门控修饰毒素揭示了电压门控钙通道和钾通道中一个保守的结构基序。
Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels.
作者信息
Li-Smerin Y, Swartz K J
机构信息
Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8585-9. doi: 10.1073/pnas.95.15.8585.
Protein toxins from venomous animals exhibit remarkably specific and selective interactions with a wide variety of ion channels. Hanatoxin and grammotoxin are two related protein toxins found in the venom of the Chilean Rose Tarantula, Phrixotrichus spatulata. Hanatoxin inhibits voltage-gated K+ channels and grammotoxin inhibits voltage-gated Ca2+ channels. Both toxins inhibit their respective channels by interfering with normal operation of the voltage-dependent gating mechanism. The sequence homology of hanatoxin and grammotoxin, as well as their similar mechanism of action, raises the possibility that they interact with the same region of voltage-gated Ca2+ and K+ channels. Here, we show that each toxin can interact with both voltage-gated Ca2+ and K+ channels and modify channel gating. Moreover, mutagenesis of voltage-gated K+ channels suggests that hanatoxin and grammotoxin recognize the same structural motif. We propose that these toxins recognize a voltage-sensing domain or module present in voltage-gated ion channels and that this domain has a highly conserved three-dimensional structure.
来自有毒动物的蛋白质毒素与多种离子通道表现出显著的特异性和选择性相互作用。哈那毒素（Hanatoxin）和格玛毒素（grammotoxin）是在智利玫瑰狼蛛（Phrixotrichus spatulata）毒液中发现的两种相关蛋白质毒素。哈那毒素抑制电压门控钾通道，格玛毒素抑制电压门控钙通道。两种毒素均通过干扰电压依赖性门控机制的正常运作来抑制各自的通道。哈那毒素和格玛毒素的序列同源性以及它们相似的作用机制，增加了它们与电压门控钙通道和钾通道的同一区域相互作用的可能性。在此，我们表明每种毒素都能与电压门控钙通道和钾通道相互作用并改变通道门控。此外，电压门控钾通道的诱变表明哈那毒素和格玛毒素识别相同的结构基序。我们提出这些毒素识别存在于电压门控离子通道中的电压传感结构域或模块，并且该结构域具有高度保守的三维结构。
Zotero 插件