrulatus scorpion venom. Toxicon. 1999;37(3):507–17.PubMedCrossRefGoogle Scholar
  36. Jonas P, Vogel W, Arantes EC, Giglio JR. Toxin gamma of the scorpion Tityus serrulatus modifies both activation and inactivation of sodium permeability of nerve membrane. Pflugers Archiv-Eur J Physiol. 1986;407(1):92–9.CrossRefGoogle Scholar
  37. Kirsch GE, Skattebol A, Possani LD, Brown AM. Modification of Na channel gating by an alpha scorpion toxin from Tityus serrulatus. J Gen Physiol. 1989;93(1):67–83.PubMedCrossRefGoogle Scholar
  38. Legros C, Ceard B, Bougis PE, Martin-Eauclaire MF. Evidence for a new class of scorpion toxins active against K+ channels. Febs Lett. 1998;431(3):375–80.PubMedCrossRefGoogle Scholar
  39. Lutz A, Mello-Campos O. Descripção de 5 espécies brasileiras dos gêneros Tityus e Rhopalurus. Folha Médica. 1922;4:25–26.Google Scholar
  40. Marangoni S, Ghiso J, Sampaio SV, Arantes EC, Giglio JR, Oliveira B, et al. The complete amino acid sequence of toxin TsTX-VI isolated from the venom of the scorpion Tityus serrulatus. J Protein Chem. 1990;9(5):595–601.PubMedCrossRefGoogle Scholar
  41. Marangoni S, Toyama MH, Arantes EC, Giglio J, da Silva CA, Carneiro EM, et al. Amino acid sequence of TsTX-V, an alpha-toxin from Tityus serrulatus scorpion venom, and its effect on K+ permeability of beta-cells from isolated rat islets of Langerhans. Biochim Biophys Acta (BBA)-Gen Subj. 1995;1243(3):309–14.CrossRefGoogle Scholar
  42. Martin-Eauclaire MF, Ceard B, Ribeiro AM, Diniz CR, Rochat H, Bougis PE. Molecular cloning and nucleotide sequence analysis of a cDNA encoding the main beta-neurotoxin from the venom of the South American scorpion Tityus serrulatus. Febs Lett. 1992;302(3):220–2.PubMedCrossRefGoogle Scholar
  43. Martin-Eauclaire M, Céard B, Ribeiro A, Diniz C, Rochat H, Bougis P. Biochemical, pharmacological and genomic characterisation of Ts IV, an α-toxin from the venom of the South American scorpion Tityus serrulatus. FEBS Lett. 1994;342(2):181–4.PubMedCrossRefGoogle Scholar
  44. Matteson DR, Blaustein MP. Scorpion toxin block of the early KC current (I-Kf) in rat dorsal root ganglion neurones. J Physiol-Lond. 1997;503(2):285–301.PubMedCentralPubMedCrossRefGoogle Scholar
  45. Mouhat S, Andreotti N, Jouirou B, Sabatier J-M. Animal toxins acting on voltage-gated potassium channels. Curr Pharm Des. 2008;14(24):2503–18.PubMedCrossRefGoogle Scholar
  46. Neto MDA, Vasconcelos F, Bendhack LM, Arantes EC. Tityus serrulatus venom and its toxins Ts1 and Ts5 increase cytosolic Ca2+ concentration in isolated vascular smooth muscle cells. J Biophys Chem. 2012;3(4):287–94.CrossRefGoogle Scholar
  47. Novello JC, Arantes EC, Varanda WA, Oliveira B, Giglio JR, Marangoni S. TsTX-IV, a short chain four-disulfide-bridged neurotoxin from Tityus serrulatus venom which acts on Ca2+-activated K+ channels. Toxicon. 1999;37(4):651–60.PubMedCrossRefGoogle Scholar
  48. Nunan EA, Cardoso VN, Moraes-Santos T. Lethal effect of the scorpion Tityus serrulatus venom: comparative study on adult and weanling rats. Braz J Pharm Sci. 2001;37(1):39–44.Google Scholar
  49. Nunan EA, Moraes M, Cardoso VN, Moraes-Santos T. Effect of age on body distribution of Tityustoxin from Tityus serrulatus scorpion venom in rats. Life Sci. 2003;73(3):319–25.PubMedCrossRefGoogle Scholar
