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The scorpion toxins are the largest potassium channel-blocking peptide family. The understanding of toxin binding interfaces is usually restricted by two classical binding interfaces: one is the toxin α-helix motif, the other is the antiparallel β-sheet motif.
In this review, such traditional knowledge was updated by another two different binding interfaces: one is BmKTX toxin using the
turn motif between the α-helix and antiparallel β-sheet domains as the binding interface, the other is Ts toxin using turn motif between the β-sheet in the N-terminal and α-helix domains as the binding interface. Their interaction analysis indicated that the scarce
negatively charged residues in the scorpion toxins played a critical role in orientating the toxin binding interface. In view of the toxin
negatively charged amino acids as “binding interface regulator”, the law of scorpion toxin-potassium channel interaction was proposed, that is, the polymorphism of negatively charged residue distribution determines the diversity of toxin binding interfaces. Such
law was used to develop scorpion toxin-potassium channel recognition control technique. According to this technique, three Kv1.3
channel-targeted peptides, using BmKTX as the template, were designed with the distinct binding interfaces from that of BmKTX
through modulating the distribution of toxin negatively charged residues. In view of the potassium channel as the common targets of
different animal toxins, the proposed law was also shown to helpfully orientate the binding interfaces of other animal toxins. Clearly,
the toxin-potassium channel interaction law would strongly accelerate the research and development of different potassium channelblocking animal toxins in the future.
Binding Modes of Two Scorpion Toxins to the Voltage-Gated Potassium Channel Kv1.3 Revealed from Molecular Dynamics
