Title: A subfamily of acidic alpha-K(+) toxins
Authors: Huys, Isabelle ×
Olamendi-Portugal, Timoteo
Garcia-Gómez, Blanca Ines
Vandenberghe, Isabel
Van Beeumen, Jozef
Dyason, Karin
Clynen, Elke
Zhu, Shunyi
van der Walt, Jurg
Possani, Lourival D
Tytgat, Jan #
Issue Date: Jan-2004
Series Title: Journal of Biological Chemistry vol:279 issue:4 pages:2781-2789
Abstract: Three homologous acidic peptides have been isolated from the venom of three different Parabuthus scorpion species, P. transvaalicus, P. villosus, and P. granulatus. Analysis of the primary sequences reveals that they structurally belong to subfamily 11 of short chain alpha-K(+)-blocking peptides (Tytgat, J., Chandy, K. G., Garcia, M. L., Gutman, G. A., Martin-Eauclaire, M. F., van der Walt, J. J., and Possani, L. D. (1999) Trends Pharmacol. Sci. 20, 444-447). These toxins are 36-37 amino acids in length and have six aligned cysteine residues, but they differ substantially from the other alpha-K(+) toxins because of the absence of the critical Lys(27) and their total overall negative charge. Parabutoxin 1 (PBTx1), which has been expressed by recombinant methods, has been submitted to functional characterization. Despite the lack of the Lys(27), this toxin blocks several Kv1-type channels heterologously expressed in Xenopus oocytes but with low affinities (micromolar range). Because a relationship between the biological activity and the acidic residue substitutions may exist, we set out to elucidate the relative impact of the acidic character of the toxin and the lack of the critical Lys(27) on the weak activity of PBTx1 toward Kv1 channels. To achieve this, a specific mutant named rPBTx1 T24F/V26K was made recombinantly and fully characterized on Kv1-type channels heterologously expressed in Xenopus oocytes. Analysis of rPBTx1 T24F/V26K displaying an affinity toward Kv1.2 and Kv1.3 channels in the nanomolar range shows the importance of the functional dyad above the acidic character of this toxin.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Animal Physiology and Neurobiology Section - miscellaneous
Toxicology and Pharmacology
Research Centre for Pharmaceutical Care and Pharmaco-economics (-)
Research Unit KU Leuven Centre for IT & IP Law (CiTiP)
× corresponding author
# (joint) last author

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