Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels
Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels
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DOI：
10.1073/pnas.95.15.8585
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发表时间：
1998-07-21
影响因子：
11.1
通讯作者：
Swartz, KJ
中科院分区：
文献类型：
--
作者：
Li-Smerin, Y;Swartz, KJ
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。Hanatoxin和grammotoxin是在智利玫瑰狼蛛Phrixotrichus spatulata的毒液中发现的与蛋白质毒素相关的毒素。Hanatoxin抑制电压门控K+通道，grammotoxin抑制电压门控Ca 2+通道。这两种毒素通过干扰电压依赖性门控机制的正常操作来抑制其各自的通道。花毒毒素和grammotoxin的序列同源性，以及它们相似的作用机制，提出了它们与电压门控Ca 2+和K+通道的相同区域相互作用的可能性。在这里，我们表明，每种毒素都可以与电压门控的Ca 2+和K+通道相互作用，并修改通道门控。此外，电压门控K+通道的突变表明，花毒毒素和grammotoxin识别相同的结构基序，我们建议，这些毒素识别电压敏感域或模块存在于电压门控离子通道，该域具有高度保守的三维结构。
Protein toxins from venomous animals exhibit remarkably specific and selective interactions with a wide variety of ion channels. Hanatoxin and grammotoxin are tno 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.