sevinПОВОЛЖСКИЙ ЭКОЛОГИЧЕСКИЙ ЖУРНАЛPovolzhskiy Journal of Ecology1684-73182541-8963Федеральное государственное бюджетное учреждение науки Институт проблем экологии и эволюции им. А. Н. Северцова РАН; Товарищество научных изданий КМК.10.35885/1684-7318-2024-4-410-430sevin-602Research ArticleСтатьиТоксины яда пауков-птицеедов (Theraphosidae, Arachnida) в межвидовых взаимодействияхToxins of the venom of tarantulas (Theraphosidae, Arachnida) in interspecies interactionshttps://orcid.org/0009-0008-3664-8112ГелашвилиД. Б.GelashviliDavid B.

Гелашвили Давид Бежанович, Институт биологии и биомедицины

603950, г. Нижний Новгород, просп. Гагарина, д. 23

23 Gagarin Avenue, Nizhni Novgorod 603950

gelashvili.david@gmail.comhttps://orcid.org/0000-0002-1925-7864РомановаЕ. Б.RomanovaElena B.

Романова Елена Борисовна

603950, г. Нижний Новгород, просп. Гагарина, д. 23

23 Gagarin Avenue, Nizhni Novgorod 603950

romanova@ibbm.unn.ruНациональный исследовательский Нижегородский государственный университет им. Н. И. ЛобачевскогоРоссияLobachevsky State University of Nizhni NovgorodRussian Federation20242312202404410 – 430Copyright © Гелашвили Д.Б., Романова Е.Б., 20242024Гелашвили Д.Б., Романова Е.Б.Gelashvili D.B., Romanova E.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://sevin.elpub.ru/jour/article/view/602

Пауки, как важнейшие энтомофаги экосистем, являются самыми многочисленными ядовитыми животными на планете и незаменимыми регуляторами численности популяций, истребляя, главным образом, насекомых и других мелких членистоногих. Пауки – неотъемлемая часть трофической цепи, они производят яд, который служит для обездвиживания добычи. Яды пауков являются «природной комбинаторной библиотекой» биологически активных веществ, с различной эффективностью и специфичностью. Особенностью биологического действия яда пауков является уникальное сочетание относительно низкой общей токсичности цельного яда, как для животных, так и для человека, с высокой селективностью взаимодействия нейротоксинов, входящих в состав яда, с молекулярными структурами ионных каналов и синаптических рецепторов нервной системы. Обзор знакомит с новыми фундаментальными фактами и идеями в активно развивающейся области изучения яда пауков-птицеедов и перспектив их практического применения в биомедицинских исследованиях для рационального конструирования лекарств (drug design). Рассмотрено современное состояние исследований уникального набора полипептидных токсинов, служащих химическими факторами (алломонами) межвидовых (аллелохимических) взаимодействий пауков-птицеедов семейства Thetaphosidae. Современная информация о структуре токсинов яда пауков-птицеедов анализируется по базе данных UniProt. Приведена новейшая биоэкологическая и токсинологическая характеристика пауков-птицеедов. Рассмотрена химическая природа и механизм действия уникальных токсинов, селективно действующих на ключевые процессы в нервной системе: синаптическую передачу и функционирование ионных каналов, что позволяет паукам-птицеедам не только взаимодействовать с различными молекулярными мишенями жертвы или хищника, но и реализовывать различные жизненные стратегии, приобретая эволюционное преимущество. 

Spiders are the most important entomophages in ecosystems. They are the most numerous poisonous animals on the planet, indispensable regulators of populations’ numbers by killing mainly insects and other small arthropods. Spiders are an integral part of the food chain; they produce venom serving to immobilize the prey. Spider venoms are a “natural combinatorial library” of biologically active substances, with varying effectiveness and specificity. A feature of the biological effect of spider’s venom is a unique combination of the low toxicity of the whole venom, for both animals and humans, with high selectivity of the interaction of the neurotoxins, which are part of the venom, with the molecular structures of ion channels and synaptic receptors of the nervous system. The present review introduces the reader to new fundamental facts, ideas and perspective of the practical application of spider’s venoms in biomedical research and drug design. The current state of research on a unique set of polypeptide toxins which serve as chemical factors (allomons) of the interspecific (allelochemical) interactions of spiders of the family Thetaphosidae is considered. Modern information on the structure of spiders’ venom toxins is analyzed using the UniProt database. The latest bioecological and toxicological characteristics of tarantulas are presented. The chemical nature and mechanism of action of some unique toxins selectively acting on key processes in the nervous system are considered. The toxins act upon synaptic transmission and the functioning ion channels, which allow spiders not only to interact with various molecular targets of the prey or predator, but also to implement various life strategies, gaining an evolutionary advantage. 

