Title: Evolutionary trace analysis of scorpion toxins specific for K-channels
Authors: Zhu, Shunyi ×
Huys, Isabelle
Dyason, Karin
Verdonck, Alfons
Tytgat, Jan #
Issue Date: Feb-2004
Publisher: Wiley-liss
Series Title: Proteins vol:54 issue:2 pages:361-70
Abstract: Scorpion alpha-K(+) channel toxins are a large family of polypeptides with a similar structure but diverse pharmacological activities. Despite many structural and functional data available at present, little progress has been made in understanding the toxin's molecular basis responsible for the functional diversification. In this paper, we report the first complete cDNA sequences of toxins belonging to subfamily 6 and identify five new members, called alpha-KTx 6.6-6.10. By analyzing the rates of mutations that occurred in the corresponding cDNAs, we suggest that accelerated evolution in toxin-coding regions may be associated with the functional diversification of this subfamily. To pinpoint sites probably involved in the functional diversity of alpha-KTx family, we analyzed this family of sequences using the evolutionary trace method. This analysis highlighted one channel-binding surface common for all the members. This surface is composed of one conserved lysine residue at position 29 assisted by other residues at positions 10, 26, 27, 32, 34, and 36. Of them, the positions 29, 32, and 34 have been reported to be the most major determinants of channel specificity. Interestingly, another contrary surface was also observed at a higher evolutionary time cut-off value, which may be involved in the binding of ERG (ether-a-go-go-related gene) channel-specific toxins. The good match between the trace residues and the functional epitopes of the toxins suggested that the evolutionary trace results reported here can be applied to predict channel-binding sites of the toxins. Because, the side-chain variation in the trace positions is strongly linked with the functional alteration and channel-binding surface transfer of alpha-KTx family, we conclude that our findings should also be important for the rational design of new toxins targeting a given potassium channel with high selectivity.
ISSN: 0887-3585
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Toxicology and Pharmacology
Interdisciplinary Research Facility Life Sciences, Campus Kulak Kortrijk
Research Centre for Pharmaceutical Care and Pharmaco-economics (-)
Faculty of Medicine - miscellaneous
× corresponding author
# (joint) last author

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