Tarantula toxins interact with voltage sensors within lipid membranes.

Tarantula toxins interact with voltage sensors within lipid membranes.
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DOI:
10.1085/jgp.200709869
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发表时间:
2007-11
期刊:
The Journal of general physiology
影响因子:
--
通讯作者:
Swartz KJ
Swartz KJ
中科院分区:
其他
文献类型:
--
作者:
Milescu M;Vobecky J;Roh SH;Kim SH;Jung HJ;Kim JI;Swartz KJ

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电压激活的离子通道对于电信号是必不可少的,然而电压感知的机制仍在深入研究中。电压传感器桨是电压激活的钾(Kv)通道中的一个重要结构基序,已被提出在蛋白质-脂质界面移动,以响应膜电压的变化。在这里,我们探讨是否狼蛛毒素,如hanatoxin和SGTx 1抑制Kv通道的相互作用与桨图案内的膜。我们发现,这些毒素可以在生理相关条件下分配到膜中,但毒素-膜相互作用不足以抑制KV通道。从诱变研究中,我们确定了参与结合的桨基序,和那些重要的膜相互作用的毒素的区域。用鞘磷脂酶D修饰膜显著改变了毒素通道复合物的稳定性,表明狼蛛毒素与膜内的桨基序相互作用,并且它们是脂质通道相互作用的灵敏检测器。
Voltage-activated ion channels are essential for electrical signaling, yet the mechanism of voltage sensing remains under intense investigation. The voltage-sensor paddle is a crucial structural motif in voltage-activated potassium (Kv) channels that has been proposed to move at the protein–lipid interface in response to changes in membrane voltage. Here we explore whether tarantula toxins like hanatoxin and SGTx1 inhibit Kv channels by interacting with paddle motifs within the membrane. We find that these toxins can partition into membranes under physiologically relevant conditions, but that the toxin–membrane interaction is not sufficient to inhibit Kv channels. From mutagenesis studies we identify regions of the toxin involved in binding to the paddle motif, and those important for interacting with membranes. Modification of membranes with sphingomyelinase D dramatically alters the stability of the toxin–channel complex, suggesting that tarantula toxins interact with paddle motifs within the membrane and that they are sensitive detectors of lipid–channel interactions.
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