пауки-птицеедыTheraphosidaeалломоныполипептидные токсиныspidersTheraphosidaeallomonspolypeptide toxinsReferencesAgwa A. J., Lawrence N., Deplazes E., Cheneval O., Chen R. M., Craik D. J., Schroeder C. I., Henriques S.T. Spider peptide toxin HwTx-IV engineered to bind to lipid membranes has an increased inhibitory potency at human voltage-gated sodium channel hNav1.7. Biochimica et Biophysica Acta, 2017, vol. 1859, no. 5, pp. 835–844. https://doi.org/10.1016/j.bbamem.2017.01.020Agwa A. J., Lawrence N., Deplazes E., Cheneval O., Chen R. M., Craik D. J., Schroeder C. I., Henriques S.T. Spider peptide toxin HwTx-IV engineered to bind to lipid membranes has an increased inhibitory potency at human voltage-gated sodium channel hNav1.7. Biochimica et Biophysica Acta, 2017, vol. 1859, no. 5, pp. 835–844. https://doi.org/10.1016/j.bbamem.2017.01.020Ardisson-Araújo D. M. P., Morgado F. D. S., Schwartz E. F., Corzo G., Ribeiro B. M. A new theraphosid spider toxin causes early insect cell death by necrosis when expressed in vitro during recombinant baculovirus infection. PLoS ONE, 2013, vol. 12, no. 8, article no. e84404. https://doi.org/10.1371/journal.pone.0084404Ardisson-Araújo D. M. P., Morgado F. D. S., Schwartz E. F., Corzo G., Ribeiro B. M. A new theraphosid spider toxin causes early insect cell death by necrosis when expressed in vitro during recombinant baculovirus infection. PLoS ONE, 2013, vol. 12, no. 8, article no. e84404. https://doi.org/10.1371/journal.pone.0084404Bowman C. L., Gottlieb P. A., Suchyna T. M., Murphy Y. K., Sachs F. Mechanosensitive ion channels and the peptide inhibitor GsMTx-4: History, properties, mechanisms and pharmacology. Toxicon, 2007, vol. 49, iss. 2, pp. 249–270. https://doi.org/10.1016/j.toxicon.2006.09.030Bowman C. L., Gottlieb P. A., Suchyna T. M., Murphy Y. K., Sachs F. Mechanosensitive ion channels and the peptide inhibitor GsMTx-4: History, properties, mechanisms and pharmacology. Toxicon, 2007, vol. 49, iss. 2, pp. 249–270. https://doi.org/10.1016/j.toxicon.2006.09.030Chan T. K., Geren C. R., Howell D. E., Odell G. V. Adenosine triphosphate in tarantula spider venoms and its synergistic effect with the venom toxin. Toxicon, 1975, vol. 13, iss. 1, pp. 61–66.Chan T. K., Geren C. R., Howell D. E., Odell G. V. Adenosine triphosphate in tarantula spider venoms and its synergistic effect with the venom toxin. Toxicon, 1975, vol. 13, iss. 1, pp. 61–66.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. Cellular and Molecular Life Sciences, 2008, vol. 65, iss. 15, pp. 2431–2444. https://doi.org/10.1007/s00018-008-8135-xChen 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. Cellular and Molecular Life Sciences, 2008, vol. 65, iss. 15, pp. 2431–2444. https://doi.org/10.1007/s00018-008-8135-xCheng T.-C., Long R.-W., Wu Y.-Q., Guo Y.-B., Liu D.-L., Peng L., Li D.-Q., Yang D.-W., Xu X., Liu F.-X., Хia Q.-Y. Identification and characterization of toxins in the venom gland of the Chinese bird spider, Haplopelma hainanum, by transcriptomic analysis. Insect Science, 2016, vol. 23, iss. 3, pp. 487–499. https://doi.org/10.1111/1744-7917.12305Cheng T.-C., Long R.-W., Wu Y.-Q., Guo Y.-B., Liu D.-L., Peng L., Li D.-Q., Yang D.-W., Xu X., Liu F.-X., Хia Q.-Y. Identification and characterization of toxins in the venom gland of the Chinese bird spider, Haplopelma hainanum, by transcriptomic analysis. Insect Science, 2016, vol. 23, iss. 3, pp. 487–499. https://doi.org/10.1111/1744-7917.12305Cromer B. A., McIntyre P. Painful toxins acting at TRPV1. Toxicon, 2008, vol. 51, iss. 2, pp. 163–173.Cromer B. A., McIntyre P. Painful toxins acting at TRPV1. Toxicon, 2008, vol. 51, iss. 2, pp. 163–173.Dawson R. J., Benz J., Stohler P., Tetaz T., Joseph C., Huber S., Schmid G., Hügin D., Pflimlin P., Trube G., Rudolph M.G., Hennig M., Ruf A. Structure of the acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1. Nature Communications, 2012, no. 3, article no. 936. https://doi.org/10.1038/ncomms1917Dawson R. J., Benz J., Stohler P., Tetaz T., Joseph