Tarantula toxins use common surfaces for interacting with Kv and ASIC ion channels.
Tarantula toxins use common surfaces for interacting with Kv and ASIC ion channels.
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DOI：
10.7554/elife.06774
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发表时间：
2015-05-07
期刊：
影响因子：
7.7
通讯作者：
Swartz KJ
中科院分区：
文献类型：
--
作者：
Gupta K;Zamanian M;Bae C;Milescu M;Krepkiy D;Tilley DC;Sack JT;Yarov-Yarovoy V;Kim JI;Swartz KJ
狼蛛毒素结合在电压激活离子通道的电压敏感区域上，被认为是分割到膜上并结合到双层内的通道上。虽然结合在通道上的电压敏感型毒素的结构尚未解决，但最近发现了一种结构上的同系物，psalmoox1(PcTx1)，它与酸敏离子通道(ASIC)的胞外结构域形成了复合体。在本研究中，我们使用光谱、生物物理和计算方法比较了PcTx1和电压敏感型毒素广西毒(GxTx-1E)的膜相互作用性质和通道结合表面。我们的结果表明，这两种类型的狼蛛毒素都与膜相互作用，但电压传感器毒素在双层中分配得更深。此外，我们的结果表明，狼蛛毒素已经进化出类似的凹面，用于夹住α-螺旋，这在水或脂类物理环境中是有效的。Http://dx.doi.org/10.7554/eLife.06774.001：像狼蛛或蝎子这样的有毒动物向猎物注射毒素以使其失去能力。其中一些毒素通过改变被称为离子通道的蛋白质的活性来发挥作用，离子通道存在于细胞膜中。这些通道可以允许钾离子和/或其他离子通过膜，并具有许多重要的作用。例如，离子通道参与心肌收缩，并允许信息在脑细胞之间传递。研究人员使用其中一些毒素作为工具来研究离子通道蛋白是如何工作的。例如，由狼蛛产生的一种名为沙莫毒素的毒素与一种名为酸敏离子通道(ASIC)的离子通道相结合。研究人员此前已经能够可视化附着在ASIC上的棉铃虫毒素的三维结构，这揭示了毒素如何与离子通道结合并改变其活性。另一种名为广喜毒素的狼蛛毒素与狼毒非常相似，但它与一种不同类型的钾离子通道结合。据认为，广西毒毒素结合在这些离子通道上的一个位置，位于膜的深处，但目前还不清楚这是如何发挥作用的。在这里，古普塔，扎马尼安，贝等人。比较这两种毒素的一些结构和化学性质。实验表明，这两种毒素都与膜相互作用，使它们能够与目标离子通道结合。然而，广西毒素进入膜的内部更深。此外，古普塔、扎马尼安、裴德亮等人的发现表明，这两种毒素都使用向内弯曲的相似表面来夹住它们的目标离子通道。这种共同的结构特征将有助于设计实验，以可视化结合到钾离子通道上的广西毒素的三维结构。DOI：http://dx.doi.org/10.7554/eLife.06774.002
Tarantula toxins that bind to voltage-sensing domains of voltage-activated ion channels are thought to partition into the membrane and bind to the channel within the bilayer. While no structures of a voltage-sensor toxin bound to a channel have been solved, a structural homolog, psalmotoxin (PcTx1), was recently crystalized in complex with the extracellular domain of an acid sensing ion channel (ASIC). In the present study we use spectroscopic, biophysical and computational approaches to compare membrane interaction properties and channel binding surfaces of PcTx1 with the voltage-sensor toxin guangxitoxin (GxTx-1E). Our results show that both types of tarantula toxins interact with membranes, but that voltage-sensor toxins partition deeper into the bilayer. In addition, our results suggest that tarantula toxins have evolved a similar concave surface for clamping onto α-helices that is effective in aqueous or lipidic physical environments. DOI: http://dx.doi.org/10.7554/eLife.06774.001 Venomous animals like tarantulas or scorpions inject their prey with toxins to disable them. Some of these toxins work by altering the activity of proteins called ion channels, which are found within membranes in cells. These channels can allow potassium ions and/or other ions to pass through the membrane and have many important roles. For example, ion channels are involved in heart muscle contraction and allow information to travel between brain cells. Researchers have used some of the toxins as tools to study how ion channel proteins operate. For example, a toxin produced by tarantulas called psalmotoxin binds to a type of ion channel called the acid-sensing ion channels (ASIC). Researchers have previously been able to visualize the three-dimensional structure of psalmotoxin attached to ASIC, which revealed how the toxin binds to and alters the activity of the ion channel. Another tarantula toxin called guangxitoxin is very similar to psalmotoxin, but it binds to a different type of potassium ion channel. It is thought that guangxitoxin binds to a site on these ion channels that is deep within the membrane, but it is not clear how this works. Here, Gupta, Zamanian, Bae et al. compare some of the structural and chemical properties of the two toxins. The experiments show that both toxins interact with the membrane to enable them to bind with their target ion channels. However, guangxitoxin moves deeper into the interior of the membrane. Also, Gupta, Zamanian, Bae et al.'s findings suggest that both toxins use a similar surface that curves inwards to clamp onto their target ion channels. This common structural feature will be useful for designing experiments to visualize the three-dimensional structure of guangxitoxin bound to a potassium ion channel. DOI: http://dx.doi.org/10.7554/eLife.06774.002