Voltage-gated potassium (K) channels regulate diverse physiological processes and are an important target for developing novel therapeutic approaches. Sea anemone (Cnidaria， Anthozoa) venoms comprise a highly complex mixture of peptide toxins with diverse and selective pharmacology on K channels. From the nematocysts of the sea anemone ， a peptide that we named AbeTx1 was purified and functionally characterized on 12 different subtypes of K channels (K1.1?K1.6; K2.1; K3.1; K4.2; K4.3; K11.1; and， Shaker IR)， and three voltage-gated sodium channel isoforms (Na1.2， Na1.4， and BgNa). AbeTx1 was selective for Shaker-related K? channels and is capable of inhibiting K? currents， not only by blocking the... More
Voltage-gated potassium (K) channels regulate diverse physiological processes and are an important target for developing novel therapeutic approaches. Sea anemone (Cnidaria， Anthozoa) venoms comprise a highly complex mixture of peptide toxins with diverse and selective pharmacology on K channels. From the nematocysts of the sea anemone ， a peptide that we named AbeTx1 was purified and functionally characterized on 12 different subtypes of K channels (K1.1?K1.6; K2.1; K3.1; K4.2; K4.3; K11.1; and， Shaker IR)， and three voltage-gated sodium channel isoforms (Na1.2， Na1.4， and BgNa). AbeTx1 was selective for Shaker-related K? channels and is capable of inhibiting K? currents， not only by blocking the K? current of K1.2 subtype， but by altering the energetics of activation of K1.1 and K1.6. Moreover， experiments using six synthetic alanine point-mutated analogs further showed that a ring of basic amino acids acts as a multipoint interaction for the binding of the toxin to the channel. The AbeTx1 primary sequence is composed of 17 amino acids with a high proportion of lysines and arginines， including two disulfide bridges (Cys1?Cys4 and Cys2?Cys3)， and it is devoid of aromatic or aliphatic amino acids. Secondary structure analysis reveals that AbeTx1 has a highly flexible， random-coil-like conformation， but with a tendency of structuring in the beta sheet. Its overall structure is similar to open-ended cyclic peptides found on the scorpion κ-KTx toxins family， cone snail venoms， and antimicrobial peptides.
