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Peptidome and Transcriptome Analysis of the Toxin-Like Peptides in the Venom Glands of Tarantula Grammostola rosea

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Spider Venoms

Part of the book series: Toxinology ((TOXI))

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Abstract

Tarantula venom glands produce a large variety of bioactive peptides. Chilean common tarantula Grammostola rosea has relatively large venom glands, and the secreted venom and the venom glands have been utilized in both proteomic and genomic approaches, respectively. The expressed sequence tag analysis for the cDNA library has unveiled 48 toxin-like peptides from the tarantula to date. Among them, 24 toxins are inhibitor cystine knot motif peptides (GTx1 and GTx2), 11 peptides (GTx3) are mamba intestinal toxin 1 (MIT1)-like peptides, and 7 are GTx4s similar to ESTX-like peptides identified from another tarantula species. Peptides similar to JZTX-64, aptotoxin, CRISP, or TCTP were also identified. GTx3 series possess a cysteine framework that is conserved among vertebrate MIT1, Bv8, prokineticins, and invertebrate astakines, while these peptides are reported to have diverse bioactivities such as muscle contractions, angiogenesis, etc. GTx-CRISP is the first CRISP-like protein identified from the arthropod vemon. A novel peptide, named GTx1-15, shows 76.5 % sequence homology with phrixotoxin 3(PaurTx3) isolated from another spider. PaurTx3 was characterized to block sodium channels; however, GTx1-15 preferentially inhibited T-type voltage-dependent calcium channels. Secondary and tertiary structure prediction in silico revealed that GTx1-15 and PaurTx3, and other sodium channel blockers such as hainantoxin-IV and ceratotoxin 2 as well, show very similar β-strand composition, distribution of optimal docking areas, and surface electrostatic potential. The findings may suggest that these peptide toxins evolved from common ancestors by gene duplication under evolution pressures to maintain surface environment appropriate for targeting low-voltage-dependent ion channels.

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Abbreviations

EST:

Expressed sequence tag

ICK:

Inhibitor cysteine knot

ODA:

Optimal docking area

RT-PCR:

Reverse transcription polymerase chain reaction

References

  • Bommer UA, Lazaris-Karatzas A, De Benedetti A, Nurnberg P, Benndorf R, Bielka H, Sonenberg N. Translational regulation of the mammalian growth-related protein P23: involvement of eIF-4E. Cell Mol Biol Res. 1994;40:633–41.

    CAS  PubMed  Google Scholar 

  • Bonasio R, Zhang G, Ye C, Mutti NS, Fang X, Qin N, Donahue G, Yang P, Li Q, Li C, Zhang P, Huang Z, Berger SL, Reinberg D, Wang J, Liebig J. Genomic comparison of the ants Camponotus floridanus and Harpegnathos saltator. Science. 2010;329:1068–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bosmans F, Swartz KJ. Targeting voltage sensors in sodium channels with spider toxins. Trends Pharmacol Sci. 2010;31:175–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bosmans F, Rash L, Zhu S, Diochot S, Lazdunski M, Escoubas P, Tytgat J. Four novel tarantula toxins as selective modulators of voltage-gated sodium channel subtypes. Mol Pharmacol. 2006;69:419–29.

    Article  CAS  PubMed  Google Scholar 

  • Bosmans F, Martin-Eauclaire MF, Swartz KJ. Deconstructing voltage sensor function and pharmacology in sodium channels. Nature. 2008;456:202–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Casasoli M, Federici L, Spinelli F, Di Matteo A, Vella N, Scaloni F, Fernandez-Recio J, Cervone F, De Lorenzo G. Integration of evolutionary and desolvation energy analysis identifies functional sites in a plant immunity protein. Proc Natl Acad Sci U S A. 2009;106:7666–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Catterall WA. Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol. 2000;16:521–55.

    Article  CAS  PubMed  Google Scholar 

  • Charest NJ, Joseph DR, Wilson EM, French FS. Molecular cloning of complementary deoxyribonucleic acid for an androgen-regulated epididymal protein: sequence homology with metalloproteins. Mol Endocrinol. 1988;2:999–1004.