  50. Oyama S, Pristovsek P, Franzoni L, Pertinhez TA, Schinina E, Lucke C, et al. Probing the pH-dependent structural features of alpha-KTx12.1, a potassium channel blocker from the scorpion Tityus serrulatus. Protein Sci. 2005;14(4):1025–38.PubMedCentralPubMedCrossRefGoogle Scholar
  51. Pessini AC, Takao TT, Cavalheiro EC, Vichnewski W, Sampaio SV, Giglio JR, et al. A hyaluronidase from Tityus serrulatus scorpion venom: isolation, characterization and inhibition by flavonoids. Toxicon. 2001;39(10):1495–504.PubMedCrossRefGoogle Scholar
  52. Pimenta AMC, Stocklin R, Favreau P, Bougis PE, Martin-Eauclaire MF. Moving pieces in a proteomic puzzle: mass fingerprinting of toxic fractions from the venom of Tityus serrulatus (Scorpiones, Buthidae). Rapid Commun Mass Spectrom. 2001;15(17):1562–72.PubMedCrossRefGoogle Scholar
  53. Pimenta AMC, Mansuelle P, Diniz CR, Martin-Eauclaire MF. Covalent structure and some pharmacological features of native and cleaved alpha-KTx12.1, a four disulfide-bridged toxin from Tityus serrulatus venom. J Pept Sci. 2003a;9(2):132–40.PubMedCrossRefGoogle Scholar
  54. Pimenta AMC, Legros C, Almeida FD, Mansuelle P, De Lima ME, Bougis PE, et al. Novel structural class of four disulfide-bridged peptides from Tityus serrulatus venom. Biochem Biophys Res Commun. 2003b;301(4):1086–92.PubMedCrossRefGoogle Scholar
  55. Possani LD, Alagon AC, Fletcher PL, Erickson BW. Purification and properties of mammalian toxins from venom of brazilian scorpion Tityus serrulatus Lutz and Mello. Arch Biochem Biophys. 1977;180(2):394–403.PubMedCrossRefGoogle Scholar
  56. Possani LD, Martin BM, Svendsen IB. The primary structure of noxiustoxin – a K+-channel blocking peptide, purified from the venom of the scorpion Centruroides noxius Hoffmann. Carlsb Res Commun. 1982;47(5):285–9.CrossRefGoogle Scholar
  57. Possani LD, Martin BM, Fletcher MD, Fletcher Jr PL. Discharge effect on pancreatic exocrine secretion produced by toxins purified from Tityus serrulatus scorpion venom. J Biol Chem. 1991;266(5):3178–85.PubMedGoogle Scholar
  58. Possani LD, Becerril B, Delepierre M, Tytgat J. Scorpion toxins specific for Na+-channels. Eur J Biochem. 1999;264(2):287–300.PubMedCrossRefGoogle Scholar
  59. Pucca MB, Roncolato EC, Campos LB, Fernandes FS, Mendes GR, Bertolini TB, et al. Experimental Tityus serrulatus scorpion envenomation: age- and sex-related differences in symptoms and mortality in mice. J Venom Anim Toxins Incl Trop Dis. 2011;17(3):325–32.CrossRefGoogle Scholar
  60. Rates B, Ferraz KKF, Borges MH, Richardson M, De Lima ME, Pimenta AMC. Tityus serrulatus venom peptidomics: assessing venom peptide diversity. Toxicon. 2008;52(5):611–18.PubMedCrossRefGoogle Scholar
  61. Richardson M, Borges MH, Cordeiro MN, Pimenta AMC, de Lima ME, Rates B. Allergenic protein from venom of Brazilian scorpion Tityus serrulatus. 2008a;UniProtKB: P85840.Google Scholar
  62. Richardson M, Borges MH, Cordeiro MN, Pimenta AMC, de Lima ME, Rates B. Hyaluronidase from venom of Brazilian scorpion Tityus serrulatus. 2008b;UniProtKB: P85841.Google Scholar
  63. Richardson M, Borges MH, Cordeiro MN, Pimenta AMC, de Lima ME, Rates B. Metaloproteinase from venom of Brazilian scorpion Tityus serrulatus. 2008c;UniProtKB: P85842.Google Scholar
  64. Rodríguez de la Vega RC, Possani LD. Current views on scorpion toxins specific for K+-channels. Toxicon. 2004;43(8):865–75.PubMedCrossRefGoogle Scholar
