PEPTIDES AND GENES FROM Centruroides noxius SCORPION THAT AFFECT THE FUNCTION OF ERG K⁺-CHANNELS

Zamudio, F.(1), Corona, M.(1), Pardo, L.(1), Gurrola, G.(1), Scaloni, A.(2), Possani, L.D.(1)

(1)Department of Molecular Recognition and Structural Biology, Institute of Biotechnology, Universidad Nacional Autonoma de Mexico, Av. Universidad, 2001 Apartado Postal 510-3, Cuernavaca 62210, MEXICO, (2)I.A.B.B.A.M. Centro Internazionale Servizi di Spettrometia di Massa, CNR, Naples 80147, Italy

Ergtoxin-1 (ErgTx1) is the first example of a scorpion toxin that inhibits specifically only the Erg K⁺-channels (Gurrola et al., FASEB J. 13:953-962, 1999). We discovered that a family of similar peptides is present in the same venomous gland of the Mexican scorpion Centruroides noxius Hoffmann. At least, seven peptides and genes were cloned from this scorpion. They all contain four disulfide bridges, having either 42 or 43 amino acid residues, whose primary structure similarities varies from 76 to 97% identity. The Kdof Ergtx1 examined in Xenopus laevis oocytes expressing the human hypothalamic Erg-channels (HERG) was shown to be in the order of 7 nM, whereas that of ErgTx2 was 1.2 uM. Oxidation of the Met35 of ErgTx1 decreased by almost 4 orderof magnitudes its affinity for HERG-channels, heterologously expressed in the oocyte model. This chemical modification is indicative of the possible location of the active site of this toxin when interacting with HERG-channels.

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

CORRESPONDENCE TO:

Fernando Zamudio, Av. Universidad, 2001, Col. Chamilpa, Cuernavaca, Mexico, 62210, Email: zam@ibt.unam.mx