Scorpion toxins interact with nicotinic acetylcholine receptors
Kasheverov I. E., Oparin P. B., Zhmak M. N., Egorova N. S., Ivanov I. A., Gigolaev A. M., Nekrasova O. V., Serebryakova M. V., Kudryavtsev D. S., Prokopev N. A., Hoang A. N., Tsetlin V. I., Vassilevski A. A., Utkin Y. N.
FEBS Letters
Vol.593, Issue19, P. 2779-2789
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1002/1873-3468.13530
Аннотация:
Neurotoxins are among the main components of scorpion and snake venoms. Scorpion neurotoxins affect voltage-gated ion channels, while most snake neurotoxins target ligand-gated ion channels, mainly nicotinic acetylcholine receptors (nAChRs). We report that scorpion venoms inhibit α-bungarotoxin binding to both muscle-type nAChR from Torpedo californica and neuronal human α7 nAChR. Toxins inhibiting nAChRs were identified as OSK-1 (α-KTx family) from Orthochirus scrobiculosus and HelaTx1 (κ-KTx family) from Heterometrus laoticus, both being blockers of voltage-gated potassium channels. With an IC50 of 1.6 μm, OSK1 inhibits acetylcholine-induced current through mouse muscle-type nAChR heterologously expressed in Xenopus oocytes. Other well-characterized scorpion toxins from these families also bind to Torpedo nAChR with micromolar affinities. Our results indicate that scorpion neurotoxins present target promiscuity. © 2019 Federation of European Biochemical Societies
Ключевые слова:
neurotoxin; nicotinic acetylcholine receptor; potassium channels; scorpion; snake; venom
alpha bungarotoxin; bungarotoxin receptor; nicotinic receptor; scorpion venom; voltage gated potassium channel; nicotinic receptor; nicotinic receptor blocking agent; protein binding; scorpion venom; adult; Article; binding affinity; controlled study; Heterometrus laoticus; IC50; nonhuman; oocyte; Orthochirus scrobiculosus; priority journal; protein binding; protein expression; protein interaction; scorpion; Torpedo californica; Xenopus; animal; chemistry; classification; metabolism; mouse; Animals; Mice; Nicotinic Antagonists; Protein Binding; Receptors, Nicotinic; Scorpion Venoms; Xenopus
Язык текста: Английский
ISSN: 1873-3468
Kasheverov I. E. Igor` Evgenyevich 1966-
Oparin P. B.
Zhmak M. N.
Egorova N. S.
Ivanov I. A.
Gigolaev A. M.
Nekrasova O. V.
Serebryakova M. V.
Kudryavtsev D. S.
Prokopev N. A.
Hoang A. N.
Tsetlin V. I.
Vassilevski A. A.
Utkin Y. N.
Кашеверов И. Е. Игорь Евгеньевич 1966-
Опарин П. Б.
Жмак М. Н.
Егорова Н. С.
Иванов И. А.
Гиголаев А. М.
Некрасова О. В.
Серебрякова М. В.
Кудрявцев Д. С.
Прокопев Н. А.
Хоанг А. Н.
Цетлин В. И.
Вассилевски А. А.
Уткин Y. Н.
Scorpion toxins interact with nicotinic acetylcholine receptors
Текст визуальный непосредственный
FEBS Letters
Elsevier Science Publisher B.V.
Vol.593, Issue19 P. 2779-2789
2019
Статья
neurotoxin nicotinic acetylcholine receptor potassium channels scorpion snake venom
alpha bungarotoxin bungarotoxin receptor nicotinic receptor scorpion venom voltage gated potassium channel nicotinic receptor nicotinic receptor blocking agent protein binding scorpion venom adult Article binding affinity controlled study Heterometrus laoticus IC50 nonhuman oocyte Orthochirus scrobiculosus priority journal protein binding protein expression protein interaction scorpion Torpedo californica Xenopus animal chemistry classification metabolism mouse Animals Mice Nicotinic Antagonists Protein Binding Receptors, Nicotinic Scorpion Venoms Xenopus
Neurotoxins are among the main components of scorpion and snake venoms. Scorpion neurotoxins affect voltage-gated ion channels, while most snake neurotoxins target ligand-gated ion channels, mainly nicotinic acetylcholine receptors (nAChRs). We report that scorpion venoms inhibit α-bungarotoxin binding to both muscle-type nAChR from Torpedo californica and neuronal human α7 nAChR. Toxins inhibiting nAChRs were identified as OSK-1 (α-KTx family) from Orthochirus scrobiculosus and HelaTx1 (κ-KTx family) from Heterometrus laoticus, both being blockers of voltage-gated potassium channels. With an IC50 of 1.6 μm, OSK1 inhibits acetylcholine-induced current through mouse muscle-type nAChR heterologously expressed in Xenopus oocytes. Other well-characterized scorpion toxins from these families also bind to Torpedo nAChR with micromolar affinities. Our results indicate that scorpion neurotoxins present target promiscuity. © 2019 Federation of European Biochemical Societies