Last decade update for three-finger toxins: Newly emerging structures and biological activities

Abstract

Three-finger toxins (TFTs) comprise one of largest families of snake venom toxins. While they are principal to and the most toxic components of the venoms of the Elapidae snake family, their presence has also been detected in the venoms of snakes from other families. The first TFT, α-bungarotoxin, was discovered almost 50 years ago and has since been used widely as a specific marker of the α7 and muscle-type nicotinic acetylcholine receptors. To date, the number of TFT amino acid sequences deposited in the UniProt Knowledgebase free-access database is more than 700, and new members are being added constantly. Although structural variations among the TFTs are not numerous, several new structures have been discovered recently; these include the disulfide-bound dimers of TFTs and toxins with nonstandard pairing of disulfide bonds. New types of biological activities have also been demonstrated for the well-known TFTs, and research on this topic has become a hot topic of TFT studies. The classic TFTs α-bungarotoxin and α-cobratoxin, for example, have now been shown to inhibit ionotropic receptors of γ-aminobutyric acid, and some muscarinic toxins have been shown to interact with adrenoceptors. New, unexpected activities have been demonstrated for some TFTs as well, such as toxin interaction with interleukin or insulin receptors and even TFT-activated motility of sperm. This minireview provides a summarization of the data that has emerged in the last decade on the TFTs and their activities.

Keywords: Three-finger toxins, Snake, Venom, Structure, Biological activity

Core tip: The three-finger toxins (TFTs) of snake venoms are principal to and the most toxic components of elapid venoms. Over 700 TFT amino acid sequences are listed in the UniProt Knowledgebase currently, with new members added constantly. The past decade has also seen multitudinous new discoveries, including structural variations in TFTs (i.e. disulfide-bound dimers), new types of biological activities for the well-known TFTs (e.g., α-bungarotoxin’s inhibition of ionotropic receptors of γ-aminobutyric acid), and other new, unexpected activities for the TFTs (i.e. interaction with interleukin or insulin receptors and activation of sperm motility). This minireview provides an up-to-date overview of these data.