Gupta Kanchan, Zamanian Maryam, Bae Chanhyung, Milescu Mirela, Krepkiy Dmitriy, Tilley Drew C, Sack Jon T, Yarov-Yarovoy Vladimir, Kim Jae Il, Swartz Kenton J
Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institutes of Health, Bethesda, United States.
Department of Physiology and Membrane Biology, University of California, Davis, Davis, United States.
Elife. 2015 May 7;4:e06774. doi: 10.7554/eLife.06774.
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.
据认为，与电压激活离子通道的电压感应结构域结合的狼蛛毒素会分配到膜中，并与双分子层内的通道结合。虽然尚未解析出与通道结合的电压传感器毒素的结构，但一种结构同源物——圣歌毒素（PcTx1），最近与酸敏感离子通道（ASIC）的细胞外结构域形成复合物并结晶。在本研究中，我们使用光谱学、生物物理学和计算方法来比较PcTx1与电压传感器毒素广西毒素（GxTx-1E）的膜相互作用特性和通道结合表面。我们的结果表明，这两种类型的狼蛛毒素都与膜相互作用，但电压传感器毒素更深地分配到双分子层中。此外，我们的结果表明，狼蛛毒素已经进化出一个类似的凹面来夹在α螺旋上，这在水性或脂质物理环境中是有效的。
