CboK7
Scorpion toxin
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Through Potassium
Etymology
This toxin is known by two names: CboK7 and α-KTx 2.24.
The name CboK7 comes from the species the toxin was found in, C. bonito. K denotes the fact that the toxin affects potassium channels. Seven of these toxins were found in the venom of C. bonito, and this toxin was given the number 7.
The name α-KTx 2.24 is based on another naming system; scorpion toxins that affect potassium channels are referred to as KTx, and further classified with a Greek letter into one of the seven existing subfamilies, with this toxin belonging to the alpha family, which is characterized by a short chain and having three or four disulfide bridges.
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Chemistry
Family
Centruroides bonito is found in the Mexican state Guerrero. The venom of C. bonito has seven different peptides, CboK1 to CboK7. These seven toxins are part of the α-KTx family (parabutoxin), whose family members have very low pH values.
Structure
CboK7 consists of 39 amino acid residues and weighs 4,365 Da.
All CboK peptides contain a functional dyad of Lys and Tyr. The functional dyad refers to a pair of amino acid residues in toxins that target Kv1 channels, which plays a key role in toxin-binding. It typically consists of a lysine residue paired with a hydrophobic residue, such as tyrosine, phenylalanine or leucine.
Sequence: TFINVKCTSPKQCLKPCKDLYGPHAGEKCMNGKCKCYKV
Homology
CboK7 varies from CboK3 and CboK4 by one amino acid. Specifically, CboK7 has Phe instead of Ile in CboK3 and Val instead of Pro in CboK4.
Target & mode of action
CboK7 toxin affects voltage-gated potassium channels. It is capable of completely blocking Kv1.2 type channels, with a high affinity (Kd = 24 pM), and it can partially inhibit Kv1.1 and Kv1.3 channels with a lower affinity (Kd = 141 nM and 20.4 nM, respectively).
The blocking occurs by the binding of CboK7 to the potassium channel. Specifically, its lysine residue blocks the selectivity filter, which is the part of the channel that is structured in a way that allows only K+ ions to pass through. Blocking this filter prevents the flow of ions through the channel.
The impact of CboK7 on humans has not yet been reported, but the typical symptoms of Centruroides genus venom poisoning are known.