C., Huber S., Schmid G., Hügin D., Pflimlin P., Trube G., Rudolph M.G., Hennig M., Ruf A. Structure of the acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1. Nature Communications, 2012, no. 3, article no. 936. https://doi.org/10.1038/ncomms1917Deng M., Luo X., Xiao Y., Sun Z., Jiang L., Liu Z., Zeng X., Chen H., Tang J., Zeng W., Liang S. Huwentoxin-XVI, an analgesic, highly reversible mammalian N-type calcium channel antagonist from Chinese tarantula Ornithoctonus huwena. Neuropharmacology, 2014, vol. 79, pp. 657–667. https://doi.org/10.1016/j.neuropharm.2014.01.017Deng M., Luo X., Xiao Y., Sun Z., Jiang L., Liu Z., Zeng X., Chen H., Tang J., Zeng W., Liang S. Huwentoxin-XVI, an analgesic, highly reversible mammalian N-type calcium channel antagonist from Chinese tarantula Ornithoctonus huwena. Neuropharmacology, 2014, vol. 79, pp. 657–667. https://doi.org/10.1016/j.neuropharm.2014.01.017Escoubas P., Bernard C., Lambeau G., Lazdunski M., Darbon H. Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels. Protein Science, 2003, vol. 12, iss. 7, pp. 1332–1343. https://doi.org/10.1110/ps.0307003Escoubas P., Bernard C., Lambeau G., Lazdunski M., Darbon H. Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels. Protein Science, 2003, vol. 12, iss. 7, pp. 1332–1343. https://doi.org/10.1110/ps.0307003Escoubas P., De Weille J. R., Lecoq A., Diochot S., Waldmann R., Champigny G., Moinier D., Ménez A., Lazdunski M. Isolation of a tarantula toxin specific for a class of proton-gated Na+channels. Journal of Biological Chemistry, 2000, vol. 275, iss. 33, pp. 25116–25121. https://doi.org/10.1074/jbc.M003643200Escoubas P., De Weille J. R., Lecoq A., Diochot S., Waldmann R., Champigny G., Moinier D., Ménez A., Lazdunski M. Isolation of a tarantula toxin specific for a class of proton-gated Na+channels. Journal of Biological Chemistry, 2000, vol. 275, iss. 33, pp. 25116–25121. https://doi.org/10.1074/jbc.M003643200Escoubas P., Diochot S., Celerier M.-L., Nakajima T., Lazdunski M. Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies. Molecular Pharmacology, 2002, vol. 62, iss. 1, pp. 48–57. https://doi.org/10.1124/mol.62.1.48Escoubas P., Diochot S., Celerier M.-L., Nakajima T., Lazdunski M. Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies. Molecular Pharmacology, 2002, vol. 62, iss. 1, pp. 48–57. https://doi.org/10.1124/mol.62.1.48Escoubas P., Rash L. Tarantulas: Eight-legged pharmacists and combinatorial chemists. Toxicon, 2004, vol. 43, iss. 5, pp. 555–574. https://doi.org/10.1016/j.toxicon.2004.02.007Escoubas P., Rash L. Tarantulas: Eight-legged pharmacists and combinatorial chemists. Toxicon, 2004, vol. 43, iss. 5, pp. 555–574. https://doi.org/10.1016/j.toxicon.2004.02.007Fletcher J. I., Wang X., Connor M., Christie M. J., King G. F., Nicholson G. M. Spider toxins: A new group of potassium channel modulators. Perspectives in Drug Discovery and Design, 1999, vol. 15, iss. 1, pp. 61–69.Fletcher J. I., Wang X., Connor M., Christie M. J., King G. F., Nicholson G. M. Spider toxins: A new group of potassium channel modulators. Perspectives in Drug Discovery and Design, 1999, vol. 15, iss. 1, pp. 61–69.Gelashvili D. B., Krylov V. N., Romanova E. B. Zootoxinology: Bioecological and Biomedical Aspects. Nizhnij Novgorod, Lobachevsky State University of Nizhni Novgorod Publ., 2015. 770 p. (in Russian).Gelashvili D. B., Krylov V. N., Romanova E. B. Zootoxinology: Bioecological and Biomedical Aspects. Nizhnij Novgorod, Lobachevsky State University of Nizhni Novgorod Publ., 2015. 770 p. (in Russian).Gladkikh I. N., Sintsova O. V., Leychenko E. V., Kozlov S. A. TRPV1 ion channel: Structural features, activity modulators, and therapeutic potential. Biochemistry, 2021, vol. 86, supll. 1, pp. 50–70. https://doi.org/10.1134/S0006297921140054Gladkikh I. N., Sintsova O. V., Leychenko E. V., Kozlov S. A. TRPV1 ion channel: Structural features, activity modulators, and therapeutic potential. Biochemistry, 2021, vol. 86, supll. 