  65. Rogers JC, Qu Y, Tanada TN, Scheuer T, Catterall WA. Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3–S4 extracellular loop in domain IV of the Na+ channel alpha subunit. J Biol Chem. 1996;271:15950–62.PubMedCrossRefGoogle Scholar
  66. Rogowski RS, Krueger BK, Collins JH, Blaustein MP. Tityustoxin K alpha blocks voltage-gated noninactivating K+ channels and unblocks inactivating K+ channels blocked by alphadendrotoxin in synaptosomes. Proc Natl Acad Sci U S A. 1994;91(4):1475–9.PubMedCentralPubMedCrossRefGoogle Scholar
  67. Sampaio SV, Laure CJ, Giglio JR. Isolation and characterization of toxic proteins from the venom of the brazilian scorpion Tityus serrulatus. Toxicon. 1983;21(2):265–77.PubMedCrossRefGoogle Scholar
  68. Sampaio SV, CoutinhoNetto J, Arantes EC, Toyama MH, Novello JC, Giglio JR. TsTX-VII, a new toxin from Tityus serrulatus scorpion venom able to induce the release of neurotransmitters from rat brain synaptosomes not blocked by tetrodotoxin. Biochem Mol Biol Int. 1997;41(6):1255–63.PubMedGoogle Scholar
  69. Saucedo AL, Flores-Solis D, de la Vega RCR, Ramirez-Cordero B, Hernandez-Lopez R, Cano-Sanchez P, et al. New tricks of an old pattern – structural versatility of scorpion toxins with common cysteine spacing. J Biol Chem. 2012;287(15):12321–30.PubMedCentralPubMedCrossRefGoogle Scholar
  70. Vasconcelos F, Lanchote VL, Bendhack LM, Giglio JR, Sampaio SV, Arantes EC. Effects of voltage-gated Na+ channel toxins from Tityus serrulatus venom on rat arterial blood pressure and plasma catecholamines. Comp Biochem Physiol C-Toxicol Pharmacol. 2005;141(1):85–92.PubMedCrossRefGoogle Scholar
  71. Venancio EJ, Portaro FC, Kuniyoshi AK, Carvalho DC, Pidde-Queiroz G, Tambourgi DV. Enzymatic properties of venoms from Brazilian scorpions of Tityus genus and the neutralisation potential of therapeutical antivenoms. Toxicon. 2013;69:180–90.PubMedCrossRefGoogle Scholar
  72. Verano-Braga T, Rocha-Resende C, Silva DM, Ianzer D, Martin-Eauclaire MF, Bougis PE, et al. Tityus serrulatus hypotensins: a new family of peptides from scorpion venom. Biochem Biophys Res Commun. 2008;371(3):515–20.PubMedCrossRefGoogle Scholar
  73. Verano-Braga T, Figueiredo-Rezende F, Melo MN, Lautner RQ, Gomes ERM, Mata-Machado LT, et al. Structure-function studies of Tityus serrulatus Hypotensin-I (TsHpt-I): a new agonist of B-2 kinin receptor. Toxicon. 2010;56(7):1162–71.PubMedCrossRefGoogle Scholar
  74. Verano-Braga T, Dutra AA, León IR, Melo-Braga MN, Roepstorff P, Pimenta AM, et al. Moving pieces in a venomic puzzle: unveiling post-translationally modified toxins from Tityus serrulatus. J Proteome Res. 2013;12:3460–70.PubMedCrossRefGoogle Scholar
  75. Zoccal KF, Bitencourt CS, Secatto A, Sorgi CA, Figueredo Bordon KC, Sampaio SV, et al. Tityus serrulatus venom and toxins Ts1, Ts2 and Ts6 induce macrophage activation and production of immune mediators. Toxicon. 2011;57(7–8):1101–8.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Karla de Castro Figueiredo Bordon
    • 1
  • Camila Takeno Cologna
    • 1
    • 2
  • Eliane Candiani Arantes
    • 1
  1. 1.Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão PretoUniversity of São PauloRibeirão PretoBrazil
  2. 2.Laboratoire de Spectrométrie de Masse, CART/GIGA-R, Institut de Chimie, Bat. B6cUniversité de LiègeLiègeBelgium

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