Scorpion toxins from Tityus cambridgei that affect Na(+)-channels.
By means of high performance liquid chromatography (HPLC) the soluble venom of the Amazonian scorpion Tityus cambridgei was fractionated into over 50 different components. Four toxic and/or lethal peptides to mice were obtained in pure form and sequenced. Mass spectrometry analysis showed molecular weights of 7310, 7151, 7259 and 7405, respectively, for toxins Tc48a, Tc49a, Tc54 and Tc49b. The N-terminal amino acid sequence was obtained for the three first toxins mentioned, whereas the full primary structure was determined for Tc49b. It contains 64 amino acid residues, closely packed by four disulfide bridges. Sequence comparison analysis showed similarities around 50% with other toxins from scorpions of the genus Tityus of Brazil. It is lethal to mice at doses of 20 microg per 20 g mouse. The toxin was shown to affect the Na(+)-currents permeability of rat cerebellum granular cells in culture. Almost a complete elimination of current was observed with 100 nM toxin concentration. This effect was partially reversible. Furthermore, this toxin does not modify the function of the Shaker B K(+)-channels expressed on Sf9 cells, nor does it modify the Na(+)-channel function in a similar manner as those reported for the alpha-scorpion toxins purified from other scorpions.
Batista
Cesar V F
CV
Department of Molecular Recognition and Structural Biology, Institute of Biotechnology-UNAM, Avenida Universidad, 2001, Apartado Postal 510-3, 62210, Cuernavaca, Mexico.
Zamudio
Fernando Z
FZ
Lucas
Sylvia
S
Fox
Jay W
JW
Frau
Andrea
A
Prestipino
Gianfranco
G
Possani
Lourival D
LD
D000595:Amino Acid Sequence; D000818:Animals; D001938:Brazil; D002460:Cell Line; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D007928:Lethal Dose 50; D013058:Mass Spectrometry; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry / Q000235:genetics / Q000633:toxicity*; D012605:Scorpions / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D015222:Sodium Channels