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“Kaliotoxin” - A high affinity blocker of the voltage-activate

In Animal Toxins : State of the Art - Perspectives in Health and Biotechnology (De Lima ME, Monteiro de Castro Pimenta A, Martin-Eauclaire MF, Zingali RB, Rochat H, eds) Belo Horizonte : Editora UFMG, 2009, pp. 179-192
“Kaliotoxin” - A high affinity blocker of the voltage-activated potassium channel Kv1.3
Martin-Eauclaire MF, Bougis PE

Voltage-gated potassium channels (Kv) play a key role in the regulation of a wide variety of physiological processes, including neuronal and cell excitability, the regulation of heart beat-rate, muscle contraction, neurotransmitter release, hormonal secretion, signal transduction and cell proliferation. Multiple combinations resulting from the ability of Kv channels subunits to coassemble dramatically increase the total number of functional distinct Kv channels. Peptide toxins from various animal venoms inhibit different subtypes of Kv channels by binding strongly (sometimes in the pM range) to the outer vestibule of the pore-region. They have been valuable tools for understanding the physiological role of Kv channels and have been exploited to gain insights into the structure of the channel pore that they occlude via electrostatic and hydrophobic interactions. Numerous studies have been conducted to understand the structure-function relationships of these Kv channel blockers. So far, about 100 different Kv channel toxins have been found in scorpion venoms and according to their primary structures and functions, they have been classified into four subfamilies, called α-, β-, γ-Ktx and κ-Ktx. At the 3D-level, these “short” peptides are only constituted by a common minimal structural motif, also found in the longer scorpion toxins active on the voltage-activated Na+ channels : i.e. one α-helix and an antiparallel β-sheet linked by two of their disulfide bridges. They possess at least two functionally crucial residues, as example a lysine, which plugs the channel pore and a hydrophobic residue, which strengthens the interaction between the toxin and its target. Among the first characterized and structurally defined scorpion toxins able to block Kv channels was kaliotoxin (KTX), which binds with high affinity (KD in a pM range) to the Kv1.3 channel. KTX was used extensively by different groups to characterize the 3D-structure of the pore-forming region and, recently, to illustrate significant conformational changes in both the toxin and the channel during the binding. In this review, we will summarize our current knowledge on KTX at the structural, biological and immunological level. Organization of the KTX gene and mRNA precursor will be also approached.


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