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Deng M, He Q, Meng E, Jiang L, Liao Z, Rong M, Liang S. Molecular diversity and evolution of cystine knot toxins of the tarantula Chilobrachys jingzhao. Cell Mol Life Sci. 2008a;65:2431–44.

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Zhao L, Jiang L, Meng E, Zhang Y, Xiong X, Liang S. Transcriptome analysis revealed novel possible venom components and cellular processes of the tarantula Chilobrachys jingzhao venom gland. Toxicon. 2008b;52:794–806.

    Article  CAS  PubMed  Google Scholar 

  • Clement H, Odell G, Zamudio FZ, Redaelli E, Wanke E, Alagon A, Possani LD. Isolation and characterization of a novel toxin from the venom of the spider Grammostola rosea that blocks sodium channels. Toxicon. 2007;50:65–74.

    Article  CAS  PubMed  Google Scholar 

  • Corzo G, Gilles N, Satake H, Villegas E, Dai L, Nakajima T, Haupt J. Distinct primary structures of the major peptide toxins from the venom of the spider Macrothele gigas that bind to sites 3 and 4 in the sodium channel. FEBS Lett. 2003;547:43–50.

    Article  CAS  PubMed  Google Scholar 

  • Corzo G, Bernard C, Clement H, Villegas E, Bosmans F, Tytgat J, Possani LD, Darbon H, Alagon A. Insecticidal peptides from the theraposid spider Brachypelma albiceps: an NMR-based model of Ba2. Biochim Biophys Acta. 2009;1794:1190–6.

    Article  CAS  PubMed  Google Scholar 

  • Craik DJ, Daly NL, Waine C. The cystine knot motif in toxins and implications for drug design. Toxicon. 2001;39:43–60.

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez de la Vega RC. A note on the evolution of spider toxins containing the ICK-motif. Toxin Rev. 2005;24:383–95.

    Google Scholar 

  • Diego-Garcia E, Peigneur S, Waelkens E, Debaveye S, Tytgat J. Venom components from Citharischius crawshayi spider (Family Theraphosidae): exploring transcriptome, venomics, and function. Cell Mol Life Sci CMLS. 2010;67:2799–813.

    Article  CAS  PubMed  Google Scholar 

  • Diochot S, Drici MD, Moinier D, Fink M, Lazdunski M. Effects of phrixotoxins on the Kv4 family of potassium channels and implications for the role of Ito1 in cardiac electrogenesis. Br J Pharmacol. 1999;126:251–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ebbinghaus J, Legros C, Nolting A, Guette C, Celerier ML, Pongs O, Bahring R. Modulation of Kv4.2 channels by a peptide isolated from the venom of the giant bird-eating tarantula Theraphosa leblondi. Toxicon. 2004;43:923–32.

    Article  CAS  PubMed  Google Scholar 

  • Edgerton GB, Blumenthal KM, Hanck DA. Inhibition of the activation pathway of the T-type calcium channel Ca(V)3.1 by ProTxII. Toxicon. 2010;56:624–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Escoubas P, King GF. Venomics as a drug discovery platform. Expert Rev Proteomics. 2009;6:221–4.

    Article  CAS  PubMed  Google Scholar 

  • Escoubas P, Rash L. Tarantulas: eight-legged pharmacists and combinatorial chemists. Toxicon. 2004;43:555–74.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez D, Vendrell J, Aviles FX, Fernandez-Recio J. Structural and functional characterization of binding sites in metallocarboxypeptidases based on optimal docking area analysis. Proteins. 2007;68:131–44.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Recio J, Totrov M, Skorodumov C, Abagyan R. Optimal docking area: a new method for predicting protein-protein interaction sites. Proteins. 2005;58:134–43.

    Article  CAS  PubMed  Google Scholar 

  • Gachet Y, Tournier S, Lee M, Lazaris-Karatzas A, Poulton T, Bommer UA. The growth-related, translationally controlled protein P23 has properties of a tubulin binding protein and associates transiently with microtubules during the cell cycle. J Cell Sci. 1999;112(Pt 8):1257–71.