1, pp. 50–70. https://doi.org/10.1134/S0006297921140054Herrington J. Gating modifier peptides as probes of pancreatic β-cell physiology. Toxicon, 2007, vol. 49, iss. 2, pp. 231–238. https://doi.org/10.1016/j.toxicon.2006.09.012Herrington J. Gating modifier peptides as probes of pancreatic β-cell physiology. Toxicon, 2007, vol. 49, iss. 2, pp. 231–238. https://doi.org/10.1016/j.toxicon.2006.09.012Herzig V. Arthropod assassins: Crawling biochemists with diverse toxin pharmacopeias. Toxicon, 2019, vol. 158, pp. 33–37. https://doi.org/10.1016/j.toxicon.2018.11.312Herzig V. Arthropod assassins: Crawling biochemists with diverse toxin pharmacopeias. Toxicon, 2019, vol. 158, pp. 33–37. https://doi.org/10.1016/j.toxicon.2018.11.312Hesselberg T., Galvez D. Spider ecology and behaviour–spiders as model organisms. Insects, 2023, vol. 14, no. 4, article no. 330. https://doi.org/10.3390/insects14040330Hesselberg T., Galvez D. Spider ecology and behaviour–spiders as model organisms. Insects, 2023, vol. 14, no. 4, article no. 330. https://doi.org/10.3390/insects14040330Khan S. A., Zafar Y., Briddon R. W., Malik K. A., Mukhtar Z. Spider venom toxin protects plants from insect attack. Transgenic Research, 2006, vol. 15, iss. 3, pp. 349–357. https://doi.org/10.1007/s11248-006-0007-2Khan S. A., Zafar Y., Briddon R. W., Malik K. A., Mukhtar Z. Spider venom toxin protects plants from insect attack. Transgenic Research, 2006, vol. 15, iss. 3, pp. 349–357. https://doi.org/10.1007/s11248-006-0007-2King G. F., Gentz M. C., Escoubas P., Graham M. N. A rational nomenclature for naming peptide toxins from spiders and other venomous animals. Toxicon, 2008, vol. 52, iss. 2, pp. 264–276. https://doi.org/10.1016/j.toxicon.2008.05.020King G. F., Gentz M. C., Escoubas P., Graham M. N. A rational nomenclature for naming peptide toxins from spiders and other venomous animals. Toxicon, 2008, vol. 52, iss. 2, pp. 264–276. https://doi.org/10.1016/j.toxicon.2008.05.020Kuhn-Nentwig L., Stocklin R., Nentwig W. Venom composition and strategies in spiders: Is everything possible? Advances in Insect Physiology, 2011, vol. 40, pp. 1–86. https://doi.org/10.1016/B978-0-12-387668-3.00001-5Kuhn-Nentwig L., Stocklin R., Nentwig W. Venom composition and strategies in spiders: Is everything possible? Advances in Insect Physiology, 2011, vol. 40, pp. 1–86. https://doi.org/10.1016/B978-0-12-387668-3.00001-5Lampe R. A., Defeo P. A., Davison M. D., Young J., Herman J. L., Spreen R. C., Horn M. B., Mangano T. J., Keith R. A. Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses. Molecular Pharmacology, 1993, vol. 44, iss. 2, pp. 451–460.Lampe R. A., Defeo P. A., Davison M. D., Young J., Herman J. L., Spreen R. C., Horn M. B., Mangano T. J., Keith R. A. Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses. Molecular Pharmacology, 1993, vol. 44, iss. 2, pp. 451–460.Lee S., Milescu M., Jung H. H., Lee J. Y., Bae C. H., Lee C. W., Kim H. H., Swartz K. J., Kim J. I. Solution structure of GxTX-1E, a high-affinity tarantula toxin interacting with voltage sensors in Kv2.1 potassium channels. Biochemistry, 2010, vol. 49, iss. 25, pp. 5134–5142. https://doi.org/10.1021/bi100246uLee S., Milescu M., Jung H. H., Lee J. Y., Bae C. H., Lee C. W., Kim H. H., Swartz K. J., Kim J. I. Solution structure of GxTX-1E, a high-affinity tarantula toxin interacting with voltage sensors in Kv2.1 potassium channels. Biochemistry, 2010, vol. 49, iss. 25, pp. 5134–5142. https://doi.org/10.1021/bi100246uLi D., Xiao Y., Hu W., Xie J., Bosmans F., Tytgat J., Liang S. Function and solution structure of hainantoxin-I, a novel insect sodium channel inhibitor from the Chinese bird spider Selenocosmia hainana. FEBS Letters, 2003, vol. 555, iss.3, pp. 616–622. https://doi.org/10.1016/s00145793(03)01303-6Li D., Xiao Y., Hu W., Xie J., Bosmans F., Tytgat J., Liang S. Function and solution structure of hainantoxin-I, a novel insect sodium channel inhibitor from the Chinese bird spider Selenocosmia hainana. FEBS Letters, 2003, vol. 555, iss.3, pp. 616–622. https://doi.org/10.1016/s00145793(03)01303-6Liang