Loret E P, del Valle R M, Mansuelle P, Sampieri F, Rochat H
Laboratoire de Biochimie, CNRS URA 1455, Faculté de Médecine, Secteur Nord, Marseille, France.
J Biol Chem. 1994 Jun 17;269(24):16785-8.
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.
特定种类的海葵毒素和蝎子毒素在哺乳动物可兴奋膜的电压门控钠通道的同一药理学位点上存在竞争。然而，这些蝎子毒素和海葵毒素是两个不同的蛋白质家族。在此，我们纯化并测序了一种对哺乳动物具有高毒性的新海葵毒素Bg II，以及一种毒性较小的突变体Bg III。根据与两种海葵毒素二维核磁共振结构的序列同源性确定了两种Bg II模型。只有一种模型符合从Bg II获得的圆二色性数据，并与一种蝎子毒素的X射线结构进行了比较。两种结构的比较表明，海葵毒素和蝎子毒素中有5个氨基酸残基的位置相似。在这5个残基中，有4个是碱性残基，在这些毒素的表面构成两个不同的带正电荷的极点。在分离出的海葵突变体中，其中一个正极点旁边的负电荷降低了毒性。这些结果表明，带正电荷的氨基酸残基可能对这些毒素的活性至关重要，并概述了静电键在海葵毒素和蝎子毒素与其受体相互作用中的作用。
