Long (4 C-C) scorpion toxin superfamily, Sodium channel inhibitor family, Beta subfamily

General Scorpion βtoxins bind to site 4 of voltage-gated sodium channels (Nav), specifically the extracellular loop of segments S3-S4 of domain II. These toxins trap segment S4, keeping it in the activated position. This interaction induces a shift in the voltage dependence of Nav activation in the hyperpolarizing direction, and a reduction in the sodium peak amplitude (Cestele and Catterall, 2000 ).

This group of toxins can be sub-divided into four categories (Bosmans et al., 2007 ): β-m toxins that selectively act on mammalian Nav channels (e.g. Css2, Cll2 and Cn2 ), β-i toxins that selectively act on insect Nav channels (e.g. AaHIT1, LqqIT1, BmKIT1, Bj-xtrIT and AaBTX-L1 ), β-like toxins that act on both mammalian and insect Nav channels (e.g. Ts1, and Lqhb1 ), and *β
α* toxins that have the primary structure of β-toxins, but exhibit a functional α-effect (e.g. Cn12 ).