S. An overview of peptide toxins from the venom of the Chinese bird spider Selenocosmia huwena Wang [=Ornithoctonus huwena (Wang)]. Toxicon, 2004, vol. 43, iss. 5, pp. 575–585. https://doi.org/10.1016/j.toxicon.2004.02.005Liang S. An overview of peptide toxins from the venom of the Chinese bird spider Selenocosmia huwena Wang [=Ornithoctonus huwena (Wang)]. Toxicon, 2004, vol. 43, iss. 5, pp. 575–585. https://doi.org/10.1016/j.toxicon.2004.02.005Liao Z., Cao J., Li S., Yan X., Hu W., He Q., Chen J., Tang J., Xie J., Liang S. Proteomic and peptidomic analysis of the venom from Chinese tarantula Chilobrachys jingzhao. Proteomics, 2007, vol. 7, iss. 11, pp. 1892–1907. https://doi.org/10.1002/pmic.200600785Liao Z., Cao J., Li S., Yan X., Hu W., He Q., Chen J., Tang J., Xie J., Liang S. Proteomic and peptidomic analysis of the venom from Chinese tarantula Chilobrachys jingzhao. Proteomics, 2007, vol. 7, iss. 11, pp. 1892–1907. https://doi.org/10.1002/pmic.200600785Liu Z., Cai T., Zhu Q., Deng M., Li J., Zhou X., Zhang F., Li D., Liu Y., Hu W., Liang S. Structure and function of hainantoxin-III, a selective antagonist of neuronal tetrodotoxin-sensitive voltage-gated sodium channels isolated from the chinese bird spider Ornithoctonus hainana. Journal of Biological Chemistry, 2013, vol. 288, iss. 28, pp. 20392–20403. https://doi.org/10.1074/jbc.m112.426627Liu Z., Cai T., Zhu Q., Deng M., Li J., Zhou X., Zhang F., Li D., Liu Y., Hu W., Liang S. Structure and function of hainantoxin-III, a selective antagonist of neuronal tetrodotoxin-sensitive voltage-gated sodium channels isolated from the chinese bird spider Ornithoctonus hainana. Journal of Biological Chemistry, 2013, vol. 288, iss. 28, pp. 20392–20403. https://doi.org/10.1074/jbc.m112.426627Lüddecke T., Herzig V., von Reumont B. M., Vilcinskas A. The biology and evolution of spider venoms. Biological Reviews, 2022, vol. 97, pp. 163–178. https://doi.org/10.1111/brv.12793Lüddecke T., Herzig V., von Reumont B. M., Vilcinskas A. The biology and evolution of spider venoms. Biological Reviews, 2022, vol. 97, pp. 163–178. https://doi.org/10.1111/brv.12793Middleton R. E., Warren V. A., Kraus R. L., Hwang J. C., Liu C. J., Dai G., Brochu R. M., Kohler M. G., Gao Y.-D., Garsky V. M., Bogusky M. J., Mehl J. T., Cohen C. J., Smith M. M. Two tarantula peptides inhibit activation of multiple sodium channels. Biochemistry, 2002, vol. 41, iss. 50, pp. 14734–14747. https://doi.org/10.1021/bi026546aMiddleton R. E., Warren V. A., Kraus R. L., Hwang J. C., Liu C. J., Dai G., Brochu R. M., Kohler M. G., Gao Y.-D., Garsky V. M., Bogusky M. J., Mehl J. T., Cohen C. J., Smith M. M. Two tarantula peptides inhibit activation of multiple sodium channels. Biochemistry, 2002, vol. 41, iss. 50, pp. 14734–14747. https://doi.org/10.1021/bi026546aOdell G. V., Ownby C. L., Christian C. D., Hudiburg S. A., Herrero V., Swartz P. D., Hooper K. P. A review of research on tarantula colony maintenance, venom collection, composition and toxicity. Toxicon, 1987, vol. 25, iss. 2, pp. 151. https://doi.org/10.1016/0041-0101(87)90219-4 Osteen J. D., Herzig V., Gilchrist J., Emrick J. J., Zhang C., Wang X., Castro J., GarciaCaraballo S., Grundy L., Rychkov G. Y. Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. Nature, 2016, vol. 534, no. 7680, pp. 494–499. https://doi.org/10.1038/nature17976Odell G. V., Ownby C. L., Christian C. D., Hudiburg S. A., Herrero V., Swartz P. D., Hooper K. P. A review of research on tarantula colony maintenance, venom collection, composition and toxicity. Toxicon, 1987, vol. 25, iss. 2, pp. 151. https://doi.org/10.1016/0041-0101(87)90219-4 Osteen J. D., Herzig V., Gilchrist J., Emrick J. J., Zhang C., Wang X., Castro J., GarciaCaraballo S., Grundy L., Rychkov G. Y. Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. Nature, 2016, vol. 534, no. 7680, pp. 494–499. https://doi.org/10.1038/nature17976Ostrow K. L., Mammoser A., Suchyna T., Sachs F., Oswald R., Kubo S., Chino N., Gottlieb P. A. cDNA sequence and in vitro folding of GsMTx4, a specific peptide inhibitor of mechanosensitive channels. Toxicon, 2003, vol. 42, iss. 3, pp. 263–274. https://doi.org/10.1016/s00410101(03)00141-7Ostrow K. L., Mammoser A., Suchyna T., Sachs F., Oswald R., Kubo S., Chino N., Gottlieb P. A. cDNA sequence and in vitro folding of GsMTx4, a specific peptide inhibitor of mechanosensitive channels. Toxicon, 2003, vol. 42, iss. 3, pp. 263–274. https://doi.org/10.1016/s00410101(03)00141-7Pekar S., Coddington J. A., Blackledge T. A. Evolution of stenophagy in spiders (Araneae): Evidence based on the comparative analysis of spider diets. Evolution, 2011, vol. 66, iss. 3, pp. 776–778. https://doi.org/10.1111/j.1558-5646.2011.01471.xPekar S., Coddington J. A., Blackledge T. A. Evolution of stenophagy in spiders (Araneae): Evidence based on the comparative analysis of spider diets. Evolution, 2011, vol. 66, iss. 3, pp. 776–778. https://doi.org/10.1111/j.1558-5646.2011.01471.xPérez-Miles F. Introduction to the Theraphosidae. In: Pérez-Miles F., ed. New World Tarantulas: Taxonomy, Biogeography and Evolutionary Biology of Theraphosidae. Cham, Springer Nature, 2020, pp. 1–24. https://doi.org/10.1007/978-3-030-48644-0_1Pérez-Miles F. Introduction to the Theraphosidae. In: Pérez-Miles F., ed. New World Tarantulas: Taxonomy, Biogeography and Evolutionary Biology of Theraphosidae. Cham, Springer Nature, 2020, pp. 1–24. https://doi.org/10.1007/978-3-030-48644-0_1Pineda S. S., Chin Y. K. Y., Undheim E. A. B., King G. F. Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene. Proceedings of the National Academy of Sciences, 2020, vol. 117, no. 21, pp. 11399–11408. https://doi.org/10.1073/pnas.1914536117Pineda S. S., Chin Y. K. Y., Undheim E. A. B., King G. F. Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene. Proceedings of the National Academy of Sciences, 2020, vol. 117, no. 21, pp. 11399–11408. https://doi.org/10.1073/pnas.1914536117Piser T. M., Lampe R. A., Keith R. A., Thayer S. A. Complete and reversible block by ωgrammotoxin SIA of glutamatergic synaptic transmission between cultured rat hippocampal neurons. Neuroscience Letters, 1995, vol. 201, iss. 2, pp. 135–138. https://doi.org/10.1016/03043940(95)12169-2Piser T. M., Lampe R. A., Keith R. A., Thayer S. A. Complete and reversible block by ωgrammotoxin SIA of glutamatergic synaptic transmission between cultured rat hippocampal neurons. Neuroscience Letters, 1995, vol. 201, iss. 2, pp. 135–138. https://doi.org/10.1016/03043940(95)12169-2Platnick N. I., ed. Spiders of the World: A Natural History. Princeton, Princeton University Press, 2020. 257 p. https://doi.org/10.1525/9780691204987Platnick N. I., ed. Spiders of the World: A Natural History. Princeton, Princeton University Press, 2020. 257 p. https://doi.org/10.1525/9780691204987Priest B. T., Blumenthal K. M., Smith J. J., Warren V. A., Smith M. M. ProTx-I and ProTxII: Gating modifiers of voltage-gated sodium channels. Toxicon, 2007, vol. 49, iss. 2, pp. 194–201. https://doi.org/10.1016/j.toxicon.2006.09.014Priest B. T., Blumenthal K. M., Smith J. J., Warren V. A., Smith M. M. ProTx-I and ProTxII: Gating modifiers of voltage-gated sodium channels. Toxicon, 2007, vol. 49, iss. 2, pp. 194–201. https://doi.org/10.1016/j.toxicon.2006.09.014Richards K. L., Milligan C., Richardson R. J., Jancovski N., Grunnet M., Jacobson L. H., Undheim E. A. B., Mobli M. Selective Nav1.1 activation rescues Dravet syndrome mice from seizures and premature death. Proceedings of the National Academy of Sciences, 2018, vol. 115, no. 34, pp. 8077–8085. https://doi.org/10.1073/pnas.1804764115Richards K. L., Milligan C., Richardson R. J., Jancovski N., Grunnet M., Jacobson L. H., Undheim E. A. B., Mobli M. Selective Nav1.1 activation rescues Dravet syndrome mice from seizures and premature death. Proceedings of the National Academy of Sciences, 2018, vol. 115, no. 34, pp. 8077–8085. https://doi.org/10.1073/pnas.1804764115Saez N. J., Mobli M., Bieri M., Chassagnon I. R., Malde A. K., Gamsjaeger R., Mark A. E., Gooley P. R., Rash L. D., King