    CAS  PubMed  Google Scholar 

  • Giannini E, Lattanzi R, Nicotra A, Campese AF, Grazioli P, Screpanti I, Balboni G, Salvadori S, Sacerdote P, Negri L. The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain. Proc Natl Acad Sci U S A. 2009;106:14646–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ibanez-Tallon I, Wen H, Miwa JM, Xing J, Tekinay AB, Ono F, Brehm P, Heintz N. Tethering naturally occurring peptide toxins for cell-autonomous modulation of ion channels and receptors in vivo. Neuron. 2004;43:305–11.

    Article  CAS  PubMed  Google Scholar 

  • Isbister GK, Seymour JE, Gray MR, Raven RJ. Bites by spiders of the family Theraphosidae in humans and canines. Toxicon. 2003;41:519–24.

    Article  CAS  PubMed  Google Scholar 

  • Jiang Y, Lee A, Chen J, Ruta V, Cadene M, Chait BT, MacKinnon R. X-ray structure of a voltage-dependent K+ channel. Nature. 2003;423:33–41.

    Article  CAS  PubMed  Google Scholar 

  • Jiang L, Peng L, Chen J, Zhang Y, Xiong X, Liang S. Molecular diversification based on analysis of expressed sequence tags from the venom glands of the Chinese bird spider Ornithoctonus huwena. Toxicon. 2008;51:1479–89.

    Article  CAS  PubMed  Google Scholar 

  • Kaiser II, Griffin PR, Aird SD, Hudiburg S, Shabanowitz J, Francis B, John TR, Hunt DF, Odell GV. Primary structures of two proteins from the venom of the Mexican red knee tarantula (Brachypelma smithii). Toxicon. 1994;32:1083–93.

    Article  CAS  PubMed  Google Scholar 

  • Kaser A, Winklmayr M, Lepperdinger G, Kreil G. The AVIT protein family. Secreted cysteine-rich vertebrate proteins with diverse functions. EMBO Rep. 2003;4:469–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kierszenbaum AL, Lea O, Petrusz P, French FS, Tres LL. Isolation, culture, and immunocytochemical characterization of epididymal epithelial cells from pubertal and adult rats. Proc Natl Acad Sci U S A. 1981;78:1675–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kimura T, Ono S, Kubo T. Molecular cloning and sequence analysis of the cDNAs encoding toxin-like peptides from the venom glands of tarantula Grammostola rosea. Int J Pept. 2012;2012:731293.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lampe RA, Defeo PA, Davison MD, Young J, Herman JL, Spreen RC, Horn MB, Mangano TJ, Keith RA. Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses. Mol Pharmacol. 1993;44:451–60.

    CAS  PubMed  Google Scholar 

  • Lewis RJ, Garcia ML. Therapeutic potential of venom peptides. Nat Rev Drug Discov. 2003;2:790–802.

    Article  CAS  PubMed  Google Scholar 

  • Li D, Xiao Y, Xu X, Xiong X, Lu S, Liu Z, Zhu Q, Wang M, Gu X, Liang S. Structure–activity relationships of hainantoxin-IV and structure determination of active and inactive sodium channel blockers. J Biol Chem. 2004;279:37734–40.

    Article  CAS  PubMed  Google Scholar 

  • Liang S. An overview of peptide toxins from the venom of the Chinese bird spider Selenocosmia huwena Wang [=Ornithoctonus huwena (Wang)]. Toxicon. 2004;43:575–85.

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Dai J, Chen Z, Hu W, Xiao Y, Liang S. Isolation and characterization of hainantoxin-IV, a novel antagonist of tetrodotoxin-sensitive sodium channels from the Chinese bird spider Selenocosmia hainana. Cell Mol Life Sci. 2003;60:972–8.

    Article  CAS  PubMed  Google Scholar 

  • MacDonald SM, Rafnar T, Langdon J, Lichtenstein LM. Molecular identification of an IgE-dependent histamine-releasing factor. Science. 1995;269:688–90.

