A New Peptide from the Venom of the Madagascar Cat-Eyed Snake  Madagascarophis colubrinus  Blocks Nicotinic Acetylcholine Receptor

E. V. Kryukova; Крюкова Е. В.; D. A. Ivanov; Иванов Д. А.; N. V. Kopylova; Копылова Н. В.; V. G. Starkov; Старков В. Г.; T. V. Andreeva; Андреева Т. В.; I. A. Ivanov; Иванов И. А.; V. I. Tsetlin; Цетлин В. И.; Yu. N. Utkin; Уткин Ю. Н.

doi:10.31857/S0132342323030156

A New Peptide from the Venom of the Madagascar Cat-Eyed Snake Madagascarophis colubrinus Blocks Nicotinic Acetylcholine Receptor

Authors: Kryukova E.V.¹, Ivanov D.A.², Kopylova N.V.¹, Starkov V.G.¹, Andreeva T.V.¹, Ivanov I.A.¹, Tsetlin V.I.¹, Utkin Y.N.¹
Affiliations:
1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences
2. FKOO “Labkorp”
Issue: Vol 49, No 3 (2023)
Pages: 296-305
Section: Articles
URL: https://rjmseer.com/0132-3423/article/view/670619
DOI: https://doi.org/10.31857/S0132342323030156
EDN: https://elibrary.ru/PDSQUE
ID: 670619

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Abstract

In screening the venoms of various snake species, we found that the venom of the Madagascar cat-eyed snake Madagascarophis colubrinus competes with α-bungarotoxin for binding to the nicotinic acetylcholine receptor from Torpedo californica. Using liquid chromatography, a peptide, called macoluxin and inhibiting the binding of the toxin to the receptor, was isolated from the venom. The amino acid sequence of this 23-amino acid peptide was determined by automatic Edman degradation. Comparison with amino acid sequences of known proteins showed that the macoluxin sequence is homologous to the α-helical region of the sequence of snake venom metalloproteinases. The peptide was synthesized by solid-phase peptide synthesis, and the study of its biological activity showed that it inhibits the binding of α-bungarotoxin to the Torpedo receptor with an IC₅₀ of 47 μM. Macoluxin also reversibly inhibited acetylcholine-induced currents in the muscle-type nicotinic acetylcholine receptor. This is the first data on the presence in the venom of rear fanged snakes of a peptide that can inhibit the nicotinic acetylcholine receptor.

Keywords

Madagascar cat-eyed snake, venom, nicotinic acetylcholine receptor, peptide, inhibitor, macoluxin

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