Positively charged amino acid residues located similarly in sea anemone and scorpion toxins.
Specific groups of sea anemone and scorpion toxins compete on the same pharmacological site, on the voltage-gated sodium channel of mammal excitable membranes. However, these scorpion and sea anemone toxins are two distinct protein families. Here we purified and sequenced a new sea anemone toxin, Bg II, highly toxic to mammals and also a less toxic mutant, Bg III. Two Bg II models were determined from sequence homologies with two sea anemone toxin two-dimensional NMR structures. Only one model conformed to circular dichroism data obtained from Bg II and was compared with an x-ray structure of a scorpion toxin. The comparison of the two structures shows that 5 amino acid residues are located similarly in the sea anemone toxin and the scorpion toxin. From these 5 residues, 4 are basic residues, constituting two distinct positively charged poles on the surface of these toxins. In the sea anemone mutant isolated, a negative charge beside one of the positive poles decreases the toxicity. These results show that positively charged amino acid residues could be essential for the activity of these toxins and outline the role of electrostatic bonds in the interaction of sea anemone and scorpion toxins with their receptor.
Loret
E P
EP
Laboratoire de Biochimie, CNRS URA 1455, Faculté de Médecine, Secteur Nord, Marseille, France.
del Valle
R M
RM
Mansuelle
P
P
Sampieri
F
F
Rochat
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003064:Cnidarian Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012604:Scorpion Venoms / Q000737:chemistry* / Q000633:toxicity; D012605:Scorpions; D012615:Sea Anemones; D017386:Sequence Homology, Amino Acid; D014961:X-Ray Diffraction
D003064:Cnidarian Venoms; D012604:Scorpion Venoms; C087690:BG III toxin; C087689:Bg II toxin