THE SUB-FAMILY OF K⁺-CHANNEL ERG-LIKE TOXINS ISOLATED FROM SCORPION VENOMS

Possani, L.D.(1), Corona, M. (1), Gurrola, G.B. (1), García-Gómez, B.I. (1), Pardo, L. (1), Merino, E. (1), Enzo, W.(1,2) 

(1)Institute of Biotechnology, Universidad Nacional Autonoma de Mexico, Av. Universidad, 2001 Apartado Postal 510-3, Cuernavaca 62210, MEXICO. (2)Department of Biotechnology and Biosciences, University of Milano-Bococca, I-20126 Milano, Italy

Ergtoxin-1 (ErgTx1) was shown to inhibit specifically K+-channels of the ether-a-go-go-related genes (Gurrola et al., FASEB J. 13:953-962, 1999). This peptide contains 42 amino acid residues compacted by four disulfide bridges (Scaloni et al., FEBS Lett. 479:156-157, 2000). At least 23 distinct peptides and/or genes were obtained from venomous glands of Mexican scorpions of the species: Centruroides (C.) noxius, C. limpidus limpidus, C. sculpturatus and C. gracilis. They all contain four disulfide bridges, having between 42 to 47 amino acid residues. A phylogenetic tree constructed with the primary structure of these peptides shows that they might conform four different structural groups, and according to the international classification proposed (Tytgat et al., Trends  Pharm. Sci. 20:444-447 1999) these scorpion peptides constitute a new sub-family (-KTx). The physiological effect of ErgTx1 was thoroughly studied recently using side-directed mutants of the human hypothalamic ERG-channels expressed in Xenopus laevis oocytes (Pardo et al. J.Biol. Chem. 277:16403-16411, 2002). ErgTx1 is a true channel blocker, interacting directly with amino acids situated in between the S5 and S6 segment of the channel. The effect of ErgTx2 was recently assayed on K+-currents of lactrotropic cells (Lecchi et al., J. Neurosci. 22:3414-3425, 2002). The slowly deactivating long-lasting component (IERGS) is inhibited by ErgTx2. Some of the other peptides belonging to this sub-family also affect ERG-channels, with different affinities. However, most of the sequences obtained are still at the stage of research, for which we know the coding gene, but thus far have not obtained the pure peptide, for direct assay.

Acknowledgements: Supported in part by grants from DGAPA-UNAM (IN216900), CONACyT (31691-N and Z-005) and Howard Hughes Medical Institute (55000574) to LDP. EW holds a chair from CONACyt.

CORRESPONDENCE TO:

Possani, L.D., Institute of Biotechnology, Universidad NacionalAutonoma de Mexico, Av. Universidad, 2001 Apartado Postal 510-3, Cuernavaca62210 – MEXICO, Email: possani@ibt.unam.mx