    Article  CAS  PubMed  Google Scholar 

  • Mollay C, Wechselberger C, Mignogna G, Negri L, Melchiorri P, Barra D, Kreil G. Bv8, a small protein from frog skin and its homologue from snake venom induce hyperalgesia in rats. Eur J Pharmacol. 1999;374:189–96.

    Article  CAS  PubMed  Google Scholar 

  • Narasimhan L, Singh J, Humblet C, Guruprasad K, Blundell T. Snail and spider toxins share a similar tertiary structure and “cystine motif”. Nat Struct Biol. 1994;1:850–2.

    Article  CAS  PubMed  Google Scholar 

  • Negri L, Lattanzi R, Giannini E, Melchiorri P. Bv8/Prokineticin proteins and their receptors. Life Sci. 2007;81:1103–16.

    Article  CAS  PubMed  Google Scholar 

  • Negri L, Lattanzi R, Giannini E, Canestrelli M, Nicotra A, Melchiorri P. Bv8/Prokineticins and their receptors a new pronociceptive system. Int Rev Neurobiol. 2009;85:145–57.

    Article  CAS  PubMed  Google Scholar 

  • Nobile M, Noceti F, Prestipino G, Possani LD. Helothermine, a lizard venom toxin, inhibits calcium current in cerebellar granules. Exp Brain Res Experimentelle Hirnforschung Experimentation cerebrale. 1996;110:15–20.

    Article  CAS  PubMed  Google Scholar 

  • Ono S, Kimura T, Kubo T. Characterization of voltage-dependent calcium channel blocking peptides from the venom of the tarantula Grammostola rosea. Toxicon. 2011;58:265–76.

    Article  CAS  PubMed  Google Scholar 

  • Ostrow KL, Mammoser A, Suchyna T, Sachs F, Oswald R, Kubo S, Chino N, Gottlieb PA. cDNA sequence and in vitro folding of GsMTx4, a specific peptide inhibitor of mechanosensitive channels. Toxicon. 2003;42:263–74.

    Article  CAS  PubMed  Google Scholar 

  • Oswald RE, Suchyna TM, McFeeters R, Gottlieb P, Sachs F. Solution structure of peptide toxins that block mechanosensitive ion channels. J Biol Chem. 2002;277:34443–50.

    Article  CAS  PubMed  Google Scholar 

  • Pallaghy PK, Nielsen KJ, Craik DJ, Norton RS. A common structural motif incorporating a cystine knot and a triple-stranded beta-sheet in toxic and inhibitory polypeptides. Protein Sci. 1994;3:1833–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perez-Reyes E. Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev. 2003;83:117–61.

    Article  CAS  PubMed  Google Scholar 

  • Perret D, Luo ZD. Targeting voltage-gated calcium channels for neuropathic pain management. Neurotherapeutics. 2009;6:679–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Redaelli E, Cassulini RR, Silva DF, Clement H, Schiavon E, Zamudio FZ, Odell G, Arcangeli A, Clare JJ, Alagon A, de la Vega RC, Possani LD, Wanke E. Target promiscuity and heterogeneous effects of tarantula venom peptides affecting N+ and K+ ion channels. J Biol Chem. 2010;285:4130–42.

    Article  CAS  PubMed  Google Scholar 

  • Savel-Niemann A. Tarantula (Eurypelma californicum) venom, a multicomponent system. Biol Chem Hoppe Seyler. 1989;370:485–98.

    Article  CAS  PubMed  Google Scholar 

  • Schmalhofer WA, Calhoun J, Burrows R, Bailey T, Kohler MG, Weinglass AB, Kaczorowski GJ, Garcia ML, Koltzenburg M, Priest BT. ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors. Mol Pharmacol. 2008;74:1476–84.

    Article  CAS  PubMed  Google Scholar 

  • Schweitz H, Pacaud P, Diochot S, Moinier D, Lazdunski M. MIT(1), a black mamba toxin with a new and highly potent activity on intestinal contraction. FEBS Lett. 1999;461:183–8.

    Article  CAS  PubMed  Google Scholar 

  • Skinner WS, Dennis PA, Li JP, Quistad GB. Identification of insecticidal peptides from venom of the trap-door spider, Aptostichus schlingeri (Ctenizidae). Toxicon. 1992;30:1043–50.