G. F. A dynamic pharmacophore drives the interaction between Psalmotoxin-1 and the putative drug target acid-sensing ion channel 1a. Molecular Pharmacology, 2011, vol. 80, iss. 5, pp. 796–808. https://doi.org/10.1073/pnas.180476411510.1124/mol.111.072207Saez N. J., Mobli M., Bieri M., Chassagnon I. R., Malde A. K., Gamsjaeger R., Mark A. E., Gooley P. R., Rash L. D., King G. F. A dynamic pharmacophore drives the interaction between Psalmotoxin-1 and the putative drug target acid-sensing ion channel 1a. Molecular Pharmacology, 2011, vol. 80, iss. 5, pp. 796–808. https://doi.org/10.1073/pnas.180476411510.1124/mol.111.072207Saez N. J., Senff S., Jensen J. E., Er S. Y., Herzig V., Rash L. D., King G. F. Spider-venom peptides as therapeutics. Toxins, 2010, vol. 2, iss. 12, pp. 2851–2871. https://doi.org/10.3390/toxins2122851Saez N. J., Senff S., Jensen J. E., Er S. Y., Herzig V., Rash L. D., King G. F. Spider-venom peptides as therapeutics. Toxins, 2010, vol. 2, iss. 12, pp. 2851–2871. https://doi.org/10.3390/toxins2122851Schanbacher F. L., Lee C. K., Wilson I. B., Howell D. E., Odell G. V. Purification and characterization of tarantula, Dugesiella hentzi (Girard) venom hyaluronidase. Comparative Biochemistry &Physiology, 1973, vol. 44, iss. 2, pp. 389–396.Schanbacher F. L., Lee C. K., Wilson I. B., Howell D. E., Odell G. V. Purification and characterization of tarantula, Dugesiella hentzi (Girard) venom hyaluronidase. Comparative Biochemistry &Physiology, 1973, vol. 44, iss. 2, pp. 389–396.Siemens J., Zhou S., Piskorowski R., Nikai T., Lumpkin E. A., Basbaum A. I., King D., Julius D. Spider toxins activate the capsaicin receptor to produce inflammatory pain. Nature, 2006, vol. 444, pp. 208–212.Siemens J., Zhou S., Piskorowski R., Nikai T., Lumpkin E. A., Basbaum A. I., King D., Julius D. Spider toxins activate the capsaicin receptor to produce inflammatory pain. Nature, 2006, vol. 444, pp. 208–212.Suchyna T. M., Johnson J. H., Hamer K., Joseph F., Leykam D. A., Gage H. F., Clive C., Baumgarten M., Sachs F. Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. Journal of General Physiology, 2000, vol. 115, iss. 5, pp. 583–598. https://doi.org/10.1085/jgp.115.5.583Suchyna T. M., Johnson J. H., Hamer K., Joseph F., Leykam D. A., Gage H. F., Clive C., Baumgarten M., Sachs F. Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. Journal of General Physiology, 2000, vol. 115, iss. 5, pp. 583–598. https://doi.org/10.1085/jgp.115.5.583Swartz K. J., MacKinnon R. Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites. Neuron, 1997, vol. 18, iss. 4, pp. 665–673. https://doi.org/10.1016/s0896-6273(00)80306-2Swartz K. J., MacKinnon R. Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites. Neuron, 1997, vol. 18, iss. 4, pp. 665–673. https://doi.org/10.1016/s0896-6273(00)80306-2Takahashi H., Kim J. I., Min H. J., Sato K., Swartz K. J., Shimada I. Solution structure of hanatoxin1, a gating modifier of voltage-dependent K+ channels: Common surface features of gating modifier toxins. Journal of Molecular Biology, 2000, vol. 297, iss. 3, pp. 771–780. https://doi.org/10.1006/jmbi.2000.3609Takahashi H., Kim J. I., Min H. J., Sato K., Swartz K. J., Shimada I. Solution structure of hanatoxin1, a gating modifier of voltage-dependent K+ channels: Common surface features of gating modifier toxins. Journal of Molecular Biology, 2000, vol. 297, iss. 3, pp. 771–780. https://doi.org/10.1006/jmbi.2000.3609Takeuchi K., Park E. J., Lee C. W., Takeuchi K., Park E. J., Lee C. W., Kim J. I., Takahashi H., Swartz K. J., Shimada I. Solution structure of ω-grammotoxin SIA, a gating modifier of P/Q and N-type Ca2+ channel. Journal of Molecular Biology, 2002, vol. 321, iss. 3, pp. 517–526. https://doi.org/10.1016/s0022-2836(02)00595-8Takeuchi K., Park E. J., Lee C. W., Takeuchi K., Park E. J., Lee C. W., Kim J. I., Takahashi H., Swartz K. J., Shimada I. Solution structure of ω-grammotoxin SIA, a gating modifier of P/Q and N-type Ca2+ channel. Journal of Molecular Biology, 2002, vol. 321, iss. 