Snake α-Neurotoxins with Different Affinity to Two Binding Sites of Muscle-Type Nicotinic Acetylcholine Receptors

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Abstract

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels composed of five homologous subunits that form a transmembrane ion pore. Depending on the composition of the subunits, there are pharmacologically different types of nAChRs. Muscle-type nAChRs contain two agonist-binding sites that differ in the composition of the subunits that form them. Both sites interact with high affinity with alpha-neurotoxins (α-NT) from snake venoms. Most α-NTs interact with both sites with equal affinity. However, there are several α-NTs that have different affinities for the two binding sites of muscle-type nAChRs. In this work, we found that neurotoxin I from the venom of the cobra Naja oxiana also distinguishes between the two binding sites in muscle-type nAChRs. Based on the analysis of known amino acid sequences of snake α-NT, several more toxins with such properties are expected. Toxins of this group can be used as molecular tools to study subtle differences in ligand recognition mechanisms at the binding sites of muscle-type nAChRs.

About the authors

E. V Kryukova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Moscow, Russia

V. I Tsetlin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Moscow, Russia

Yu. N Utkin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: utkin@ibch.ru
Moscow, Russia

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