    Article  CAS  PubMed  Google Scholar 

  • Smith JJ, Cummins TR, Alphy S, Blumenthal KM. Molecular interactions of the gating modifier toxin ProTx-II with Nav1.5: Inplied existence of a novel toxin bindhing site coupled to activation. J Biol Chem. 2007;282:12687–97.

    Article  CAS  PubMed  Google Scholar 

  • Soderhall I, Kim YA, Jiravanichpaisal P, Lee SY, Soderhall K. An ancient role for a prokineticin domain in invertebrate hematopoiesis. J Immunol. 2005;174:6153–60.

    Article  PubMed  Google Scholar 

  • Swartz KJ, MacKinnon R. An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula. Neuron. 1995;15:941–9.

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi K, Park E, Lee C, Kim J, Takahashi H, Swartz K, Shimada I. Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and N-type Ca(2+) channel. J Mol Biol. 2002;321:517–26.

    Article  CAS  PubMed  Google Scholar 

  • Tang X, Zhang Y, Liang S. Large-scale identification and analysis of peptide toxins from the tarantula Ornithoctonus hainana venom using a venomic strategy. NCBI, Direct Submission. Accession No. GU293118; 2010.

    Google Scholar 

  • Torres AM, Wong HY, Desai M, Moochhala S, Kuchel PW, Kini RM. Identification of a novel family of proteins in snake venoms. Purification and structural characterization of nawaprin from Naja nigricollis snake venom. J Biol Chem. 2003;278:40097–104.

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Cao G, Pavlicek B, Luo X, Nitabach MN. Phase coupling of a circadian neuropeptide with rest/activity rhythms detected using a membrane-tethered spider toxin. PLoS Biol. 2008;6, e273.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yamazaki Y, Koike H, Sugiyama Y, Motoyoshi K, Wada T, Hishinuma S, Mita M, Morita T. Cloning and characterization of novel snake venom proteins that block smooth muscle contraction. Eur J Biochem. 2002;269:2708–15.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y. Transcriptome analysis of Lycosa singoriensis spider venomous gland. NCBI, Direct Submission. Accession No. FM864147; 2008.

    Google Scholar 

  • Zhang B, Liu Q, Yin W, Zhang X, Huang Y, Luo Y, Qiu P, Su X, Yu J, Hu S, Yan G. Transcriptome analysis of Deinagkistrodon acutus venomous gland focusing on cellular structure and functional aspects using expressed sequence tags. BMC Genomics. 2006;7:152.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Molecular Neurophysiology Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan

    Tadashi Kimura & Tai Kubo

  2. Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Koto-ku, Tokyo, 135-0064, Japan

    Tai Kubo

  3. United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Tadashi Kimura & Tai Kubo

  4. Division of Biotechnology, The Institution of Professional Engineers, Japan (IPEJ), Tokyo, Japan

    Tadashi Kimura

  5. Laboratory for Drug Discovery, and Glycoscience and Glycotechnology Research Group, Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan

    Tadashi Kimura

Authors
  1. Tadashi Kimura
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  2. Tai Kubo
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Correspondence to Tadashi Kimura .

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Editors and Affiliations

  1. Department of Anatomy, Yong Loo Lin School of Medicine National University of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Department of Molecular Medicine and Bioprocesses, The Biotechnology Institute National Autonomous University of Mexico (UNAM), Cuernavaca, Morelos, Mexico

    Gerardo A. Corzo

  3. Departamento de Bioquímica e Imunologia Laboratório de Venenos e Toxinas Animais, Instituto de Ciências Biológicas Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Maria Elena de Lima

  4. Veerle, Belgium

    Elia Diego-García

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Kimura, T., Kubo, T. (2016). Peptidome and Transcriptome Analysis of the Toxin-Like Peptides in the Venom Glands of Tarantula Grammostola rosea . In: Gopalakrishnakone, P., Corzo, G., de Lima, M., Diego-García, E. (eds) Spider Venoms. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6389-0_13

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