3, pp. 517–526. https://doi.org/10.1016/s0022-2836(02)00595-8Tilley D. C., Angueyra J. M., Eum K. S., Kim H., Chao L.H., Peng A.W., Sack J.T. The tarantula toxin GxTx detains K+ channel gating charges in their resting conformation. Journal of General Physiology, 2019, vol. 151, iss. 3, pp. 292–315. https://doi.org/10.1085/jgp.201812213Tilley D. C., Angueyra J. M., Eum K. S., Kim H., Chao L.H., Peng A.W., Sack J.T. The tarantula toxin GxTx detains K+ channel gating charges in their resting conformation. Journal of General Physiology, 2019, vol. 151, iss. 3, pp. 292–315. https://doi.org/10.1085/jgp.201812213Vassilevski A. A., Kozlov S. A., Grishin E. V. Molecular diversity of spider venom. Biochemistry, 2009, vol. 74, no. 13, pp. 1505–1534. https://doi.org/10.1134/S0006297909130069Vassilevski A. A., Kozlov S. A., Grishin E. V. Molecular diversity of spider venom. Biochemistry, 2009, vol. 74, no. 13, pp. 1505–1534. https://doi.org/10.1134/S0006297909130069Whittaker R. H., Feeny P. P. Allelochemics: Chemical interactions between species. Science, 1971, vol. 17, no. 3973, pp. 757–770. https://doi.org/10.1126/science.171.3973.757Whittaker R. H., Feeny P. P. Allelochemics: Chemical interactions between species. Science, 1971, vol. 17, no. 3973, pp. 757–770. https://doi.org/10.1126/science.171.3973.757Wigger E., Kuhn-Nentwig L., Nentwig W. The venom optimisation hypothesis: A spider injects large venom quantities only into difficult prey types. Toxicon, 2002, vol. 40, iss. 6, pp. 749–752. https://doi.org/10.1016/s0041-0101(01)00277-xWigger E., Kuhn-Nentwig L., Nentwig W. The venom optimisation hypothesis: A spider injects large venom quantities only into difficult prey types. Toxicon, 2002, vol. 40, iss. 6, pp. 749–752. https://doi.org/10.1016/s0041-0101(01)00277-xWorld Spider Catalog. Version 25.0. Bern, Natural History Museum, 2024. Available at: http://wsc.nmbe.ch/ (accessed January 21, 2024). https://doi.org/10.24436/2World Spider Catalog. Version 25.0. Bern, Natural History Museum, 2024. Available at: http://wsc.nmbe.ch/ (accessed January 21, 2024). https://doi.org/10.24436/2Wright Z. V. F., McCarthy S., Dickman R., Reyes F. E., Sanchez-Martinez S., Cryar A., Kilford I., Hall A. The role of disulfide bond replacements in analogues of the tarantula toxin ProTxII and their effects on inhibition of the voltage-gated sodium ion channel Nav1.7. J. Journal of the American Chemical Society, 2017, vol. 139, no. 37, pp. 13063–13075. https://doi.org/10.1021/jacs.7b06506Wright Z. V. F., McCarthy S., Dickman R., Reyes F. E., Sanchez-Martinez S., Cryar A., Kilford I., Hall A. The role of disulfide bond replacements in analogues of the tarantula toxin ProTxII and their effects on inhibition of the voltage-gated sodium ion channel Nav1.7. J. Journal of the American Chemical Society, 2017, vol. 139, no. 37, pp. 13063–13075. https://doi.org/10.1021/jacs.7b06506Xiao Y., Tang J., Hu W., Xie J., Maertens C., Tytgat J., Liang S. Jingzhaotoxin-I, a novel spider neurotoxin preferentially inhibiting cardiac sodium channel inactivation. Journal of Biological Chemistry, 2004, vol. 280, iss. 13, pp. 12069–12076. https://doi.org/10.1074/jbc.m411651200Xiao Y., Tang J., Hu W., Xie J., Maertens C., Tytgat J., Liang S. Jingzhaotoxin-I, a novel spider neurotoxin preferentially inhibiting cardiac sodium channel inactivation. Journal of Biological Chemistry, 2004, vol. 280, iss. 13, pp. 12069–12076. https://doi.org/10.1074/jbc.m411651200Yuan C. H., He Q. Y., Peng K., Diao J.-B., Jiang L.-P., Tang X., Liang S.-P. Discovery of a distinct superfamily of Kunitz-type toxin (KTT) from tarantulas. PLoS ONE, 2008, vol. 3, no. 10, article no. e3414. https://doi.org/10.1371/journal.pone.0003414Yuan C. H., He Q. Y., Peng K., Diao J.-B., Jiang L.-P., Tang X., Liang S.-P. Discovery of a distinct superfamily of Kunitz-type toxin (KTT) from tarantulas. PLoS ONE, 2008, vol. 3, no. 10, article no. e3414. https://doi.org/10.1371/journal.pone.0003414

The authors declare that there are no conflicts of interest present.